leptin and Kidney-Failure--Chronic

Obesity and diabetes are major causes of CKD and ESRD, and are thus enormous health concerns worldwide. Both obesity and diabetes, along with other elements of the metabolic syndrome including hypertension, are highly interrelated and contribute to the development and progression of renal disease. Studies show that multiple factors act in concert to initially cause renal vasodilation, glomerular hyperfiltration, and albuminuria, leading to the development of glomerulopathy. The coexistence of hypertension contributes to the disease progression, which, if not treated, may lead to ESRD. Although early intervention and management of body weight, hyperglycemia, and hypertension are imperative, novel therapeutic approaches are also necessary to reduce the high morbidity and mortality associated with both obesity-related and diabetes-related renal disease.

Topics: Adiponectin; Animals; Cardiovascular Diseases; Cytokines; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Early Medical Intervention; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Leptin; Medication Therapy Management; Mice; Models, Animal; Obesity; Risk Reduction Behavior

Anorexia is a common complication in patients with chronic kidney disease (CKD) and is associated with the development of malnutrition and an increased risk of mortality. Several compounds are linked to anorexia in these patients; however, the mechanisms are unknown. Zinc (Zn) deficiency is associated with decreased food intake and has been observed in CKD patients. In addition, leptin is an anorexigenic peptide, and patients with CKD present generally high levels of this hormone. Studies have suggested an association between Zn and leptin status in human and rats; however, the results are inconsistent. Some claimed that Zn supplementation does not change leptin release or that there is no significant relationship between Zn and leptin. Others have reported that Zn might be a mediator of leptin production. CKD patients have hyperleptinemia and hypozincemia, but the relationship between Zn deficiency and leptin levels in CKD patients has been poorly understood until now. The aim of this review is to integrate knowledge on leptin and Zn actions to provide a cohesive clinical perspective regarding their interactions in CKD patients.

Topics: Animals; Anorexia; Eating; Humans; Kidney Failure, Chronic; Leptin; Malnutrition; Rats; Zinc

Chronic uremia is often characterized by wasting of muscle and fat mass, which has been defined as protein-energy wasting (PEW), and is responsible for substantial worsening of patient outcome in terms of morbidity and mortality, mostly from cardiovascular events. Despite major advances in patient treatment, nutritional outcome in patients with end-stage renal disease has not improved substantially in recent years. Extensive research in this field has provided plausible explanations for this limitation by indicating that the pathogenesis of PEW in kidney disease is complex and multifactorial. Complexity involves underlying metabolic alterations, including inflammation, oxidative stress, and insulin resistance. In addition, patient heterogeneity is increasing with large numbers of obese individuals as a result of the ongoing obesity epidemics. Several tissues are involved in cross-talk and contribute to metabolic derangements, including adipose tissue, the gut, and the central nervous system, with novel mediators including the gastric hormone ghrelin. Acknowledging its complex pathogenesis may favor the development of novel and more effective therapeutic tools for PEW. These should ideally be effective in treating the underlying common mechanisms of wasting, which appear to include oxidative stress, inflammation, and insulin resistance.

Topics: Animals; Ghrelin; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Obesity; Oxidative Stress; Protein-Energy Malnutrition

Experimental and clinical evidence implicates the 2 major adipose tissue cytokines, adiponectin (ADPN) and leptin (LEP), in renal damage. The interpretation of the link between these cytokines and renal outcomes is strictly context-sensitive. Albuminuria is a feature of renal disease in the ADPN null mouse and this alteration can be reversed by supplementing ADPN. Accordingly, in young normoalbuminuric obese individuals low ADPN is associated with higher albumin excretion rate. Conversely, high ADPN is associated with more severe proteinuria in chronic kidney disease patients, possibly underlying a protective response aimed at countering the high renal and cardiovascular risk of high proteinuria. LEP administration ameliorates insulin resistance in insulin-resistant patients with hereditary lipodystrophy--a disease characterized by severe LEP deficiency and renal disease--and the same intervention reverses both, insulin resistance and renal damage in a mouse model of LEP deficiency. However, LEP may exert noxious effects on the kidney (particularly renal fibrosis) if administered in conditions of LEP sufficiency or excess.

Topics: Adiponectin; Animals; Biomarkers; Disease Models, Animal; Humans; Kidney Failure, Chronic; Leptin; Mice; Rats; Risk Factors

Chronic inflammation is associated with cachexia and increased mortality risk in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Inflammation suppresses appetite and causes the loss of protein stores. In CKD patients, increased serum levels of pro-inflammatory cytokines may be caused by reduced renal function, volume overload, oxidative or carbonyl stress, decreased levels of antioxidants, increased susceptibility to infection in uremia, and the presence of comorbid conditions. Cachexia is brought about by the synergistic combination of a dramatic decrease in appetite and an increase in the catabolism of fat and lean body mass. Pro-inflammatory cytokines act on the central nervous system to alter appetite and energy metabolism and to provide a signal-through the nuclear factor-kappaB and ATP-ubiquitin-dependent proteolytic pathways-that causes muscle wasting. Further research into the molecular pathways leading to inflammation and cachexia may lead to novel therapeutic therapies for this devastating and potentially fatal complication of chronic disease.

Topics: Cachexia; Cardiovascular Diseases; Chronic Disease; Cytokines; Feeding and Eating Disorders; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Muscular Atrophy; Neuropeptides

Leptin is an adipocyte-derived hormone that acts as a major regulator of food intake and energy homeostasis. It circulates both as a free and as a protein-bound entity. Leptin is released into the blood in proportion to the amount of body fat and exerts sustained inhibitory effects on food intake while increasing energy expenditure. The leptin receptor belongs to the class I cytokine receptor superfamily and possesses strong homology to the signal-transducing subunits of the IL-6 receptor. The hypothalamic melanocortin system, and specifically the melanocortin-4 receptor (MC-4R), is critical in mediating leptin's effect on appetite and metabolism. Serum leptin concentrations are elevated in patients with chronic kidney disease (CKD) and correlate with C-reactive protein levels suggesting that inflammation is an important factor that contributes to hyperleptinemia in CKD. Hyperleptinemia may be important in the pathogenesis of inflammation-associated cachexia in CKD. We showed that experimental uremic cachexia was attenuated in db/db mice, a model of leptin receptor deficiency. Nephrectomy in these animals did not result in any change in weight gain, body composition, resting metabolic rate, and efficiency of food consumption. Furthermore, experimental uremic cachexia could be ameliorated by blocking leptin signaling through the hypothalamic MC-4R. MC-4R knockout mice or mice administered the MC-4R and MC-3R antagonist, agouti-related peptide, resisted uremia-induced loss of lean body mass and maintained normal basal metabolic rates. Thus, melanocortin receptor antagonism may provide a novel therapeutic strategy for inflammation-associated cachexia in CKD.

Topics: Animals; Appetite; Cachexia; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Melanocyte-Stimulating Hormones; Mice; Receptors, Cell Surface; Receptors, Leptin; Receptors, Melanocortin; Signal Transduction

Enhanced chronic systemic inflammation and reduced insulin sensitivity are often associated in patients with chronic renal failure, contributing to cardiovascular morbidity and mortality in these patients. Adipose tissue produces several hormones (adipocytokines including leptin, resistin, tumor necrosis factor-alpha, and adiponectin) that modulate both systemic inflammatory response and insulin action. High leptin, resistin, and tumor necrosis factor-alpha and low adiponectin are associated with proinflammatory conditions, whereas opposite patterns are commonly observed in the presence of increased insulin sensitivity, low inflammation, and reduced cardiovascular risk. Oxidative stress has also been shown recently to modulate adipocytokine production, resulting in a proinflammatory profile. Increments of plasma concentrations of both proinflammatory and anti-inflammatory adipocytokines have been reported in chronic renal failure, possibly caused by both passive accumulation from reduced renal excretion and metabolic abnormalities induced by uremia. The potential role of altered adipose tissue adipocytokine production in the onset of renal failure-associated inflammatory and metabolic derangements remains largely to be elucidated and is discussed in the current report.

Topics: Adiponectin; Adipose Tissue; Cytokines; Ghrelin; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Nutritional Physiological Phenomena; Oxidative Stress; Peptide Hormones; Uremia

From an evolutionary perspective, Darwinian selection has favored insulin-resistant individuals, ie, those with a trait ensuring brain functioning in situations of extreme fuel deprivation. The ability to mount a powerful inflammatory response to infection was another survival advantage in our ancestors, and we now have solid evidence showing that these 2 traits, insulin resistance and inflammation (as measured by serum C-reactive protein [CRP]), are associated in modern human beings. In an analysis of 192 nondiabetic hemodialysis patients, leptin and adiponectin were related in an opposite fashion with insulin sensitivity in end-stage renal disease (ESRD) and interacted in determining insulin resistance in these patients. The risk of insulin resistance was about 6 times higher in ESRD patients with an unfavorable combination of the 2 adipokines (high leptin and low adiponectin) than in those with a favorable combination (low leptin and high adiponectin). Low adiponectin but not high leptin predicted incident cardiovascular events in this cohort. Neither leptin nor adiponectin were associated with CRP in a cross-sectional analysis, but they were linked in an opposite fashion to CRP in a longitudinal study in 21 patients with acute inflammation secondary to infection. High sympathetic activity predicts adverse cardiovascular outcomes in ESRD. Of note, we found that the risk for cardiovascular events is more than 3 times higher in patients with high sympathetic activity and low adiponectin than in those with high adiponectin and low sympathetic activity. The adipocyte hormones leptin and adiponectin are associated in an opposite fashion to insulin sensitivity and inflammation in ESRD patients. Relatively lower plasma adiponectin levels are associated with a higher rate of incident cardiovascular events. Finally, low adiponectin and high norepinephrine seem to be interacting factors in the dismal cardiovascular outcomes with ESRD.

Topics: Adiponectin; Adipose Tissue; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Cytokines; Energy Metabolism; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Leptin; Renal Dialysis; Risk Factors

An activated inflammatory response is a common feature of end-stage renal disease (ESRD) patients and predicts outcome. Although various factors related to the dialysis procedure may contribute to inflammation in ESRD, a number of nondialysis-related factors also are of importance. Adipose tissue is a complex organ with functions far beyond the mere storage of energy and secretes a number of proinflammatory adipokines, such as leptin, resistin, tumor necrosis factor-alpha and interleukin-6, as well as one anti-inflammatory adipokine, adiponectin. It has been proposed that adipose tissue may be a significant contributor to increased systemic inflammation in nonrenal patients. In this review, we put forward the hypothesis that a reduction of renal mass will contribute to retention of proinflammatory adipokines, thus generating adipokine imbalance. Such an imbalance may, via effects on the central nervous system and the vasculature, contribute to wasting, atherosclerosis, and insulin resistance--all common features of ESRD.

Topics: Adiponectin; Adipose Tissue; Body Composition; Body Mass Index; Cardiovascular Diseases; Cytokines; Humans; Infections; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Obesity; Renal Dialysis; Resistin; Risk Factors; Tumor Necrosis Factor-alpha; Wasting Syndrome

Malnutrition is defined as abnormalities caused by an inadequate diet, but this term is often used inappropriately to describe the syndrome of loss of body weight with muscle mass being replaced by fatty tissue and declining serum proteins present in adults and children with chronic kidney disease (CKD). This syndrome is more accurately described as cachexia, and manifests as growth failure in children with CKD. Cachexia is common and is an important risk factor for poor quality of life and increased mortality and morbidity in both adults and children with CKD. Anorexia, acidosis and inflammation are important causes of cachexia, but the underlying molecular mechanism is not well understood. Dietary intake is often poor and resting metabolic rate is increased in CKD. The energy cost of growth is increased in experimental CKD. Circulating concentrations of cytokines, such as leptin, tumor necrosis factor-alpha and interleukins 1 and 6 are increased in patients with CKD and correlate with the degree of cachexia in these individuals. We hypothesize that cytokines signal through orexigenic neuropetides such as agouti-related peptide and neuropeptide Y (NPY), and anorexigenic neuropetides such as proopiomelanocortin and alpha-melanocyte-stimulating hormone in the arcuate nucleus in the hypothalamus. This signaling system also involves the NPY receptor and the melanocortin receptors and controls appetite and metabolic rate in health and disease. Furthermore, the first order neurons of this system are located outside the blood-brain barrier and can therefore sense the circulating levels of cytokines, as well as long-term satiety hormones such as leptin and insulin and short-term satiety hormones such as ghrelin and peptide (P) YY. There is experimental evidence that this hypothalamic neuropeptide signaling system may have an important role in the pathogenesis of cachexia in CKD. Understanding the molecular mechanism of cachexia in CKD may lead to novel therapeutic strategies.

Topics: Cachexia; Child; Chronic Disease; Cytokines; Ghrelin; Humans; Kidney Diseases; Kidney Failure, Chronic; Leptin; Malnutrition; Peptide Hormones

The hypothesis that alterations of serum concentrations of the anorexigenic adipose tissue-derived hormone leptin or the orexigenic peptide ghrelin might help to regain appetite and fight malnutrition in patients with chronic renal failure cannot be confirmed at present. For the future, however, strategies interfering with signal transduction of these peptides in the hypothalamus might be more promising and should be investigated and further developed.

Topics: Appetite; Disease Progression; Ghrelin; Humans; Kidney Diseases; Kidney Failure, Chronic; Leptin; Osmolar Concentration; Peptide Hormones; Uremia

Risks of chronic metabolic acidosis in patients with chronic kidney disease. Metabolic acidosis is associated with chronic renal failure (CRF). Often, maintenance dialysis therapies are not able to reverse this condition. The major systemic consequences of chronic metabolic acidosis are increased protein catabolism, decreased protein synthesis, and a negative protein balance that improves after bicarbonate supplementation. Metabolic acidosis also induces insulin resistance and a decrease in the elevated serum leptin levels associated with CRF. These three factors may promote protein catabolism in maintenance dialysis patients. Available data suggest that metabolic acidosis is both catabolic and anti-anabolic. Several clinical studies have shown that correction of metabolic acidosis in maintenance dialysis patients is associated with modest improvements in nutritional status. Preliminary evidence indicates that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Interventional studies for metabolic acidosis have yielded inconsistent results in CRF and maintenance hemodialysis patients. In chronic peritoneal dialysis patients, the mitigation of acidemia appears more consistently to improve nutritional status and reduce hospitalizations. Large-scale, prospective, randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in maintenance hemodialysis patients. To avoid adverse events, an aggressive management approach is necessary to correct metabolic acidosis. Clinicians should attempt to adhere to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines for maintenance dialysis patients. The guidelines recommend maintenance of serum bicarbonate levels at 22 mEq/L or greater.

Topics: Acidosis; Amino Acids, Branched-Chain; Animals; Firefly Luciferin; Humans; Hydrocortisone; Hyperparathyroidism, Secondary; Insulin Resistance; Kidney Failure, Chronic; Leptin; Luciferases; Nutritional Status; Rats

Topics: Carnitine; Cytokines; Dialysis; Energy Intake; Humans; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Malnutrition; Nutrition Therapy

Topics: Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Renal Replacement Therapy

Adipose tissue is a necessary survival characteristic of species that do not have constant access to food. TNF-alpha is a very fundamental "internal regulator" (intra-system) of adipose tissue metabolism, and IL-6 and IL-1 beta are relevant control factors, as well. Leptin and IL-6, but not TNF-alpha, appear to be the major signals linking adipose tissue to the systemic immunologic response. In ESRD, it has been coherently observed that acute-phase reactants like CRP and serum amyloid A are independently associated to atherosclerosis, death, and cardiovascular complications. Leptin is inversely related with plasma creatinine, suggesting that reduced renal clearance is a primary factor responsible for hyperleptinemia in ESRD. On the other hand, this adipose tissue hormone behaves as an inverse acute-phase reactant (i.e., it decreases during spontaneous episodes of the acute-phase response). Dialysis patients with hyperleptinemia have more severe degrees of insulin resistance but further studies are required to see whether leptin plays a role in insulin resistance in these patients. The most abundant protein synthesized in the adipose tissue, adiponectin, is inversely related to metabolic risk factors like glucose, triglycerides, insulin, and HDL cholesterol in uremic patients, suggesting that this cytokine is a protective factor for the cardiovascular system. Accordingly, plasma adiponectin is an independent, inverse predictor of incident cardiovascular events in dialysis patients.

Topics: Adiponectin; Adipose Tissue; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Kidney Failure, Chronic; Leptin; Proteins

Topics: Aldosterone; Calcitriol; Endocrine System Diseases; Erythropoietin; Hormones; Human Growth Hormone; Humans; Kidney Failure, Chronic; Leptin; Parathyroid Hormone

Protein-energy malnutrition is a major comorbid condition in persons with renal disease. A variety of interventions have been implemented to supplement protein and energy intake in malnourished patients with renal disease, but the prevalence of protein-energy malnutrition remains high. Leptin, a hormone secreted by adipose tissue, decreases food intake via neuroendocrine systems in the hypothalamus in persons with normal renal function. Serum leptin levels are elevated in patients with chronic renal insufficiency and end-stage renal disease, and experimental evidence suggests a possible role for leptin in the development of protein-energy malnutrition in this population. Release of leptin from adipocytes may be stimulated by cytokines mediating the inflammatory response, which is frequently pronounced in patients with end-stage renal disease receiving hemodialysis and peritoneal dialysis. This article provides an overview of research conducted on serum leptin levels in different stages of renal disease, and the relationship among serum leptin, body composition, biochemical indexes, and markers of inflammation in persons with end-stage renal disease. Effects of intradialytic parenteral nutrition and anabolic factors on leptin levels and nutritional status are briefly reviewed.

Topics: Cytokines; Energy Intake; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Nutritional Status; Peritoneal Dialysis; Prevalence; Protein-Energy Malnutrition; Renal Dialysis

Topics: Humans; Kidney Failure, Chronic; Leptin

Leptin, an adipocyte-derived hormone, signals to the brain information on the amount of energy stored in adipose tissue and regulates energy homeostasis. In addition, leptin has been implicated in the regulation of neuroendocrine function, growth, hematopoiesis, and immune regulation. Plasma leptin is cleared by the kidney, and thus, leptin levels are elevated in hemodialysis patients. Whether the elevated leptin levels in hemodialysis patients contribute to the pathophysiology of the clinical manifestations of renal failure in humans remains to be conclusively shown in the future.

Topics: Carrier Proteins; Humans; Kidney; Kidney Failure, Chronic; Leptin; Proteins; Receptors, Cell Surface; Receptors, Leptin; Renal Dialysis

Mutation of the Ob gene, which encodes for leptin, or mutation of the leptin receptor leads to obesity in mice. Humans, for the most part, have a positive correlation of leptin with body fat mass suggesting possible defects in leptin effector mechanisms that may contribute to obesity. As patients on hemodialysis have difficulty with appetite, we investigated whether leptin is cleared by the kidney and is elevated in hemodialysis patients. In patients with intact renal function there was a net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there was no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal disease (ESRD), peripheral leptin levels factored for body mass index was increased by fourfold as compared to a group of healthy controls (N = 338). The leptin receptor exists in a long and short form, with the long form primarily expressed in the hypothalamus but also in the lungs and kidneys of the mouse. Further studies are necessary to clarify the role of leptin in regulating appetite in patients with ESRD and the role of leptin in directly affecting kidney function via its receptors.

Topics: Animals; Carrier Proteins; Humans; Kidney; Kidney Failure, Chronic; Leptin; Proteins; Receptors, Cell Surface; Receptors, Leptin

Topics: Humans; Kidney Failure, Chronic; Leptin; Nephrology; Proteins

Insulin resistance (IR), a risk factor for cardiovascular disease and all-cause mortality, is prevalent among maintenance hemodialysis patients. Effects of omega-3 fatty acids on IR in hemodialysis patients have not been well understood. This study aimed to determine the effects of omega-3 fatty acids on IR and serum lipids of hemodialysis patients.. Fifty-four adult patients on hemodialysis were randomly assigned to receive either 1800 mg of omega-3 fatty acids or placebo daily for 4 months. Serum concentrations of glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, insulin, leptin, and adiponectin were measured at baseline and after 4 months of the intervention. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance and 2 adipokine-based measures of IR, including the leptin-adiponectin ratio and homeostasis model assessment corrected by adiponectin.. Mean differences of serum C-reactive protein, insulin, leptin, and adiponectin concentrations did not show significant difference between the two groups following 4 months of intervention. Fasting serum glucose and low-density lipoprotein cholesterol were not significantly influenced by omega-3 supplementation, either. Serum triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels significantly decreased in the omega-3 group (P = .02, P = .03, and P < .001, respectively). None of the indirect indexes of IR showed significant changes at the end of the study in either the omega-3 or placebo group.. Supplemental use of omega-3 fatty acids showed some beneficial effects on lipid profile of hemodialysis patients without any improvement in IR.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Blood Urea Nitrogen; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Dietary Supplements; Docosahexaenoic Acids; Eicosapentaenoic Acid; Female; Humans; Insulin; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Single-Blind Method; Treatment Outcome; Triglycerides

Diabetic Nephropathy (DN) is one of the main complications of diabetes mellitus, mostly ending to end-stage renal disease. Leptin and C-reactive protein (CRP), as inflammatory markers implicated in the progression of DN, increase in diabetes mellitus, while transferrin and albumin, as members of anti-oxidant defense mechanism, are found to decline.. In a controlled clinical trial, 65 patients with type 2 DN were assigned to receive lovastatin or placebo, for 3 months, to assess statins' impact on serum levels of leptin, CRP, transferrin, albumin, and lipid profile.. Serum levels of CRP (3.52 +/- 4.16 mg/dL to 2.84 +/- 3.06 mg/dL, P = .02), leptin (10.78 +/- 8.30 mg/dL to 7.80 +/- 5.41 mg/dL, P = .006), low-density lipoprotein cholesterol (116.16 +/- 46.54 mg/dL to 85.46 +/- 29.22 mg/dL, P = .001), and total cholesterol (199.00 +/- 43.33 mg/dL to 164.67 +/- 35.19 mg/dL, P = .001) were lowered after lovastatin therapy. Mean serum level of high-density lipoprotein cholesterol increased (40.00 mg/dL to 42.80 mg/dL, P = .005) after the treatment. Lovastatin had no significant effect on albumin and transferrin. Placebo did not change any of the parameters after 3 months.. The effect of statins on the inflammatory markers involved in the development of DN is a new approach to evidence supporting the pleiotropic effect of this drug group.

Topics: Adult; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Failure, Chronic; Leptin; Lovastatin; Male; Middle Aged

Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity.. This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects.. At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored.. Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63 × 10(-3) to 0.76 × 10(-3). This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP.. Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation.. ClinicalTrial.gov NCT01253928.

Topics: Adipokines; Adipose Tissue; Adult; Body Composition; Cross-Over Studies; Double-Blind Method; Fasting; Female; Glucose; Homeostasis; Humans; Insulin Resistance; Intra-Abdominal Fat; Kidney Failure, Chronic; Leptin; Liver; Male; Middle Aged; Pilot Projects; Pioglitazone; Renal Dialysis; Subcutaneous Fat; Thiazolidinediones

Protein-energy malnutrition is still a problem in patients with chronic renal failure, especially during replacement renal therapy. The chronic inflammatory status in these patients intensifies the malnutrition, as well as making treatment more complicated. The aim of the present study was to estimate the influence of oral supplementation on the nutritional status of malnourished hemodialysis (HD) patients depending on the existence of an inflammatory state.. To study the influence of oral supplementation on nutrition status, 30 HD patients with protein-energy malnutrition characteristics and 25 well-nourished HD patients were enrolled in the study. Malnourished HD patients were prescribed Renilon 7.5 at an oral intake dose of 125 mL twice a day for 3 months. The nutritional status was characterized based on body mass index, Subjective Global Assessment score, serum albumin and prealbumin concentrations. The intensity of the inflammatory state was determined by C-reactive protein and interleukin-6. Serum concentrations of leptin and adiponectin were also measured.. After 3 months of supplementation, malnourished patients had an increase in prealbumin, albumin, and leptin concentrations. No statistically significant differences were observed between patients lacking inflammation and those with inflammation.. The results indicate an improvement in the nutritional status of HD patients who were prescribed an oral supplementation. Furthermore, patients with inflammatory state characteristics also benefited from Renilon 7.5 treatment.

Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Dietary Supplements; Female; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin

Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). A few studies have demonstrated elevated plasma adiponectin and leptin levels in CKD. The aims of this study were to assess whether 1) estimated glomerular filtration rate (eGFR) is associated with plasma leptin and adiponectin; and 2) adiponectin and leptin (partly) explain associations of CKD with endothelial dysfunction, insulin resistance, and low-grade inflammation in patients with K/DOQI Stage 3 - 5 CKD.. Baseline data from 91 patients with Stage 3 - 4 CKD in the anti-oxidant therapy in chronic renal insufficiency study, a randomized, double-blind, placebo-controlled trial, in which the effects of oxidative stress-lowering treatment on vascular function and structure were studied, and from 50 dialysis naïve patients, who took part in an open-label, randomized study that compared two peritoneal dialysis regimens, used in the analysis. All subjects for both the studies were recruited in the same centres.. The association between eGFR and adiponectin was non-linear. In multivariate analysis, log-eGFR (unstandardized beta = 8.303 microg/ml, p < 0.0001) was the strongest determinant of adiponectin, and body mass index the strongest determinant of leptin (beta = 2.477 ng/ml, p < 0.0001). Plasma adiponectin and leptin did not modify the associations between eGFR and plasma von Willebrand factor or soluble vascular adhesion molecule-1. Plasma leptin had the strongest association with the homeostatic model assessment (HOMA-IR) index. Plasma C-reactive protein had no association with adiponectin or leptin.. In patients with K/DOQI Stage 3 - 5 CKD, renal function had a significant non-linear inverse association with and was the strongest predictor of adiponectin. BMI was the strongest predictor of plasma leptin. Plasma adiponectin and leptin did not explain, and thus presumably are not involved in, the association between eGFR and some markers of endothelial dysfunction.

Topics: Adiponectin; Antioxidants; Body Mass Index; Cross-Sectional Studies; Double-Blind Method; Female; Glomerular Filtration Rate; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Kidney Function Tests; Leptin; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis; von Willebrand Factor

Leptin is a middle-molecular weight uremic toxin. Hemodiafiltration with on-line endogenous reinfusion (HFR) is a novel dialytic method combining the processes of diffusion, convection and adsorption. We performed a prospective crossover study of patients with end-stage renal disease to investigate the effect of HFR therapy on the level of leptin as compared to conventional low flux hemodialysis (LHD).. Eleven stable hemodialysis patients were treated with LHD for 12 weeks and then treated with HFR (SG30 Plus; Sorin Group Italia S.r.1, Mirandola, Italy) for 12 weeks.. After 12 weeks of HFR treatment, serum leptin levels significantly decreased (17.1 (2.66 - 39.5) at Week 12 vs. 12.3 (1.80 - 24.3) ng/ml at Week 24, p = 0.014). Although serum adiponectin levels also decreased (1.66 (1.44 - 1.86) at Week 12 vs. 1.12 (0.79 - 1.34) g/ml at Week 24, p = 0.001), the ratio of leptin to adiponectin did not increase after HFR treatment. Serum beta2-microglobulin (beta2M) levels significantly decreased (37.7 (29.8 - 42.6) at Week 12 vs. 28.3 (26.5 - 32.2) mg/dl at Week 24, p = 0.002). Dry weight, Kt/V(urea), normalized protein equivalent of nitrogen appearance, subjective global assessment, and serum albumin levels of the patients were not changed after HFR treatment. There was no difference in the serum levels of C-reactive protein or interleukin-6 between Week 12 and Week 24.. The results of our study indicate that HFR may be a better therapy than LHD for removal of middle-molecular-weight uremic toxins such as leptin and b2M.

Topics: Aged; Biomarkers; Cross-Over Studies; Female; Follow-Up Studies; Hemodiafiltration; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prospective Studies; Treatment Outcome

Leptin, secreted from adipose tissue, regulates food intake, energy expenditure, and immune function. It is unknown whether leptin predicts mortality in patients with chronic kidney disease stage 5 on hemodialysis therapy.. We performed a prospective cohort study of 71 patients with chronic kidney disease stage 5 in an outpatient hemodialysis center. Subjects were recruited in June 1998 and followed for 83 months. Survival was compared by the Kaplan-Meier method.. After 83 months of follow-up, 48 patients (68%) had died. Serum leptin concentrations at study entry were lower among all deceased patients compared with those patients who survived (5.2 +/- 9.0 microg/L; n = 48; vs. 7.7 +/- 7.8 microg/L; n = 23; p = 0.005). Baseline serum leptin concentrations were significantly lower in patients who died from cardiovascular diseases (4.7 +/- 9.4 microg/L, n = 32) or infections (4.0 +/- 2.7 microg/L; n = 10; each p < 0.05), but not cancer (9.4 +/- 7.9 microg/L; n = 6), than in survivors (7.7 +/- 7.8 microg/L; n = 23; p = 0.003). The relative risk for mortality in patients with serum leptin concentrations below the median (<2.6 microg/L) compared with patients above the median was 1.96 (95% confidence interval, 1.01 to 3.79; p = 0.04). Survival was shorter in patients with leptin concentrations below the median compared with those whose leptin concentrations were above the median (all-cause mortality, chi(2) = 5.05; p = 0.02).. Low serum leptin concentration is an independent predictor of mortality in patients with chronic kidney disease stage 5 on hemodialysis therapy.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prognosis; Renal Dialysis; Survival Analysis

Dialysis patients with a high body mass index are less likely to experience severe anemia. Leptin, a hormone secreted by adipocytes, may have a role in protecting against renal anemia. The aim of the present study is to determine the effect of an increase in serum leptin levels by increasing energy intake on recombinant human erythropoietin (rHuEPO) response in long-term hemodialysis (HD) patients.. We enrolled 65 long-term HD patients to explore the association between leptin level and rHuEPO response by classifying them as either high- or low-leptin individuals (phase 1). Thereafter, 39 patients with malnutrition by means of Subjective Global Assessment were randomly assigned to high-energy and high-protein (an extra 475 kcal and 16.6 g of protein daily; group A; n = 12) or standard-energy, but high-protein (an extra 67.2 kcal and 16.8 g of protein daily; group B; n = 27), supplementation for 12 weeks. Serial serum leptin levels, nutritional measures, and hematologic parameters were obtained. Age- and sex-matched well-nourished patients (group C; n = 16) not administered extra nutritional supplementation served as control subjects (phase 2).. In phase 1, a significantly lower erythropoietin dose, greater hematocrit, and better nutritional measures were observed in the high-leptin group (P < 0.001). In phase 2, there was a significant increase in body fat mass (P = 0.001) and median serum leptin levels (P < 0.001) in response to 12 weeks of high-energy supplementation in group A, accompanied by markedly improved erythropoiesis (P < 0.05) compared with groups B and C.. Hyperleptinemia reflects better nutritional status and rHuEPO response in long-term HD patients. Increasing energy intake improves erythropoiesis, which may be mediated in part by an increase in serum leptin levels.

Topics: Adipose Tissue; Aged; Anemia; Body Composition; Cross-Sectional Studies; Dietary Proteins; Dietary Supplements; Drug Resistance; Energy Intake; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prospective Studies; Protein-Energy Malnutrition; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Malnutrition-inflammation complex syndrome and anorexia, common conditions in maintenance dialysis patients, are strongly associated with higher mortality and hospitalization and lower quality of life (QoL) in this population. Megestrol acetate, 800 mg/day, has been shown to increase appetite and food intake and to mitigate inflammation in cachectic AIDS and cancer patients, leading to weight gain, but it is also associated with side effects at this dose.. We evaluated the efficacy of the oral solution of megestrol acetate in half of its conventional dose in improving the nutritional state and inflammation in 10 hypoalbuminemic dialysis patients (albumin < 3.7 g/dL). Six women and 4 men, ages 60.2 years, took 400 mg of megestrol acetate solution daily for 16 weeks. Anthropometry, dual energy x-ray absorptiometry, 24-hour diet recalls, and biochemical measurements of nutrition and inflammation, including serum C-reactive protein and leptin, were performed.. At the end of the 16 weeks of intervention, weight and body mass index increased by 9%, body fat proportion by 31%, and triceps skinfold by 40% (P < .01). Serum albumin increased from 3.0 to 3.3 g/dL and continued to increase significantly to 3.6 g/dL after 3 months postintervention (P = .03). Serum leptin increased from 5.2 to 10.7 ng/mL (P = .09). Daily protein and energy intake increased progressively up to 27% to 42% by the end of the trial (P < or = .01). In 8 patients without acute infection, serum C-reactive protein declined from 1.24 to 0.78 mg/L (P = .06). QoL and appetite were reported to be improved. No major side effects were observed, and all 10 patients completed the 16 weeks of daily intake of megestrol acetate without interruption.. Megestrol acetate oral solution in half of its conventional dose is safe and improves the nutritional state, inflammation, and anorexia in maintenance dialysis patients. Larger-scale placebo-controlled randomized studies are needed to confirm the beneficial effects of 400 mg/day of megestrol acetate in dialysis patients.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Anthropometry; Body Composition; Body Mass Index; Body Weight; C-Reactive Protein; Dietary Proteins; Energy Intake; Female; Humans; Hypoalbuminemia; Inflammation; Kidney Failure, Chronic; Leptin; Male; Megestrol Acetate; Middle Aged; Nutritional Status; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Syndrome; Treatment Outcome

Chronic renal failure (CRF) is associated with increased plasma levels of ghrelin and leptin, but the regulation of the secretion of these hormones has been insufficiently studied, in this setting. The aim of this study was to analyze the acute effects of oral feeding or intraperitoneal 3.86% glucose-based dialysate infusion on plasma ghrelin and leptin levels in patients with CRF undergoing peritoneal dialysis (PD).. Following a crossover design, 10 patients and eight healthy controls underwent a standardized oral intake, a 3.86% glucose-based dialysate PD exchange (patients) and placebo oral intake. We scrutinized acute changes in plasma ghrelin, leptin, glucose, insulin, and growth hormone (GH) levels.. In patients, total ghrelin decreased modestly immediately after oral feeding (nadir 90.6% of baseline, range 85.1, 94.5, P= 0.03) or the PD exchange test (92.2%, range 58.7, 101.9, P= 0.05) (median). Response to oral feeding was markedly blunted when compared with healthy individuals (73.8%, range 56.1, 89.1, P= 0.007) (P < 0.005 vs. patients). Plasma acyl-ghrelin had a less marked but more persistent decay after the PD exchange test (nadir 80.4%, range 55.1, 96.3, P= 0.02) than after oral intake (64.4%, range 45.6, 82.3, P= 0.005); again, changes were more intense in normal controls (47.4%, range 32.1, 67.3, P= 0.01) (P < 0.05 vs. patients). Leptin levels decreased slightly (P < 0.05) after the PD exchange in patients, but did not respond acutely to oral feeding in patients or controls.. Ghrelin secretion is partially refractory to the acute inhibitory effect of oral feeding in patients with CRF undergoing PD therapy. A 3.86% glucose-based PD exchange results in a significant decrease of plasma ghrelin levels. Plasma leptin levels are not acutely affected by oral feeding in patients with CRF or healthy individuals.

Topics: Acylation; Adult; Aged; Blood Glucose; Cross-Over Studies; Dialysis Solutions; Eating; Female; Ghrelin; Glucose Solution, Hypertonic; Human Growth Hormone; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peptide Hormones; Peritoneal Dialysis

Hyperleptinaemia in chronic haemodialysis (CHD) patients has been associated with malnutrition, which is an independent predictor of morbidity and mortality in this patient group.. To assess the influence of HD on plasma leptin, 10 CHD patients were crossover randomized to low-flux polysulfone (PS: F 6HPS), high-flux PS (F 60S), super-flux PS (F 500S) or super-flux cellulose-tri-acetate (CTA: Tricea 150G) for 12 weeks each. Blood samples were collected at the start of the study and each 12-week period. In addition, the relationship between patient characteristics, inflammation and leptin was analysed.. At baseline, all groups showed similar leptin concentrations (mean 33.6+/-21.7 ng/ml). After a single HD session, a significant (P<0.01) decrease was observed with all three high permeable devices (Tricea 150G -52.7+/-6.4%; F 60S -63.1+/-5.7%; F 500S -68.7+/-8.2%), whereas leptin remained stable with low-flux PS. After 12 weeks, a marked increase was observed with low-flux PS (week 1, 30.4+/-23.0; week 12, 40.5+/-5.4 ng/ml, P = 0.05), no change with super-flux CTA and high-flux PS (Tricea 150G week 1, 29.4+/-23.7; week 12, 32.0+/-27.9 ng/ml, P = ns; F 60S week 1, 36.0+/-31.8; week 12, 33.0+/-31.2 ng/ml, P = ns), and a significant decrease with super-flux PS (week 1, 38.3+/-33.0; week 12, 29.5+/-31.9 ng/ml, P = 0.02). The change in leptin after 12 weeks was significantly different between super-flux PS, and both low-flux PS (P = 0.009) and super-flux CTA (P = 0.01). Besides interleukin-6 (IL-6) at the start of the study (P = 0.006), no correlations were observed between patient characteristics, parameters of inflammation and plasma leptin levels.. Apart from low-flux PS, plasma leptin decreased considerably with all three high permeable dialysers after a single HD session. In the long run, leptin levels were lower with high-flux PS than with low-flux PS. Moreover, after switching from high-flux PS to super-flux PS (but not super-flux CTA), an additional decrease in leptin was observed. Apart from IL-6 at the start of the study, neither patient characteristics nor inflammatory parameters correlated with plasma leptin levels in this patient group.

Topics: Adult; Aged; Biocompatible Materials; C-Reactive Protein; Creatinine; Cross-Over Studies; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Membranes, Artificial; Middle Aged; Polymers; Renal Dialysis; Sulfones

Hyperleptinaemia is a well-known biochemical feature found in uraemic patients. However, little is known about the hormonal regulation of leptin in chronic renal disease. Recent studies have shown that circulating leptin levels are modified by treatment with recombinant human growth hormone (rhGH), by recombinant insulin-like growth factor I (rhIGF I), or by a combination of rhIGF I plus rhGH in patients with chronic renal failure. We performed a prospective study to assess plasma leptin concentrations in a group of dialysis patients both before and during short-term rhGH therapy.. We studied eight dialysis patients (four haemodialysis (HD) and four on continuous ambulatory peritoneal dialysis (CAPD); three female, five male; mean age 63.9 +/- 3.1 years). All patients were instructed to maintain a stable diet (35 kcal/kg/day and 1 g protein/kg/day ideal body weight) and were treated with rhGH (0.2 IU/kg/day s.c.) for 4 weeks. Blood samples were taken at 0, 2, 4, and 8 weeks for determination of leptin, GH, and IGF I. Serum insulin concentrations were assessed at 0 and 4 weeks.. Mean plasma leptin concentrations were elevated (36.2 +/- 12.8 ng/ml) at study outset and increased progressively throughout the 4 weeks of rhGH therapy (43.7 +/- 13.5 ng/ml (2 weeks, NS) and 70.6 +/- 18.4 ng/ml (4 weeks, P<0.0001)). These values returned to baseline levels (38.0 +/- 12.0 ng/ml, NS) at 1 month after rhGH withdrawal. rhGH therapy was accompanied by the development of direct correlations between leptin and IGF I concentrations at 2 weeks (r=0.86, P<0.01), and with correlations between leptin and IGF I (r=0.84, P<0.01) and between leptin and insulin (r=0.88, P<0.01) after 4 weeks of rhGH administration.. These results confirm the presence of high circulating plasma leptin in dialysis patients and show that these levels are further increased by exogenous rhGH administration. The increase in plasma leptin after rhGH therapy may be related to the rhGH-induced changes in insulin in these patients.

Topics: Aged; Cross-Over Studies; Drug Administration Schedule; Female; Growth Hormone; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Osmolar Concentration; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies; Recombinant Proteins; Renal Dialysis

There are many growth factors (GFs), which stimulate the proliferation and maturation of erythroid progenitors. The main one is erythropoietin (Epo). Epo acts in concert with other GFs. Recently it was suggested that leptin (Lep) could be involved in a very early stage of erythropoiesis (E). The aim of this study was to analyse the relations between ability of idiopathic compensation of anemia by hemodialysis patients (HD pts) and concentration of Lep in HD men and women separately. The study was performed in 25/13M, 12F/HD pts, who idiopathically compensate anemia (group 1) and 29/16M, 13F/HD pts who required rHuEpo therapy (group 2). The mean Lep level in all women together was significantly higher than in all HD men together (26.9 +/- 6.3 ng/mL vs 6.8 +/- 0.9 ng/mL) but BMI was similar in men and women. We did not find significant differences in level of Lep in both studied groups of HD pts. Perhaps the lower influence of Epo and testosterone on E in HD women is compensated by significantly higher Lep concentration.

Topics: Adult; Anemia; Erythropoiesis; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

Leptin, the obese gene (ob) product, is a plasma protein synthesized exclusively in adipocytes and plays an important role in regulation of food intake and energy expenditure. The aim of the study was to compare serum leptin concentration in hemodialyzed (HD) patients and in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and to assess the relationship between leptinemia and parameters of nutritional state and inflammatory markers. We studied two group of patients with end-stage renal failure: 52 hemodialyzed individuals aged 24-74 years and 19 peritoneally dialyzed patients aged 20-70 years. Serum hemoglobin concentration, erythrocyte count, cholesterol, triglycerides, total protein, albumin, urea before and after HD, urea in CAPD patients, CRP, peritoneal protein loss were determined by standard laboratory methods. Serum leptin concentration before and after HD, in CAPD patients, leptin in ultrafiltrate and in peritoneal fluid was measured by commercially available radioimmunoassay. Plasma TNF-alpha and IL-1 concentration were measured by ELISA. We found that the serum leptin concentration was higher in hemodialyzed patients than in peritoneal dialyzed individuals (19.97 +/- 22.57 ng/mL vs 3.52 +/- 4.39 ng/mL, p < 0.01). There was a significant correlation between serum leptin levels and BMI in both studied groups (r = 0.81, p < 0.01 in HD group; r = 0.46, p < 0.05 in CAPD group). Concentrations of inflammatory markers (CRP, TNF-alpha, IL-1) were higher in hemodialyzed patients. Peritoneally dialyzed patients presented higher serum lipid concentrations (cholesterol and triglycerides) (p < 0.05). Neither inflammatory markers concentrations nor serum lipid concentrations correlate with the serum concentration of leptin.

Topics: Adult; Aged; Ascitic Fluid; Body Mass Index; Cholesterol; Humans; Interleukin-1; Kidney Failure, Chronic; Leptin; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Triglycerides; Tumor Necrosis Factor-alpha

Leptin, a recently discovered peptide involved in nutrient intake and energy expenditure, has been shown to be abnormally regulated in certain conditions such as obesity. In chronic renal failure, leptin appears to be increased. However, little is known about leptin regulation during chronic renal failure (CRF).. We measured serum leptin in eight well nourished, chronic hemodialysis patients (seven males, one female) receiving anabolic factors for three days as either recombinant insulin-like growth factor-1 (rhIGF-1) or a combination of recombinant growth hormone (rhGH) plus recombinant IGF-1, in a random cross-over trial.. Serum leptin values were in the range of normal volunteers matched for body mass index. As reported in other conditions, serum leptin was strongly correlated with patients dry body wt (P = 0.01) and body fat (P = 0.0001). Both treatments affected serum leptin in a rapid and opposite manner. RhIGF-1 decreased serum leptin from 11.2+/-20.8 (SD) to 4.3+/-3.8 microg/liter (P = 0.011), whereas the combination of rhGH + rhIGF-1 increased serum leptin from 7.4+/-9.4 to 21.0+/-32.9 microg/liter (P = 0.011). Regression analyses indicated a linear regression between serum leptin and insulin variations after treatment.. This study shows for the first time that both rhIGF-1 and rhGH acutely regulate serum leptin in dialysis patients. Whether leptin changes are explained by the concomitant insulin variation should be further studied under renal failure conditions.

Topics: Adult; Aged; Cross-Over Studies; Female; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Renal Dialysis

The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices.. 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured.. The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD.. In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

Topics: Adiponectin; Body Weight; Child; Cross-Sectional Studies; Hemodiafiltration; Humans; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Renal Dialysis

This cross-sectional study explores the association of adipokines and interleukin-6 (IL-6) with muscle and protein energy wasting (PEW) in children with chronic kidney disease (CKD).. We measured serum adiponectin, leptin, resistin and IL-6 in 53 patients with CKD stage 3-5. Lean tissue (LTI) and fat tissue index (FTI) were estimated by bioimpedance analysis spectroscopy. PEW was defined as muscle wasting [LTI adjusted to height age (LTI HA) z-score < -1.65 SD) and at least 2 of the following: reduced body mass [body mass index adjusted to height age (BMI HA) z-score < -1.65 SD), poor growth [height z-score < -1.88 SD], questionnaire-based decreased appetite, and serum albumin ≤3.8 g/dL.. PEW, observed in 8 (15.1%) patients, was more prevalent in CKD stage 5 (P = .010). Among the adipokines, adiponectin, and resistin levels were significantly higher in CKD stage 5 (P < .001, P = .005). Adiponectin was correlated to LTI HA z-score (Rs = -0.417, P = .002), leptin to FTI z-score (Rs = 0.620, P < .001), while no correlation was observed between resistin and body composition parameters. Resistin was the only adipokine correlated to IL-6 (Rs = 0.513, P < .001). After adjustment for CKD stage and patient age, PEW was associated with adiponectin and IL-6 rise by 1 μg/mL and 10 pg/mL respectively (odds ratio (OR) 1.240, 95% confidence interval (CI) 1.040, 1.478 and OR 1.405, 95% CI 1.075-1.836) but not with leptin, while resistin association with PEW lost its significance.. In pediatric CKD, adiponectin is associated with muscle wasting, leptin with adiposity and resistin with systemic inflammation. Adiponectin and cytokine IL-6 may serve as PEW biomarkers.

Topics: Adipokines; Adiponectin; Cachexia; Child; Cross-Sectional Studies; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Muscles; Renal Insufficiency, Chronic; Resistin

Hemodialyzed patients with poor erythropoietin response tend to have low volume of visceral adipose tissue and score high on malnutrition-inflammation score. This study investigates in-depth the role of leptin and chosen cytokines in the development of malnutrition-inflammation syndrome (MIS) and erythropoietin resistance.. Eighty-one hemodialyzed patients with erythropoietin-treated anemia were enrolled in the study. Their body composition was measured. Erythropoietin resistance index was calculated. Blood samples for leptin, IL-6, IL-18, TNF-alpha, and IL-1-alpha serum levels were drawn.. Leptin showed negative correlation with erythropoietin resistance index (ERI), whilst IL-6 showed the opposite. IL-6 seemed to be linked more to HD parameters and vintage, while TNF-alpha and leptin were more dependent on body composition. IL-18 and IL-1-alpha did not affect nutritional parameters nor ERI.. Modulation of adipokine- and cytokine-related signaling is a promising target in tempering malnutrition in hemodialyzed, and thus achieving better outcomes in anemia treatment. Large clinical studies that target the inflammatory response in hemodialysis, especially regarding IL-6, TNF-alpha, and leptin, would be of great worth.

Topics: Anemia; Erythropoietin; Humans; Inflammation; Interleukin-1; Interleukin-18; Interleukin-6; Kidney Failure, Chronic; Leptin; Malnutrition; Renal Dialysis; Tumor Necrosis Factor-alpha

We explored the associations between serum leptin concentration and cardiovascular prognosis in maintenance hemodialysis patients.. In our prospective study with no intervention, demographics data at baseline were collected from electronic medical records. Serum leptin concentration was determined by ELISA. Patients underwent body composition assessment and echocardiographic measurements after hemodialysis. The primary endpoints were defined as cardiovascular events (CVEs), cardiovascular death (CVD) and all-cause death.. A total of 165 eligible patients aged 51(43-65) y were enrolled and the mean serum leptin concentration was 35.49 (29.98) ng/ml. During a median follow-up of 18 (12-22) months, CVEs occurred in 37 (22.42%) patients and the cardiovascular and all-cause mortality was 10.91% and 21.82%. Serum leptin concentration was associated with CVEs (HR = 0.982, p = 0.003), CVD (HR = 0.934, p = 0.002) and all-cause death (HR = 0.943, p < 0.001). Decreased serum leptin concentration was an independent risk factor for the development of left ventricular hypertrophy (LVH, OR = 0.98, p = 0.007) and peripheral vascular disease (PVD, OR = 0.974, p = 0.007).. Serum leptin concentration can independently predict cardiovascular outcomes and all-cause death in MHD patients. The effects that serum leptin concentration on development of LVH and PVD maybe the potential mechanism.

Topics: Cardiovascular Diseases; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Leptin; Prospective Studies; Renal Dialysis

Kidney disease is a serious public health problem worldwide. It is the fifth top-ranking cause of death in Egypt, causing approximately 3.98% of all deaths. This study's objective was to examine whether an association exists between leptin (- 2548G/A) and uncoupling protein-2 45 bp I/D genes, individually and collectively, in CKD and progression to ESRD.. One hundred patients (69 males, 31 females) aged (47.1 ± 16.11 years) with ESRD, 40 patients (19 males, 21 females) aged (43.15 ± 10.00 years with CKD, and 50 healthy controls (23 males, 27 females) aged (37.84 ± 1.95 years) were enrolled. Polymerase chain reaction (PCR) was employed to measure variation in gene expression among the study groups. The frequency of single nucleotide polymorphisms (SNP) genotypes were identified in controls, CKD and ESRD patients.. Leptin genotypes were associated with lower CKD incidence in control versus study subjects (95% CI = (0.08-0.63), P = 0.01) with risk value equal to 0.22 < 1, G/A genotype was significantly lower in CKD than ESRD groups. There was no correlation between UCP-2 I/D genotype and CKD (P = 0.27). There was no correlation between the UCP-2 gene and the progression to ESRD.. This study suggests that, Leptin - 2548G/A gene may be a promising marker for early detection of ESRD in Egyptian patients. G/A genotype might inhibit the development of CKD to ESRD.

Topics: Adult; Disease Progression; Egypt; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Protective Factors; Uncoupling Protein 2

Maintenance hemodialysis (HD) patients often experience fluctuations of volume status. Although hypervolemia possibly induces systemic inflammation, the relationship between volume status and leptin has not yet been well defined. The aims of this study were to determine the levels of leptin, C-reactive protein (CRP), and ferritin in relation to volume status and to assess the relationship between leptin and volume and inflammatory status in chronic HD patients. This prospective study included 93 HD patients divided, based on evaluation using the body composition monitor, into normovolemic and hypervolemic groups (overhydration/extracellular water [OH/ECW] ≤ 15% and OH/ECW > 15%, respectively). The levels of leptin and inflammatory markers (CRP, ferritin) were determined during a mid-week dialysis session in all patients. There were more hypervolemic patients after 12 months of follow up than at baseline (41% vs. 38%). Hypervolemic patients had significantly lower leptin levels (11.42 ± 19.24 ng/mL vs. 34.53 ± 40.32 ng/mL at baseline and 13.41 ± 22.04 ng/mL vs. 41.54 ± 21.78 ng/mL at 12 months), longer time on dialysis, and poorer nutritional status than normovolemic patients. Inflammation was present regardless of the volume status, but hypervolemic patients had significantly higher CRP and ferritin than normovolemic patients. A statistically significant reverse correlation was found between leptin level, hyperhydration index, and OH/ECW. No significant correlation was found between leptin and inflammatory markers CRP and ferritin.

Topics: Aged; Biomarkers; Blood Volume; C-Reactive Protein; Correlation of Data; Female; Ferritins; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Organism Hydration Status; Prospective Studies; Renal Dialysis

Malnutrition is very complex in patients with end-stage renal disease (ESRD) and is associated with poor prognosis. This is because hemodynamic changes, hormonal changes, persistent inflammatory reactions, and fluid overloads are more complicated as uremia is worsening. Bio-impedance spectroscopy (BIS) is a useful method to estimate fluid balance (Overhydration/ extracellular water, OH/ECW) and nutritional status (Phase angle, PhA). We aimed to evaluate the volume and nutritional status by BIS and to investigate the relationship between the appetite regulating hormones and the parameters of BIS in patients with stage 5 chronic kidney disease not undergoing dialysis (CKD5-ND).. We enrolled a total of 91 CKD5-ND patients. We measured routine serum markers including albumin and NT-proBNP and the appetite regulating hormones, leptin and ghrelin. We defined poor nutritional status as a PhA < 4.5°, and proper nutritional status as a PhA ≥ 4.5°. We also evaluated each patient's nutritional status by assessing their geriatric nutritional risk index (GNRI) and their volume status by measuring NT-proBNP.. Forty-one patients (45%) had poor nutritional status. Patients with a poor nutritional status had significantly higher OH/ECW (29.6 ± 12.7% vs. 6.2 ± 10.3%, p<0.001) and lower levels of leptin (3.8 ± 3.1 vs. 7.0 ± 6.2 ng/mL, p = 0.004) than those with proper nutritional status. PhA was associated with GNRI (r = 0.597, P<0.001) and NT-proBNP was associated with OH/ECW (r = 0.384, P<0.001). Leptin was negatively correlated with OH/ECW (r = -0.288, p = 0.006). In contrast, leptin was positively correlated with PhA (r = 0.263, p = 0.012). In multivariate logistic regression, high level of leptin (OR 7.00, 95% CI 1.74-28.10) was associated with proper nutrition, while an increased OH/ECW (OR 0.65, 95% CI 0.51-0.84) was associated with poor nutrition.. Our study demonstrates that CKD5-ND patients with poor nutrition generally also suffer from excessive body fluid. Low leptin level suggests poor nutrition in CKD5-ND patients. PhA could be used as a nutritional index for ESRD patients.

Topics: Adult; Aged; Biomarkers; Echocardiography; Female; Hormones; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prognosis; Renal Dialysis; Retrospective Studies; ROC Curve; Severity of Illness Index

Cardiovascular (CVS) morbidity and mortality in the peritoneal dialysis patients (PD) is 10-30-fold higher than in the general population. A relatively low level of adiponectin and a higher level of leptin are important predictors of vascular complications as well as CVS events in PD patients. The asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is an important risk factor of CVS morbidity and mortality. It is very important to establish all CVS risk factors in the PD patients to prevent CVS morbidity and mortality in this population. The aim of the study was to determine the plasma concentration of ADMA and adipokines in relation to the protein-energy wasting (PEW) in PD patients. The study was performed in 30 PD patients and in the control group which consisted of 23 healthy volunteers. Plasma levels of hsC-reactive protein, TNF, IL-6, leptin, adiponectin, oxyLDL and ADMA were measured by ELISA method in both groups. The nutritional status was determined by measuring the albumin, body mass index (BMI), the percentage of body fat (%F), lean body mass (LBM) and Subjective Global Assessment Score (SGA). The adequacy of dialysis was estimated by weekly Kt/V. In all PD patients, significantly higher levels of ADMA, leptin, oxyLDL, hsCRP and TNF in comparison to controls were observed. In contrast to well-nourished subjects, patients with PEW, in addition to increased hsCRP, showed significantly higher ADMA. PEW was associated with high levels of ADMA and hsCRP and this could probably be responsible for increased CVS risk in PD patients.

Topics: Adiponectin; Adult; Aged; Arginine; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Energy Metabolism; Humans; Interleukin-6; Kidney Failure, Chronic; Leptin; Lipoproteins, LDL; Middle Aged; Peritoneal Dialysis; Risk Factors; Tumor Necrosis Factor-alpha

Leptin is a hormone made by adipocytes and associated with hypertension, inflammation, and coronary artery disease. Low serum leptin level was associated with higher risk of death in patients with advanced chronic kidney disease. Little is known about the association of serum leptin with outcomes in kidney transplant recipients.. Prospective prevalent cohort.. We collected sociodemographic and clinical parameters, medical and transplant history, and laboratory data of 979 prevalent kidney transplant recipients. Associations between serum leptin level and death with a functioning graft, all-cause death, and death-censored graft loss over a 6-year follow-up period were examined in survival models.. Serum leptin levels showed moderate negative correlation with eGFR (R = -0.21, P < .001) and positive correlations with BMI (R = 0.48, P < .001) and C-reactive protein (R = 0.20, P < .001). Each 10 ng/mL higher serum leptin level was associated with 7% lower risk of death with functioning graft (hazard ratio [HR] (95% confidence interval [CI]), 0.93 (0.87-0.99)), and this association persisted after adjustment for confounders: HR (95% CI), 0.90 (0.82-0.99). Similar associations were found with all-cause death as outcome. The association between serum leptin level and risk of graft loss was nonlinear, and only low serum leptin level was associated with higher risk of graft loss.. In prevalent kidney transplant recipients, lower serum leptin was an independent predictor of death.

Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Female; Follow-Up Studies; Graft Rejection; Humans; Inflammation; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Socioeconomic Factors; Treatment Outcome

The adipocytokine leptin is an independent cardiovascular risk factor and exerts proatherogenic effect. Pre-existing vascular disease is an important cause of arteriovenous fistula (AVF) maturation failure. We explored the association between serum leptin, pre-existing vascular disease, and AVF maturation failure in incident hemodialysis patients.. Vein samples from 62 patients were collected at the time of AVF creation. Pre-existing vascular disease was evaluated with histologic changes and immunohistochemical characteristics of cellular phenotypes in intima. AVF maturation failure was defined as an AVF that could not be used successfully by the third month after its creation.. The prevalence of body mass index ≥30 kg/m. Obesity-related higher fistula maturation failure rate may be partly mediated by higher leptin level-associated pre-existing vascular diseases in end-stage renal disease patients. Decreased expression of leptin receptor may be related to this association.

Topics: Adult; Aged; Aged, 80 and over; Arteriovenous Shunt, Surgical; Biomarkers; Body Mass Index; Female; Humans; Hyperplasia; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Receptors, Leptin; Renal Dialysis; Republic of Korea; Risk Factors; Treatment Failure; Up-Regulation; Vascular Diseases; Veins

Cytokines are essential mediators of immune response. Chronic renal failure patients suffer from chronic inflammation that results from factors such as impaired renal function, accumulation of uremic toxins and bio incompatibility of dialyzer membranes. These patients are also at increased risk of cardiovascular diseases. We have evaluated cytokines, adipocytokines and inflammatory markers in patients with chronic renal failure undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD).. We have determined serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), leptin and ghrelin levels of chronic renal failure patients treated with either HD (n = 20) or CAPD (n = 20). TNF-α, IL-6, ghrelin and leptin measurements were performed by commercially available kits based on enzyme-linked immunosorbent assay (ELISA) method. hsCRP levels were determined by turbidimetric methods.. Serum TNF-α and IL-6 levels of patients on HD were significantly higher than those of the ones on CAPD (p < 0.05). Ghrelin, leptin and hsCRP concentrations were similar in both groups.. We can conclude that cytokine production is more obvious in HD process.

Topics: Adipokines; Adult; Aged; Biomarkers; C-Reactive Protein; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Tumor Necrosis Factor-alpha

In chronic kidney disease (CKD) patients, decreased heart rate variability (HRV) reflects impaired cardiac automatic nervous function and high risk of cardiovascular disease (CVD). Lower HRV in patients with severe secondary hyperparathyroidism (SHPT), a clinical manifestation of CKD-mineral and bone disorder (CKD-MBD), could be reversed by parathyroidectomy (PTX). It has been proved that leptin interacts with the autonomic nervous function. However, the associations between leptin and HRV in CKD patients and their longitudinal changes in SHPT patients after PTX are still unknown.. This was a cross-sectional study including 141 stage 5 CKD patients, and a prospective study in 36 severe SHPT patients with PTX. HRV was measured by Holter and serum leptin was measured by ELISA. Serum leptin levels were adjusted for body mass index (BMI) and transformed using natural logarithm (lnleptin/BMI).. With a gradient of lnleptin/BMI across quartiles from Q1 to Q4 in CKD patients, HRV indices showed no differences among quartiles. Patients in Q1 group had higher mean 24 h heart rates, and lower ln(very low frequency) (lnVLF) than other quartiles, although there were no statistically significant difference. In multivariate stepwise regression, serum leptin/BMI was an independent predictor for low frequency/high frequency. HRV indices and lnleptin/BMI levels were increased in severe SHPT patients after PTX. Compared to other quartiles, SHPT patients in Q1 group had larger improvement of lnVLF after PTX.. Circulating leptin levels may be a novel treatment target to reduce CVD risk in advanced CKD-MBD patients.

Topics: Adult; Body Mass Index; Chronic Kidney Disease-Mineral and Bone Disorder; Cross-Sectional Studies; Female; Follow-Up Studies; Heart Rate; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Parathyroidectomy; Prospective Studies

The aim of the study was to examine the prevalence of protein-energy wasting (PEW) in hemodialysis (HD) and peritoneal dialysis (PD) patients in our center and determine whether adiponectin and leptin are involved in the development of PEW.. Prospective (18 months).. University Hospital of Heraklion, Crete, Greece.. Seventy-four end-stage-renal-disease patients, 47 on HD and 27 on PD.. At three sequential time points (baseline, 6 and 18 months) anthropometric, nutritional and inflammatory status data were collected. Serum adiponectin and leptin were also assessed at each time point. Patients were allocated to 3 strata according to PEW severity (0, 1-2 and ≥3 criteria for PEW).. Adiponectin and leptin levels were greater among PD compared to HD patients (p≤0.035). Adiponectin levels were incrementally greater across increasing strata of PEW (p≤0.002). Leptin showed the opposite trend, with lower levels in malnourished patients and higher levels in patients with zero PEW criteria (p≤0.042). Alterations of adiponectin levels during the observation period were dependent on PEW stratum (p≤0.021) and mode of dialysis (p≤0.002), after adjustment for age, dialysis vintage, gender and fat mass index. Particularly, adiponectin levels increased over time in HD patients with ≥3 criteria for PEW, whereas adiponectin levels decreased in PD patients with ≥3 criteria for PEW throughout the study. Leptin alterations over time were not affected by dialysis mode or PEW stratification.. Our study provides evidence that increased adiponectin and decreased leptin levels are independently associated with PEW and thus, poor prognosis.

Topics: Adiponectin; Adolescent; Adult; Aged; Aged, 80 and over; Anthropometry; Body Composition; Comorbidity; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Prospective Studies; Protein-Energy Malnutrition; Renal Dialysis; Young Adult

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with chronic kidney disease (CKD) including kidney transplant recipients (KTR). Secondary lipid metabolism disorders, endothelial dysfunction, and inflammation enhance the risk of CVD development in these patients. The aim of the present study was to investigate the lipid profile, adiponectin, leptin, nitric oxide (NO), and high sensitivity C-reactive protein (hs-CRP) levels in KTR and to compare these parameters with those of the patients with chronic renal failure (CRF), hemodialysis (HD) patients, and healthy controls.. Serum adiponectin and leptin levels were measured by radioimmunoassay; hs-CRP was determined immunoturbidimetrically. Determination of NO was based on the Griess reaction.. Compared with the control group, serum NO and adiponectin levels were significantly higher in the KTR, CRF, and HD groups; hs-CRP levels were significantly higher in the KTR and HD groups; leptin levels were significantly higher in the KTR. In addition, serum NO level was significantly higher in the KTR compared to CRF cases. Adiponectin correlated positively with high density lipoprotein-cholesterol in the control and patient groups. A positive correlation was observed between hs-CRP and NO in the KTR and the patients with CRF. Serum adiponectin levels were inversely correlated with hs-CRP and leptin in the HD group.. KTR suffer from inflammation and accompanying changes in levels of adipocytokines and NO which contribute to the increased risk of CVD in these patients.

Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Inflammation; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Middle Aged; Nitric Oxide; Renal Dialysis; Transplant Recipients; Turkey

Hyperleptinemia and metabolic acidosis (MA) are frequently observed in patients on hemodialysis (HD). While the role of leptin in patients on HD is not completely understood, HD only partially corrects MA. Both leptin and acidosis have effect on bone disease. The goal of the present study was to evaluate the effects of MA correction on chronic kidney disease-mineral and bone disorder laboratory parameters and leptin levels.. Forty-eight patients on HD, aged 43±19 years, were prospectively studied. Individual adjustments in the bicarbonate dialysate concentration were made to maintain pre-dialysis concentration≥22 mEq/l. Blood gas analysis was done monthly for 4 months (M1-M4).. From M0 to M4, serum albumin increased (from 3.5 ±0.3 to 4.0±0.3 g/l, p<0.0001) while β2 microglobulin decreased (from 27.6±8.3 to 25.8±6.8 µg/ml, p=0.025). Serum leptin decreased in all but three patients, as well as leptin/adiponectin ratio (p<0.0001). There was a decrease in ionized serum calcium (from 5.0±0.5 to 4.7±0.5 mg/dl, p =0.002) and an increase in parathyroid hormone (PTH) [from 191 (85, 459) to 446 pg/ml (212, 983), p<0.0001] and in serum phosphate (from 5.4±1.4 to 5.8±1.1 mg/dl, p=0.048).. MA correction in HD patients can decrease leptin, an atherogenic marker. The impact of such treatment extends to uremic bone disease, as decrease in serum calcium and increase in PTH. However, this could be an undesirable effect because it may aggravate a secondary hyperparathyroidism. Whether the reduction in leptin levels has impact on outcomes in patients on hemodialysis deserves further investigation.

Topics: Acidosis; Adiponectin; Adult; beta 2-Microglobulin; Bicarbonates; Blood Gas Analysis; Calcium; Dialysis Solutions; Female; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Parathyroid Hormone; Phosphates; Prospective Studies; Renal Dialysis; Serum Albumin; Sex Factors; Young Adult

Based on evidence that leptin and adiponectin are removed from circulation primarily by the kidney, we designed a study to examine the longitudinal changes of these adipokines during the first week after kidney transplantation (KTx) and to test the hypothesis that higher levels of leptin and/or adiponectin could be early biomarkers of delayed graft function (DGF=dialysis requirement during the first post-transplant week) and acute rejection.. Repeated-measures prospective study.. Forty consecutive adult patients with end-stage renal disease who were undergoing KTx. Leptin and adiponectin were measured in blood samples that were collected before (day-0) and after KTx (days-1, 2, 4 and 7). Linear mixed-models, receiver operating characteristic and area under curve (AUC-ROC) were used.. At post-transplant day-1, leptinemia and adiponectinemia declined 43% and 47%, respectively. At all times studied after KTx, the median leptin levels were significantly higher in patients developing DGF (n=18), but not adiponectin levels. Shortly after KTx (day-1), leptin values were significantly higher in DGF recipients in contrast to patients with promptly functioning kidneys, approximately two times higher when controlling for gender and BMI. The leptin reduction rate between pre-tranplant and one-day after KTx moderately predicted DGF (AUC=0.73). On day-1, serum leptin predicted DGF (AUC-ROC=0.76) with a performance slightly better than serum creatinine (AUC-ROC=0.72), even after correcting for BMI (AUC-ROC=0.73). Separating this analysis by gender showed that the performance of leptin in predicting DGF for male gender (AUC-ROC=0.86) improved.. Kidney graft function is an independent determinant of leptin levels, but not of adiponectin. Leptin levels at day-1 slightly outperformed serum creatinine in predicting the occurrence of DGF, and more accurately in male gender. No significant association was detected with acute rejection.

Topics: Adiponectin; Adult; Biomarkers; Cohort Studies; Delayed Graft Function; Early Diagnosis; Female; Hospitals, Urban; Humans; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Portugal; Postoperative Period; Prospective Studies; Sensitivity and Specificity; Up-Regulation

Leptin is a hormone and a proinflammatory cytokine secreted from adipocytes, which functions to suppress appetite in healthy persons. Serum leptin levels are significantly elevated in patients with end-stage renal disease (ESRD) primarily due to decreased clearance by the kidneys The consequence of hyperleptinemia in ESRD is not fully understood. We aimed to investigate the association between serum leptin levels and nutrition/inflammation status in non-obese chronic hemodialysis (HD) patients.. 65 chronic, anuric, nonobese (body mass index (BMI) < 25 kg/m2) HD patients were included in this cross-sectional study. Demographic, anthropometric, and biochemical data were obtained from all patients to determine nutrition and inflammation status. Patients were classified into the 3 groups according to serum leptin levels; group 1 (low leptin, n = 9), group 2 (normal leptin, n = 31), and group 3 (high leptin, n = 25).. Mean age and duration on dialysis of 65 patients (male/female: 34/31) were 51.6 ± 17.8 years and 78.0 ± 67.9 months, respectively. Serum leptin levels increased with older age, female gender, higher BMI and triceps skinfold thickness. Elevated serum leptin levels were significantly associated with good nutritional status parameters, such as higher albumin (p = 0.001), prealbumin (p = 0.033), total iron binding capacity (p = 0.045), total cholesterol (p = 0.041), and lower malnutrition inflammation score (MIS) (p = 0.002). Serum leptin levels remained a negative correlation with MIS after adjustments made for BMI. No correlation was established between leptin and inflammation parameters including ferritin, highly sensitive C-reactive protein (hs-CRP), and tumor necorsis factor alpha (TNF-α).. Elevated serum leptin levels seem to be associated with good nutritional status. However, there was no correlation between leptin and inflammatory status.

Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Renal Dialysis

Excessive relative interdialytic weight gain (RIDWG, %) is an important risk factor for long-term adverse cardiovascular outcomes in chronic hemodialysis (HD) patients. On the other hand, it may also be an index of good appetite and nutritional status. We aimed to assess the relationship between RIDWG and appetite, nutrition, inflammation parameters of chronic HD patients.. 100 chronic anuric HD patients were enrolled in this prospective study between January 2013 and January 2014. Patients with hospitalization, major surgery, obvious infectious/inflammatory disease, end-stage liver disease, malignancies, and malabsorption syndromes were excluded. Patients were divided into 3 groups according to their RIDWG levels; group 1 = RIDWG < 3%, group 2 = RIDWG: 3 - 5%, and group 3 = RIDWG > 5%.. Group 3 patients were younger (p = 0.011) and had a lower body mass index (BMI) (p = 0.014). Nutrition and inflammation parameters including malnutrition inflammation score (MIS), serum albumin, prealbumin, triceps skinfold thickness, hs-CRP, and TNF-α ere not significantly different between the groups. Leptin and leptin/BMI ratio were significantly lower in group 3 (p = 0.001). RIDWG was negatively correlated with age (p = 0.001, r = -0.371), BMI (p = 0.001, r = -0.372), leptin (p = 0.001, r = -0.369), leptin/BMI (p = 0.001, r = -0.369). After adjustment for BMI in linear regression analyis, leptin/BMI remained significantly correlated with RIDWG (p = 0.024).. This study revealed that RIDWG was associated with younger age, lower BMI and dry weight, and lower serum leptin levels. More detailed studies are needed to validate and dissect the mechanisms of these findings.

Topics: Adult; Aged; Body Mass Index; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Prospective Studies; Renal Dialysis; Serum Albumin; Weight Gain

Chronic renal failure (CRF) compromises nutrition, growth, puberty, glycometabolic homeostasis, and adipokine secretion (i.e. adiponectin, resistin, and leptin). Adipokines play a role in the clinical outcome, but data in paediatric patients is scant.. To evaluate the link between kidney function, adiponectin, resistin, leptin, hormonal status, nutritional state and late outcome of CRF children.. We studied leptin, adiponectin and resistin levels in 31 CRF patients (19 males, 12 females, aged 12.1 ± 4.47 years) managed conservatively, and 30 healthy age- and gender-matched controls. Clinical, auxological, biochemical, hormonal data, glucose and insulin levels were correlated with adipokine levels.. Six percent of patients had glycaemia T0' > 126 mg/dl, 23 % glycaemia T60' > 126, and 23 % glycaemia T120' ≥ 140. Glycated haemoglobin (HbA1c) measured during follow-up was in the normal range in all patients (4-5.6 %). Insulinaemia was significantly higher in CRF patients than controls. Homeostatic model of assessment-insulin resistance (HOMA-IR) levels were more elevated in patients (32 % had HOMA-IR > 2.5) than controls. Leptin levels were significantly higher in CRF patients than controls and differed significantly between males and females. Leptin correlated significantly with creatinine, body mass index (BMI), BA, pubertal stage, insulin-like growth factor 1, and HOMA-IR in females. Adiponectin levels were significantly higher in patients than controls, higher in patients with BMI < 85th centile and significantly inversely correlated to BMI, BA, haemoglobin, ferritin, proteins, albumin, and creatininuria. Resistin levels showed a direct correlation with C-reactive protein and an inverse correlation with haemoglobin.. Normal resistin levels are an expression of both adequate nutritional state and controlled inflammatory state. Adiponectin could protect against chronic inflammation, atherosclerosis, and cardiovascular diseases. Preventing obesity and ensuring a correct nutritional state are primary goals for physicians following children with CRF. Adipokines could be a useful marker in the follow-up.

Topics: Adiponectin; Adolescent; Adolescent Nutritional Physiological Phenomena; Age Factors; Biomarkers; Blood Glucose; Cardiovascular Diseases; Case-Control Studies; Child; Disease Progression; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Nutritional Status; Obesity; Prognosis; Resistin; Risk Factors; Time Factors

Our aim is to study the correlations of leptin and adiponectin with inflammation markers, body composition and lipid profile in end stage renal disease (ESRD) patients.. Phase angle values and fat mass as calculated using BIA, Malnutrition-Inflammation Score (MIS), leptin, adiponectin, IL-6, IL-8 triglycerides, cholesterol and other common serum markers' concentrations were analyzed using simple and multiple linear regression models in 47 hemodialysis patients.. In contrast to leptin, adiponectin is inversely correlated to BMI and fat mass in hemodialysis patients. Triglycerides were the only parameter that retained its statistical correlation significance with adiponectin in the multiple regression model.. Fat mass is of important consideration when calculating adipokines levels and their possible correlations with other variables. The inverse correlation of adiponectin with triglycerides levels should be further delineated due to the important role of vascular diseases in total mortality and morbidity of ESRD patients.

Topics: Adiponectin; Adiposity; Body Composition; Body Height; Body Weight; C-Reactive Protein; Cholesterol; Female; Humans; Interleukin-6; Interleukin-8; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Renal Dialysis; Triglycerides

Topics: Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Renal Dialysis

Prior studies evaluating the relationship between leptin and outcomes in chronic kidney disease patients have shown conflicting results. Our aim was to evaluate the association of serum leptin with all-cause and cardiovascular disease (CVD)-related mortality in stable maintenance hemodialysis patients.. We carried out an observational prospective cohort study of 53 patients on maintenance hemodialysis. The follow-up period was 5 years. Leptin levels were measured at baseline before the start of a hemodialysis session. Proportional hazards models were used to evaluate the relationship between leptin and all-cause and CVD-related mortality.. During the follow-up period, 26 patients (49.1%) died. Fifteen of 26 deaths (57.7%) were attributable to CVD. Cox proportional hazards analysis showed that a leptin level equal to or greate than the median value (3.45 ng/mL) was associated with lower mortality rates (hazard ratio, 0.211; 95% confidence interval, 0.062 to 0.723; P = .01) after multivariable adjustment for potential confounders. However, leptin was not an independent risk factor for CVD-related mortality.. There was a converse association between the serum leptin concentration and mortality in stable maintenance hemodialysis patients. Low serum leptin concentration is an independent risk factor of all-cause mortality in stable maintenance hemodialysis patients, but may not be linked with CVD-related mortality.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Cause of Death; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Survival Rate

Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Failure, Chronic; Leptin; Lovastatin; Male

Topics: Cardiovascular Diseases; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Renal Dialysis

In this study, it is aimed to compare the serum leptin and PAI-1 levels and evaluate their relationship in children on hemodialysis (HD) and peritoneal dialysis (PD).. Thirty-six patients on HD (mean age: 15.0 ± 2.8 years), 19 patients on PD (mean age: 13.0 ± 3.5 years) and 15 healthy subjects (mean age: 14.5 ± 2.7 years) were included in the study. Laboratory investigations included blood count, biochemical parameters, serum iron, iron binding capacity, parathormone, erythrocyte sedimentation rate, C-reactive protein (CRP), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, serum leptin and PAI-1 levels.. Serum leptin levels were significantly higher in HD group than in control group when the effects of BMI and sex were controlled, while PD and control groups had similar leptin levels. PAI-1 levels were also significantly higher in HD group than in control group, while there was no statistically significant difference in PAI-1 levels of PD and control group. PAI-1 levels and leptin levels were significantly correlated, which was independent of the effect of BMI in both HD and PD groups when they are evaluated separately.. Results of our study showed that HD patients had higher leptin and PAI-1 levels and leptin and PAI-1 levels were correlated significantly in both patient groups. The effect of elevated serum leptin and PAI-1 levels on the cardiovascular complications remains to be established.

Topics: Adolescent; Age Factors; Body Mass Index; Cardiovascular Diseases; Case-Control Studies; Child; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Peritoneal Dialysis; Plasminogen Activator Inhibitor 1; Risk Factors; Sex Factors

Resistin is a major adipose tissue cytokine implicated in insulin resistance, inflammation and vascular damage. This cytokine is raised in patients with end-stage kidney disease (ESKD) but the relationship between resistin and major clinical outcomes has not been investigated in this population.. We studied the mutual relationship between resistin and the two major adipokines (adiponectin and leptin) and the interaction between resistin and adiponectin (ADPN) and all-cause and cardiovascular (CV) mortality in a cohort of 231 haemodialysis patients followed up for 57 ± 44 months.. Plasma resistin was substantially raised in ESKD patients when compared with healthy subjects (P < 0.001). On univariate analysis, resistin was related inversely to ADPN (r = -0.14, P = 0.04) and directly to C-reactive protein (r = 0.15, P = 0.03), but was largely independent of leptin (r = 0.08, P = 0.24) and the HOMA-IR index (r = -0.04, P = 0.51). During the follow-up, 165 patients died (96 for CV causes). On both univariate (all-cause mortality: P = 0.004; CV mortality P < 0.001) and multivariate (all-cause mortality: P = 0.01; CV mortality P < 0.001) Cox regression analyses, the effect of resistin on study outcomes was closely dependent on ADPN levels. There was a consistent excess risk for all-cause (P = 0.002) and CV mortality (P = 0.003) by plasma resistin (20 ng/mL) in patients in the first ADPN tertile, but no risk excess for these outcomes was apparent in patients in the third tertile.. This study indicates that resistin predicts death and fatal CV events depending on plasma ADPN levels. These findings underscore the importance of the interaction among adipokines for the prediction of adverse clinical outcomes in ESKD.

Topics: Adiponectin; Adipose Tissue; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Regression Analysis; Renal Dialysis; Resistin; Survival Rate

Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number of beneficial cardiotropic effects in experimental studies. We hypothesized that obestatin alteration in hemodialysis patients may link to clinical outcomes. This cross-sectional study with prospective followup for almost 4 years was performed on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6, and various nutritional markers were measured. Patients with low obestatin levels, defined as a level less than median, had a worse all-cause mortality and cardiovascular mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients continued to be significant after adjustment for various confounders for all-cause mortality. Across the four obestatin-TNF-α categories, the group with low obestatin and high TNF-α (above median level) exhibited a worse outcome in both all-cause mortality and cardiovascular mortality. Clinical characteristics of patients in low obestatin high TNF-α group did not differ from other obestatin-TNF-α categorized groups. In summary, low serum obestatin concentration is an independent predictor of mortality in prevalent hemodialysis patients. Novel interactions were observed between obestatin and TNF-α, which were associated with mortality risk, especially those due to cardiovascular causes.

Topics: Biomarkers; Cardiovascular Abnormalities; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Tumor Necrosis Factor-alpha

Associations between 25 hydroxy vitamin D [25(OH)D], adipokines levels, and insulin resistance have been reported. The aim of this study was to explore the effects of cholecalciferol supplementation on vitamin D levels, insulin resistance, leptin, and adiponectin levels in vitamin D-deficient peritoneal dialysis (PD) patients.. In nineteen vitamin D-deficient PD patients, who were treated with cholecalciferol, fasting serum glucose, insulin, adiponectin, leptin, 25(OH)D and parathyroid hormone (PTH) were measured before and after cholecalciferol replacement therapy. Eighteen (94.7 %) PD patients with vitamin D deficiency were receiving active vitamin D compounds (alphacalciferol) for PTH control. Alphacalciferol dosing was kept constant during treatment with cholecalciferol.. While mean 25(OH)D significantly increased from (10.2 ± 4.9 ng/ml) to (82.9 ± 56.5 ng/ml) (p < 0.05), mean homeostatic model assessment-insulin resistance index significantly decreased from (4.6 ± 3.6) to (2.8 ± 2.0) after cholecalciferol replacement therapy (p < 0.05). Serum leptin levels (12.9 ± 17.6 ng/ml) significantly increased (18.1 ± 19.5 ng/ml) (p < 0.05), while there was no change in serum adiponectin, calcium, and phosphate after vitamin D replacement. Serum PTH levels significantly decreased from 551.9 ± 276.6 pg/ml to 434.0 ± 273.4 ng/ml.. Cholecalciferol replacement therapy significantly decreases PTH levels and insulin resistance. The results of this study need to be confirmed in larger clinical trials.

Topics: Adipokines; Cholecalciferol; Female; Follow-Up Studies; Humans; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Pilot Projects; Prospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins

Leptin is the protein product of the obesity gene, which is produced in fat tissue. It was originally thought to be involved only in the regulation of food intake and energy balance. We aimed to investigate the relationship of serum leptin levels with bone mineral density (BMD) and biochemical markers of bone turnover in patients on hemodialysis (HD). This study included 72 patients (43 males and 29 females), whose mean age was 55.1 ± 11.4 years, mean body mass index was 23.13 ± 2.75 kg/m 2 and mean duration on HD was 5 ± 3.4 years. The BMD values were calculated using dual-energy X-ray absorptiometry (DEXA) at the femoral neck and lumbar spine. Blood samples were taken for leptin, intact parathyroid hormone (I-PTH), bone alkaline phosphatase (BAP), calcium (Ca), phosphate (P) and albumin. The leptin levels were higher in females than in males (22.3 ± 19.6 vs 20.8 ± 23), but this difference was not significant. The serum leptin level had a strong positive correlation with Ca levels in the female patients (r = 0.659 and P = 0.01) and a negative correlation with albumin levels (r = -0.461 and P = 0.01). No correlation was found with age, BMI, duration on dialysis, BMD and serum levels of PTH, BAP and P for the entire patient group or either gender separately. The serum leptin level was significantly lower in females with PTH >300 pg/mL when compared with patients with PTH = 100-300 pg/mL (86 ± 85 vs 47 ± 48) (P = 0.011).Women with BAP <300 IU/L had significantly higher serum leptin than those with BAP 300-600 IU/L (P = 0.024). Women with Ca <8.5 mg/dL had significantly lower serum leptin levels compared with those with Ca levels of 8.5-10.5 mg/dL (P = 0.011). There was no significant difference between the two genders among variables such as age, BMI, duration on dialysis, serum leptin, I-PTH, Ca, P, BAP, albumin and BMD of the femoral neck and lumbar spine.

Topics: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Biomarkers; Body Mass Index; Bone Density; Bone Diseases, Metabolic; Cross-Sectional Studies; Female; Femur Neck; Follow-Up Studies; Humans; Incidence; Iran; Kidney Failure, Chronic; Leptin; Lumbar Vertebrae; Male; Middle Aged; Obesity; Parathyroid Hormone; Prognosis; Renal Dialysis; Retrospective Studies

Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia.

Topics: Adipokines; Adiposity; Adult; Appetite; Body Composition; C-Reactive Protein; Calcium-Binding Proteins; Case-Control Studies; DNA-Binding Proteins; Eating; Female; Humans; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nerve Tissue Proteins; Nucleobindins; Nutritional Status; Renal Dialysis; Tumor Necrosis Factor-alpha

The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation.. Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 ± 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 ± 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed.. There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed-transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF-α levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group.. Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts.

Topics: Adult; Appetite; Biomarkers; C-Reactive Protein; Female; Ghrelin; Humans; Inflammation; Insulin-Like Growth Factor I; Interleukin-6; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Renal Dialysis; Transplantation, Homologous; Treatment Failure; Tumor Necrosis Factor-alpha

To evaluate the body composition and inflammatory status in patients on hemodialysis (HD) according to the cutoff of 23 kg/m² for the body mass index (BMI).. Forty-seven patients (30 men, 11 diabetics, 53.8 ± 12.2 y of age, 58.2 ± 50.9 mo on HD) were studied. Anthropometric data and handgrip strength were evaluated. C-reactive protein, tumor necrosis factor-α, leptin, and interleukin-6 were measured. Mortality was assessed after 24 mo of follow-up.. Nineteen patients (40.4%) presented BMI values lower than 23 kg/m² and leptin levels, midarm muscle area, and free-fat mass were significantly lower in these patients. The prevalence of functional muscle loss according to handgrip strength was not different between the BMI groups. The sum of skinfold thicknesses, the percentage of body fat, fat mass, the fat mass/free-fat mass ratio, and waist circumference were significantly lower in patients with a BMI lower than 23 kg/m², but the mean values did not indicate energy wasting. Patients with a BMI higher than 23 kg/m² presented a higher prevalence of inflammation and higher waist circumference and body fat values. The adiposity parameters were correlated with C-reactive protein and leptin. A Cox multivariate regression analysis demonstrated that C-reactive protein, tumor necrosis factor-α, and interleukin-6 predict cardiovascular mortality.. Patients on HD with a BMI lower than 23 kg/m² did not present signs of energy wasting, whereas those with a BMI higher than 23 kg/m² had more inflammation, probably because of a greater adiposity. Thus, the BMI value of 23 kg/m² does not seem to be a reliable marker of protein-energy wasting in patients on HD.

Topics: Adult; Aged; Biomarkers; Body Composition; Body Fluid Compartments; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Diabetes Complications; Female; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Muscle, Skeletal; Obesity; Proportional Hazards Models; Protein-Energy Malnutrition; Reference Values; Renal Dialysis; Reproducibility of Results; Wasting Syndrome

In patients with end-stage renal disease (ESRD), circulating adipokine levels are increased due to decreased renal clearance, irrespective of obesity. However, whether adipokines play a role in the development of insulin resistance (IR) in non-obese ESRD patients is unknown. We conducted a cross-sectional study to identify factors associated with IR in 62 non-obese patients on peritoneal dialysis (PD). Non-obesity was defined as body mass index (BMI) <25 kg/m(2). IR was determined using homeostatic model assessment-IR (HOMA-IR). We also measured serum concentrations of adiponectin, leptin, resistin, high-sensitivity C-reactive protein (hsCRP), and IL-6. The average BMI of the study patients was 21.6 kg/m(2). When patients were divided into two groups according to the median value of HOMA-IR, serum adiponectin levels were significantly lower in patients with HOMA-IR > 1.85 than in those with HOMA-IR ≤1.85, whereas serum concentrations of leptin and resistin did not differ between the two groups. In addition, log-transformed HOMA-IR was negatively correlated with adiponectin (γ = -0.464, P < 0.001) and log-transformed high-density lipoprotein cholesterol (γ = -0.250, P = 0.050) and positively correlated with age (γ = 0.334, P = 0.008) and triglyceride (γ = 0.392, P = 0.002). However, resistin, log-transformed leptin and log-transformed hsCRP were not associated with HOMA-IR. In a multiple linear regression model, adiponectin was independently associated with HOMA-IR (β = -0.023, P = 0.015). In conclusion, this study suggests that low circulating adiponectin levels might be involved in IR even in non-obese patients undergoing PD.

Topics: Adiponectin; Adult; Aged; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Cross-Sectional Studies; Female; Homeostasis; Humans; Insulin Resistance; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Models, Biological; Peritoneal Dialysis; Resistin

Overweight and obesity are associated to a higher cardiovascular risk and mortality in the general population and conflicting findings exist in the dialysis population. Adipokines (Leptin, adiponectin) produced in adipocytes may play a role in that process, and inflammatory parameters (CRP, IL-6) may be markers for it. Nevertheless, obtaining dry weight is today one of the main aims of adequacy in dialysis because overhydration is a clear mortality predictor.. The aim of this study was to analyse body composition using an impedance spectroscopy technique in patients on haemodialysis (HD): and evaluate overweight and overhydration prevalence and its possible relation with adipokines, inflammatory and nutritional parameters, HD technique (Conventional [CHD], on-line haemodiafiltration [OL-HFD]) and erythropoietin needs.. In a cross-sectional observational study, a pre-HD multifrequency bioimpedance spectroscopy (BIS) was performed in the middle of the week on 77 HD outpatients: 56 CHD and 21 OL-HFD. Patients were considered overweight when Body Mass Index (BMI) was ≥25kg/m² and overhydrated when overhydration normalised for extracellular water was higher than 0.15l. Clinical and biochemical parameters were analysed and IL-6, leptin and adiponectin levels were determined. This information was analysed in overweight and non-overweight, regular and overhydrated patients and both HD techniques.. 50% of patients fulfilled overweight criteria and 21% were pre-HD overhydrated. Overweight patients had a superior fat and extracellular water content (P<.001). Leptin (P=.001) and CRP (P=.036) levels were higher and adiponectin levels were lower (P=.003). An inverse correlation did exist between BMI and lean mass (P=.01). Nutritional markers (prealbumin, albumin, total proteins, creatinine and transferrin) were related to lean mass (P=.05). Comparing both HD techniques, a lower fat content was observed in OL-HFD (P=.049) without overhydration differences. In the univariate analysis, age, fat, extracellular/intracellular water ratio, leptin, hipoadiponectinaemia, lower lean mass and CHD technique were predictors of overweight. In the multivariate analysis, hipoadiponectinaemia (OR: 0.86; IC: 0.76-0.98), lean mass (OR: 0.89; IC: 0.84-0.94) and OL-HFD technique (OR: 0.200; IC: 0.04-0.99) predicted the absence of overweight.. This observational study emphasises the high prevalence of overweight in the outpatient haemodialysis population, as long as overweight is related with fat and extracellular water. Furthermore, it is accompanied by higher inflammation and leptin levels and lower levels of adiponectin. The use of the OL-HFD technique is associated to less overweight and fat content. Bioimpedance may prove to be a valuable ally for decisions regarding weight changes in dialysis patients.

Topics: Adipokines; Adiponectin; Aged; Biomarkers; Blood Proteins; Body Composition; Body Mass Index; Creatinine; Cross-Sectional Studies; Dielectric Spectroscopy; Female; Hemodiafiltration; Humans; Inflammation Mediators; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Overweight; Renal Dialysis; Transferrin; Water-Electrolyte Imbalance

The association between nutritional status, antioxidant human paraoxonase-1 (PON1) activity and low grade inflammation in hemodialized (HD) patients with chronic kidney disease (CKD) is unclear. The aim of this study was to determine PON1 paraoxonase and lactonase activities, ADMA, adiponectin and leptin concentrations, and to clarify the relationship between paraoxonase activity and a set of cardiovascular risk factors in malnourished, normal weight and obese HD patients; 114 HD patients with end-stage renal failure were enrolled.. Leptin levels were significantly higher and PON1 paraoxonase activities were significantly lower in obese patients compared to the other groups. Plasma adiponectin concentration was significantly lower in obese subjects compared to malnourished patients. Paraoxonase activity was negatively correlated with CRP level in HD and malnourished patients. Furthermore, we found significant inverse correlation between paraoxonase activity and BMI in the whole patient group. In multiple regression analysis, PON1 lactonase activity, CRP level and leptin concentration proved to be independent predictors of paraoxonase activity.. Despite the previous findings of reverse epidemiology for the mortality rate of HD patients, further studies are needed to clarify the effects of nutritional state on atherosclerosis in obese and malnourished patients with end-stage renal failure.

Topics: Adiponectin; Aged; Aryldialkylphosphatase; Atherosclerosis; Biomarkers; C-Reactive Protein; Comorbidity; Humans; Kidney Failure, Chronic; Leptin; Malnutrition; Middle Aged; Nutritional Status; Obesity; Regression Analysis; Renal Dialysis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors

the relationships between the adipose tissue cytokines leptin and adiponectin (ADPN) and clinical outcomes have not been well studied in haemodialysis (HD) patients and remain highly controversial. As central obesity is an important modifier of the effect of various risk factors for clinical outcomes, we tested the hypothesis that waist circumference (WC) modifies the link between these cytokines and both overall and cardiovascular death in HD patients.. a total of 537 HD patients participated in a prospective cohort study.. leptin and ADPN were inversely related to each other and robustly associated with WC (P < 0.001). During follow-up (average 29 months, range 1-47 months) 182 patients died, including 115 from cardiovascular causes. In analyses adjusting for potential confounders, there were strong interactions between leptin and WC in relationship to both all-cause (P < 0.001) and cardiovascular death (P = 0.002). Accordingly, a fixed excess of leptin signalled a gradually increasing risk for all-cause and cardiovascular mortality in patients with a large WC but an opposite effect in those with a relatively small WC. An interaction between ADPN and WC for all-cause (P = 0.01) and cardiovascular mortality (P = 0.01) emerged only in models excluding the leptin-WC interaction, suggesting that these adipokines share a common pathway leading to adverse clinical events in HD patients.. the predictive value of leptin and ADPN for all-cause and cardiovascular death in HD patients appears to be critically dependent on WC. These findings support the hypothesis that disturbances in adipokine levels are involved in adverse clinical outcomes in HD patients with abdominal obesity.

Topics: Adiponectin; Adipose Tissue; Aged; Anthropometry; Biomarkers; Cardiovascular Diseases; Epidemiologic Methods; Female; Hemodynamics; Humans; Italy; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Obesity, Abdominal; Renal Dialysis; Waist Circumference

Ghrelin abnormalities contribute to anorexia, inflammation, and cardiovascular risk in hemodialysis patients, leading to worse outcome. However, ghrelin levels are influenced by the nutritional status of the individual. We hypothesized that the consequences of ghrelin alterations in hemodialysis patients are context sensitive and dependent on the presence of protein-energy wasting (PEW). In this cross-sectional study of 217 prevalent hemodialysis patients followed for 31 months, we measured ghrelin, leptin, PEW (subjective global assessment), and C-reactive protein (an index of inflammation). Compared to patients in the middle and upper tertile of ghrelin levels, those in the lowest tertile were older, had higher leptin levels and body mass index, and presented an increased mortality risk that persisted after adjustment for age, gender, and dialysis vintage. This risk was lost after correction for comorbidities. Patients with PEW and low ghrelin values had abnormally high C-reactive protein and leptin by multivariate analysis of variance, and the highest mortality risk compared to non-PEW with high ghrelin from all-cause and cardiovascular-related mortality (adjusted hazard ratios of 3.34 and 3.54, respectively). Low ghrelin values in protein-energy wasted hemodialysis patients were linked to a markedly increased cardiovascular mortality risk. Thus, since these patients were more anorectic, our results provide a clinical scenario where ghrelin therapies may be particularly useful.

Topics: Aged; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chi-Square Distribution; Cross-Sectional Studies; Female; Ghrelin; Humans; Inflammation; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proportional Hazards Models; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Sweden; Time Factors

Inflammation and loss of appetite is the most common problem in patients with chronic kidney disease (CKD). This comparative cross-sectional study aimed to characterize the changes in circulating levels of ghrelin, obestatin, leptin, all of which have an effect on food intake, and proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in patients with CKD who were undergoing different treatments.. Study participants included 36 patients who had undergone hemodialysis (body mass index [BMI]: 22.3 ± 4.17 kg/m(2)); 41 who had undergone peritoneal dialysis (BMI: 23.5 ± 3.10 kg/m(2)), 30 with early stage CKD (BMI: 24.4 ± 3.32 kg/m(2)), and 31 healthy subjects (24.3 ± 2.14 kg/m(2)). The patients with CKD were kept under a standard diet with restricted salt, potassium, and protein intake.. Levels of leptin, acylated ghrelin, obestatin, TNF-α, and IL-6 were measured by commercially available enzyme-linked immunosorbent assay kits. Total nitrite/nitrate was analyzed using colorimetric assay kit.. Significantly high leptin levels, accompanied by low acylated ghrelin levels, were observed in patients with CKD. Maintenance dialysis did not affect these levels. TNF-α and IL-6 levels were significantly higher in CKD patients than in healthy subjects, the highest being in dialysis patients. Obestatin levels were relatively low in patients who had undergone hemodialysis.. Low acyl-ghrelin levels, accompanied with high levels of TNF-α and IL-6 may be involved in the loss of appetite and poor nutritional status in CKD patients.

Topics: Adolescent; Adult; Aged; Appetite; Body Mass Index; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Feeding and Eating Disorders; Female; Ghrelin; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nitrates; Nitrites; Nutritional Status; Renal Dialysis; Tumor Necrosis Factor-alpha; Young Adult

Chronic kidney disease (CKD) is frequently associated with malnutrition, anorexia, and hyperleptinemia. This study was designed to test the hypothesis that a component of the uremic milieu may trigger leptin release by adipocytes. To this end, mouse 3T3-L1 adipocytes were incubated for 16 hours in culture medium containing urea (80 mM) or plasma from either healthy volunteers or patients with CKD (20%, v/v). Uremic plasma and not urea induced a large release of leptin (+557%, P < .01). These results suggest that the hyperleptinemia reported in patients with CKD, could be, at least in part, because of an overproduction of leptin by the adipose tissue.

Topics: 3T3-L1 Cells; Adipocytes; Analysis of Variance; Animals; Cells, Cultured; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Mice; Middle Aged; Urea; Uremia

Dysfunction of polymorphonuclear leucocytes (PMNLs) in end-stage renal disease (ESRD) patients contributes to a diminished immune defence. The serum levels of leptin are elevated in patients with ESRD. We analysed in vitro effects of leptin on PMNLs from healthy subjects (HS; n = 12) and haemodialysis (HD) patients (n = 15) before and after HD.. PMNL oxidative burst and phagocytosis were tested by flow cytometry in whole blood. Chemotaxis of isolated PMNLs was assessed by the under-agarose method. To assess the involvement of leptin in PMNL signalling pathways, signal transduction inhibitors were used and the activity of intracellular kinases was investigated by western blotting, in vitro kinase assays and the Luminex technology.. Increasing the leptin level in the blood of HS leads to a reduced activation of the oxidative burst by Escherichia coli and phorbol 12-myristate 13-acetate. Activation of the oxidative burst is reduced in the blood of HD patients and the addition of leptin does not lead to further PMNL inhibition. Leptin at a concentration measured in HD patients significantly reduces the chemotaxis of PMNLs from HS but had no effect on PMNLs from ESRD patients before and also after HD treatment with high-flux dialysers. The phosphoinositide 3-kinase/Akt pathway is involved in the inhibitory effects of leptin.. In the presence of leptin, PMNLs from HS and HD patients respond differently to stimuli. The lack of response to leptin in PMNLs from HD patients cannot be influenced by HD.

Topics: Blotting, Western; Case-Control Studies; Chemotaxis; Female; Glucose; Humans; I-kappa B Kinase; Kidney Failure, Chronic; Leptin; Male; Neutrophils; Phagocytosis; Phosphorylation; Prognosis; Renal Dialysis; Respiratory Burst; Risk Factors; Tetradecanoylphorbol Acetate

Besides regulating energy metabolism, leptin promotes and adiponectin suppresses inflammation which is a common feature of end-stage renal disease (ESRD). Omega-3 fatty acids (n-3FA) exert anti-inflammatory actions by inhibiting pro-inflammatory signal transduction pathways whereas arachidonic acid (an n-6FA) facilitates inflammation by mediating inflammatory signals and serving as precursor of pro-inflammatory eicosanoids. Given the functional overlap between adipokines and n-3FA and n-6FA, we sought to explore their interrelationship in patients with ESRD.. 44 ESRD patients maintained on hemodialysis (HD), 29 patients receiving peritoneal dialysis (PD), and 10 healthy subjects were enrolled. Body mass index (BMI), plasma leptin, adiponectin, lipids and CRP and erythrocyte fatty acids were measured.. Compared to controls adiponectin was elevated and leptin level was reduced in the ESRD group. Adiponectin levels were comparable among PD and HD patients, but leptin and BMI were higher in PD than in HD patients. Despite comparable BMIs, female patients had higher leptin than male patients. Leptin levels were positively associations with BMI, total and LDL cholesterol whereas adiponectin was inversely related with BMI, triglycerides and CRP and directly associated with HDL cholesterol in ESRD patients. Plasma adiponectin was directly associated with erythrocyte n-3 FA (r = 0.581, p = 0.023) and inversely associated with n-6FA (r = -0.640, p = 0.010) in the HD patients.. A direct association was found between plasma levels of adiponectin and HDL and erythrocyte n-3FA in ESRD patients. Prospective trials are needed to explore the effect of n-3FA supplementation on plasma adipokines and markers of oxidative stress and inflammation in this population.

Topics: Adiponectin; Adult; Aged; Biomarkers; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Cross-Sectional Studies; Erythrocytes; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Renal Dialysis; Republic of Korea; Triglycerides

Ghrelin is involved in the pathogenesis of protein-energy wasting (PEW), inflammation, and cardiovascular complications in end-stage renal disease (ESRD). Plasma ghrelin may prove to be a powerful biomarker of mortality in ESRD but should be considered in the context of assay specificity, other weight-regulating hormones, nutritional status, systemic inflammation, and cardiovascular risk factors. ESRD patients with PEW, systemic inflammation, and low ghrelin and high leptin concentrations have the highest mortality risk and may benefit the most from ghrelin therapy.

Topics: Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Protein-Energy Malnutrition; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors

We aimed to evaluate the relationship between serum leptin and the leptin/body mass index (BMI) ratio with prevalent cardiovascular disease (CVD), and their influence on all-cause and CVD-related mortality in patients on hemodialysis (HD).. 118 stable HD patients (50 women, median [interquartile range] age, 65.1 [54.7-72.2] years) were studied. All patients had baseline measurement of serum leptin concentrations. Relationships between leptin and all-cause and CVD mortality were studied by means of survival analysis and Cox regression analysis.. The leptin/BMI ratio was similar in patients with and without CVD at baseline (0.65 [0.29-2.23] vs. 0.68 [0.29-1.49] ng·m2/ml·kg, respectively, NS). Multiple logistic regression analysis showed that there was not an independent association between leptin/BMI ratio and prevalent CVD. During the follow-up time, 52 (44.1%) patients died. CVD was the cause of death in 27 out of 52 (51.9%) deceased patients. Survival analysis and Cox proportional multivariate regression analysis showed that there were no significant relationships between leptin levels or the leptin/BMI ratio and all-cause and CVD-related mortality.. These results do not support that, in stable HD patients, serum leptin concentrations and the leptin/BMI ratio are related with prevalent CVD. Leptin/BMI ratio seems not to be a risk factor for mortality in these patients.

Topics: Aged; Body Mass Index; Cardiovascular Diseases; Cause of Death; Cohort Studies; Comorbidity; Female; Follow-Up Studies; Humans; Italy; Kaplan-Meier Estimate; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Mortality; Obesity; Proportional Hazards Models; Prospective Studies; Renal Dialysis; Risk Factors; Spain; Statistics, Nonparametric

Disturbances in the metabolism of lipoprotein profiles and oxidative stress in hemodialyzed (HD) and post-renal transplant (Tx) patients are proatherogenic, but elevated concentrations of plasma high-density lipoprotein (HDL) reduce the risk of cardiovascular disease. We investigated the concentrations of lipid, lipoprotein, HDL particle, oxidized low-density lipoprotein (ox-LDL) and anti-ox-LDL, and paraoxonase-1 (PON-1) activity in HD (n=33) and Tx (n=71) patients who were non-smokers without active inflammatory disease, liver disease, diabetes, or malignancy. HD patients had moderate hypertriglyceridemia, normocholesterolemia, low HDL-C, apolipoprotein A-I (apoA-I) and HDL particle concentrations as well as PON-1 activity, and increased ox-LDL and anti-ox-LDL levels. Tx patients had hypertriglyceridemia, hypercholesterolemia, moderately decreased HDL-C and HDL particle concentrations and PON-1 activity, and moderately increased ox-LDL and anti-ox-LDL levels as compared to the reference, but ox-LDL and anti-ox-LDL levels and PON-1 activity were more disturbed in HD patients. However, in both patient groups, lipid and lipoprotein ratios (total cholesterol (TC)/HDL-C, LDL-C/HDL-C, triglyceride (TG)/HDL-C, HDL-C/non-HDL-C, apoA-I/apoB, HDL-C/apoA-I, TG/HDL) were atherogenic. The Spearman's rank coefficient test showed that the concentration of ox-LDL correlated positively with HDL particle level (R=0.363, P=0.004), and negatively with TC (R=-0.306, P=0.012), LDL-C (R=-0.283, P=0.020), and non-HDL-C (R=-0.263, P=0.030) levels in Tx patients. Multiple stepwise forward regression analysis in Tx patients demonstrated that ox-LDL concentration, as an independent variable, was associated significantly positively with HDL particle level. The results indicated that ox-LDL and decreased PON-1 activity in Tx patients may give rise to more mildly-oxidized HDLs, which are less stable, easily undergo metabolic remodeling, generate a greater number of smaller pre-β-HDL particles, and thus accelerate reverse cholesterol transport, which may be beneficial for Tx patients. Further studies are necessary to confirm this.

Topics: Adult; Aged; Antibodies; Aryldialkylphosphatase; Atherosclerosis; Case-Control Studies; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Oxidation-Reduction; Oxidative Stress; Renal Dialysis; Risk Factors; Young Adult

The influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients.. Leptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women) with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters.. Significant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2 y; p < 0.001) with a more rapid decline in leptin levels in the highest leptin tertile in both unadjusted (p = 0.007) and fully adjusted (p = 0.047) models. A significant reduction in body composition parameters over time was observed, but was not influenced by leptin (leptin-by-time interactions were not significant). No significant associations were noted between leptin levels and changes in dietary protein or energy intake, or laboratory nutritional markers. Finally, cumulative incidences of survival were unaffected by the baseline serum leptin levels.. Thus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.

Topics: Aged; Biomarkers; Body Composition; Body Mass Index; Cross-Sectional Studies; Dietary Proteins; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Leptin; Linear Models; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Nutritional Status; Prospective Studies; Renal Dialysis; Survival Analysis

Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis

Topics: Cardiovascular Diseases; Female; Ghrelin; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Protein-Energy Malnutrition; Renal Dialysis

Leptin is a hormone secreted by adipocytes that plays an important role in regulating appetite and energy expenditure. Our aim was to evaluate serum leptin level in hemodialysis (HD) patients with or without chronic liver disease (CLD) and study the relationship between serum leptin level and bone mineral density in these groups of patients.. we recruited 20 healthy volunteers as controls (group I), 20 patients on regular HD with normal liver function (group II), 20 CLD patients with normal kidney function (group III) and 20 patients on regular HD with CLD (group IV). We measured serum calcium, phosphorus, parathyroid hormone (PTH), total alkaline phosphatase (ALP), serum leptin, 24-hours urinary hydroxyproline and bone mineral density (BMD) of the lumber spine and femoral neck by DEXA scan.. Serum leptin level was significantly higher (p < 0.001) in HD patients and CLD patients compared to controls. Its level was also significantly elevated in HD patients without liver disease (group II) compared to patients with CLD who had no renal failure (group III). Urinary hydroxyproline level was increased in both HD patients and CLD patients. We detected a positive correlation between serum leptin level and urinary hydroxyproline in all patient groups. There was a significant decrease in BMD in HD and CLD patients. BMD was significantly lower in HD patients without CLD compared to HD patients with CLD. There was a significant negative correlation between serum leptin level and BMD in CLD patients without renal disease but not in other groups (r = - 0.6, P = 0.01).. Serum leptin is elevated in HD patients with or without liver disease and in CLD patients. Serum leptin level is inversely correlated with BMD in CLD patients without renal disease.

Topics: Absorptiometry, Photon; Adult; Analysis of Variance; Bone Density; Chronic Disease; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Hydroxyproline; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Schistosomiasis; Young Adult

To evaluate the relationship between metabolic syndrome (MetS) and the fasting serum leptin concentration in hemodialysis (HD) patients.. Fasting blood samples were obtained from 101 HD patients. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation.. Forty-eight patients (47.5%) had MetS. Serum leptin concentrations were positively correlated with MetS (p<0.001). Serum leptin levels correlated with increasing numbers of MetS criteria in HD patients (p=0.001). Univariate linear regression analysis showed that the pre-HD body weight (p<0.001), waist circumference (p<0.001), body mass index (p=0.001), triglycerides (p=0.003), insulin level (p=0.043), and homeostasis model assessment of insulin resistance (p=0.003) positively correlated with serum leptin levels in HD patients and high-density lipoprotein-cholesterol (p=0.016) negatively correlated with serum leptin levels in HD patients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that pre-HD body weight (R(2)=0.175; p<0.001) was the independent predictor of the fasting serum leptin concentration.. Fasting serum leptin levels positively correlated with MetS and the pre-HD body weight could influence serum leptin in HD patients.

Topics: Aged; Body Weight; Fasting; Female; Humans; Hypertension, Renal; Insulin Resistance; Kidney Failure, Chronic; Leptin; Linear Models; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Renal Dialysis; Risk Factors

Both leptin and ghrelin (in the forms of acyl ghrelin and des-acyl ghrelin) are involved in food intake, and appear to be dysregulated in chronic kidney disease. This study describes plasma leptin, acyl, and des-acyl ghrelin concentrations in relation to protein intake and body mass index (BMI) in hemodialysis (HD) patients.. This was a cross-sectional study.. This study was conducted during the baseline phase of the French multicenter Influence of a High-Flux Dialyzer on Long-Term Leptin Levels Study.. We studied 125 HD patients (aged 72.5+/-11.7 years; 59% males).. Blood samples were collected during fasting, and before a regular HD session. Plasma ghrelin and leptin were evaluated. The protein equivalents of total nitrogen appearance and BMI were calculated.. Patients demonstrated elevated serum leptin (48.0+/-49.0 ng/mL) and des-acyl ghrelin (646.6+/-489.5 pg/mL) levels, and low acyl ghrelin levels (29.8+/-58.5 pg/mL), according to normal values. Acyl ghrelin was negatively correlated with C-reactive protein (r=-0.34, P < .001). The des-acyl to acyl ghrelin ratio was negatively correlated with protein intake, as estimated by normalized Protein Nitrogen Appearance (r=-0.22, P=.01). Serum leptin exhibited its well-described positive correlation with BMI and waist circumference, but the other hormones did not.. This study reports high des-acyl ghrelin and leptin levels and low acyl ghrelin levels in HD patients, a finding potentially associated with inflammation and food intake.

Topics: Age Factors; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; C-Reactive Protein; Dietary Proteins; Eating; Female; Ghrelin; Humans; Kidney Failure, Chronic; Leptin; Male; Renal Dialysis; Sex Factors; Waist Circumference

The aim of this study was to investigate the serum concentration of adipokines, such as leptin, adiponectin, and resistin, and assess its relation to nutritional and inflammatory parameters in both overweight and normal weight patients on maintenance hemodialysis.. A total of 36 hemodialysis patients (27 M, 9 F; mean age 55.3 +/- 12 yr.) were examined and 23 additional healthy volunteers were recruited as the control group. The concentrations of leptin, leptin receptor, adiponectin, resistin, IL-6, TNFa and CRP were measured by ELISA. Assessment of nutritional status was determined by the levels of albumin, BMI, percentage of body fat (%F), lean body mass (LBM), and Subjective Global Assessment Score (SGA).. According to the SGA 7-points score and the albumin level, 20 patients were of good nutritional status (6-7 points), while 16 patients were mildly malnourished (4-5 points). The concentrations of CRP, resistin, adiponectin, and TNFa were statistically higher in hemodialysis patients than in the control group (p pound 0.05). The adiponectin level was inversely correlated with %F (R Spearman=-0.3; p pound 0.05). The level of leptin was positively correlated with %F as well as with BMI and SGA scores (R Spearman=0.4; p pound 0.05). Although there was no significant difference in the nutritional status between the nonoverweight (BMI 18.5-24.99) and overweight (BMI (3)25.0) groups of patients, in the nonoverweight group there were 12 patients (54.5%) with signs of mild malnutrition compared to 4 malnourished patients (28.5%) in the overweight group. Nonoverweight patients presented significantly lower leptin concentration (12.7 vs 27.8 ug/l) and higher adiponectin level (38.9 vs 32.5 ng/ml) when compared to overweight patients. The levels of IL-6 and TNFa were higher in the nonoverweight group of patients. Overweight patients also had shorter durations of stay in the hemodialysis program (30.5 vs. 87.6 months).. The results of our study indicate that lean hemodialysis patients are more prone to malnutrition and inflammation. The increased levels of leptin and decreased levels of adiponectin in the overweight hemodialysis patients support the idea of a reverse epidemiology phenomenon in this group of patients.

Topics: Adipokines; Adiponectin; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Middle Aged; Nutritional Status; Overweight; Renal Dialysis; Resistin

Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality. Several studies have been published with similar results. Most of them were mainly cross-sectional and some of the prospective protocols were aimed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium, phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents. The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival.. 81 patients on hemodialysis were studied, with a wide age range and HD vintage. Several classic parameters and some less classic risk factors were studied like fetuin-A, CRP, 25-OHD and leptin. Calcifications, as Agatston scores, were evaluated with Multislice CT basally and after 12-18 months.. Coronary artery calcifications were observed in 71 of 81 patients. Non parametric correlations between Agatston scores and Age, HD Age, PTH and CRP were significant. Delta increments of Agatston scores correlated also with serum calcium, CaxP, Fetuin-A, triglycerides and serum albumin. Logistic regression analysis showed Age, PTH and serum calcium as important predictors of Delta Agatston scores. LN transformation of the not normally distributed variables restricted the significant correlations to Age, BMI and CRP. Considering the Delta Agatston scores as dependent, significant predictors were Age, PTH and HDL. A strong association was found between basal calcification scores and Delta increment at one year. By logistic analysis, the one year increments in Agatston scores were found to be predictors of mortality. Diabetic and hypertensive patients have significantly higher Delta scores.. Progression of calcification is of common occurrence, with special regard to elevated basal scores, and is predictive of survival. Higher predictive value of survival is linked to the one year increment of calcification scores. Some classic and non classic risk factors play an important role in progression. Some of them could be controlled with appropriate management with possible improvement of mortality.

Topics: Adult; Aged; alpha-2-HS-Glycoprotein; Biomarkers; Blood Proteins; C-Reactive Protein; Calcifediol; Calcinosis; Comorbidity; Coronary Disease; Diabetic Nephropathies; Disease Progression; Follow-Up Studies; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Risk Factors; Rome; Severity of Illness Index; Survival Analysis; Tomography, Spiral Computed

This cross-sectional study set out to compare total and acyl ghrelin levels in children with mild chronic kidney disease (CKD) undergoing conservative treatment (n = 19) with children with end-stage renal disease (ESRD) undergoing hemodialysis (n = 24), and with healthy controls (n = 20). The relationship between ghrelin levels and parameters of renal function, nutritional status, and selective hormones were investigated. ESRD patients had higher total ghrelin levels than those with mild CKD or control individuals. However, acyl ghrelin did not differ between groups, indicating that the excess circulating ghrelin was desacylated. Since desacyl ghrelin has been shown to inhibit appetite, increased levels might contribute to protein-energy wasting in pediatric renal patients. When all 43 renal patients were combined, multiple regression analysis found age and glomerular filtration rate (GFR) to be significant negative predictors of total ghrelin. Acyl ghrelin was influenced negatively by age and positively by energy intake. Acyl to total ghrelin ratio related positively to GFR and energy intake. The results indicate that total but not acyl ghrelin is influenced by low GFR in children with CKD and suggests that ghrelin activation may be impaired in these patients. Since energy intake is a positive predictor of acyl ghrelin, the physiological control of ghrelin secretion appears to be altered in pediatric renal patients.

Topics: Acylation; Adolescent; Biomarkers; Brazil; Child; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Energy Intake; Female; Ghrelin; Glomerular Filtration Rate; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Kidney Diseases; Kidney Failure, Chronic; Leptin; Male; Nutritional Status; Protein Processing, Post-Translational; Protein-Energy Malnutrition; Renal Dialysis; Severity of Illness Index

To investigate the effect of Shenshuai Yangzhen Capsule (SYC) on hypothalamic leptin-neuropeptide Y (NPY) and proopiomelanocortin (POMC) axes in chronic renal failure (CRF) rats with malnutrition (MN).. Forty-two male SD rats of SPF grade were established into CRF-MN model by 5/6 nephrectomy and 4% casein diet, the happening time of MN in them was recorded. Rats successfully modeled were randomized into three groups, 11 rats in Group A treated with SYC, 11 in group B treated with composite alpha-keto acid and 12 in Group C was untreated. Besides, a normal control group was set up with 8 healthy rats. After being treated for 4 weeks, the renal function related indices, including serum creatinine (Scr), blood urea nitrogen (BUN), 24 hour urine protein (24 h Upro), albumin (ALB), haemoglobin (Hb) insulin like growth factor-1 (IGF-1), total cholesterol (TC) and triglyeride (TG) were measured, and body weight, food intake in rats were observed dynamically, blood leptin and NPY level in rats were determined by radioimmunoassay; mRNA expressions of OB-Rb, NPY and POMC in hypothalamus were detected with RT-PCR.. CRF rats revealed MN at the end of 10th week after modeling. Compared with Group C, the condition of MN in Group A was significantly improved, showing increase of food intake and body weight (P < 0.05), marked improvement of renal function (P < 0.05), decrease of LP and NPY levels in plasma (P < 0.05), as well as up-regulated NPY mRNA expression and down-regulated mRNA expressions of OB-Rb and POMC in hypothalamus (P < 0.01).. SYC can improve the malnutrition condition in rats with CRF, which is possibly by way of depressing OB-Rb and POMC mRNA expression and upgrading NPY mRNA expression in hypothalamus.

Topics: Animals; Drugs, Chinese Herbal; Hypothalamus; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Neuropeptide Y; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; RNA, Messenger

To study the influence of different blood purification technology on plasma leptin and neuropeptide Y (NPY).. 150 patients with chronic renal failure in our hospital were included, which were divided into hemodialysis (HD) group, hemoperfusion (HP) group, and hemofiltration (HF) group. The serum leptin and neuropeptide Y levels were measured by radioimmunoassay (RIA) before and after first treatment, after treatment for 3, 6 month.. Serum leptin and NPY were significantly lower after HDF and HP (P < 0.05), but not after HD in single treatment and for 3, 6 months treatment (P > 0.05). Serum leptin and NPY in group HDF and HP patients in single treatment and for 3, 6 months treatment were significantly greater than those of group HD (P < 0.05). The clearance rate of leptin and NPY in group HDF and HP patients were significantly greater than those of group HD (P < 0.05). There is no correlation between serum leptin and NPY (P > 0.05).. Hemodialysis can not lower serum leptin and NPY. But HDF and HP can eliminate serum leptin and NPY preferably, which may improve the patients' nutritional status.

Topics: Adult; Aged; Aged, 80 and over; Female; Hemofiltration; Hemoperfusion; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Neuropeptide Y; Renal Dialysis

To investigate renal elimination of the adipokine fibroblast growth factor 21 (FGF21) by determining circulating FGF21 levels in patients on chronic hemodialysis (CD) as compared with control subjects with a glomerular filtration rate (GFR) >50 ml/min.. FGF21 was determined by enzyme-linked immunosorbent assay in control (n = 60) and CD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups.. Median serum FGF21 levels were >15-fold higher in CD patients (3,710.6 ng/l) than in subjects with a GFR >50 ml/min (201.9 ng/l) (P < 0.001). Furthermore, serum creatinine positively and GFR negatively predicted FGF21 concentrations in multiple regression analyses in control subjects (P < 0.05).. FGF21 serum levels increase in CD patients and are related to markers of renal function in control subjects.

Topics: Adiponectin; Adult; Aged; C-Reactive Protein; Creatinine; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast Growth Factors; Glomerular Filtration Rate; Humans; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Leptin; Male; Middle Aged; Reference Values; Renal Dialysis

The mechanism of muscle cramp in hemodialysis patients is not well understood. Leptin, a middle molecule uremic toxin, is able to affect neuronal activity. This study aimed to determine the association between leptin and hemodialysis-related muscle cramps.. A total of 79 hemodialysis patients were enrolled. The episodes of hemodialysis-related muscle cramps were recorded over a 28-day period. Serum levels of leptin were measured on the 15th day, a mid-week dialysis session.. Frequent hemodialysis-related cramps were associated with old age and elevated serum leptin levels. The risk of frequent hemodialysis-related cramps increased with increasing tertiles of leptin concentration. This relationship remained significant after adjustment for age, mean ultrafiltration ratio, gender, body mass index, insulin, resistin, c-reactive protein, albumin, peripheral arterial disease, electrolytes, and beta(2)-microglobulin.. Leptin levels are associated with frequent hemodialysis-related cramps. Further studies are necessary to elucidate the underlying mechanisms.

Topics: Aged; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Muscle Cramp; Renal Dialysis

In the general population, leptin has been associated with atherosclerosis and has been shown to interfere with lipoprotein profiles. Patients with chronic renal failure are at increased risk of cardiovascular disease and display alterations in both lipoprotein and leptin levels. The aim of this study was to investigate the relationship between leptin and the lipoprotein profile in non-dialyzed patients with chronic kidney disease (CKD).. Leptin and lipid and lipoprotein concentrations were studied in 73 CKD patients and in 68 healthy controls in a cross-sectional case-control design.. The mean leptin levels were increased in the CKD patients (24.0 (SD 37.1) ng/mL) compared to those in controls (9.0 (SD 8.5) ng/mL) (p = 0.008). Also, the ratio between leptin levels and body mass index (leptin/BMI) was increased in CKD patients (mean 0.80 (SD 1.03)) compared to that in controls (0.31 (SD 0.24)) (p = 0.001). In linear regression analysis, leptin independently predicted total cholesterol and triglycerides in CKD patients (p = 0.010 and p = 0.001, respectively) and ratio between total and HDL cholesterol (Chol/HDL) in controls (p = 0.024). Furthermore, in CKD patients, the leptin/BMI predicted the variation in total cholesterol and triglycerides (p = 0.010 and p = 0.002, respectively).. Leptin concentrations and leptin/BMI were elevated in CKD patients compared to those in controls. Leptin levels in both study groups, and leptin/BMI in the CKD group, were associated with atherogenic lipid profiles, which may contribute to the elevated cardiovascular risk that has been linked to hyperleptinaemia.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Leptin; Lipids; Lipoproteins; Male; Middle Aged

The study tested whether obese hemodialysis (HD) patients have a better nutritional and inflammatory state than those with overweight or normal body mass index (BMI).. This was a single-center, cross-sectional study.. Ninety-six stable HD patients from a local HD unit were divided into 3 groups according to BMI (normal, overweight, and obese).. Anthropometry, body composition by multifrequency bioelectrical impedance analysis, biochemical nutritional markers, as well as interleukins (IL-1, IL-6, and IL-10), tumor necrosis factor, leptin, and soluble leptin receptor (sOB-R) were measured.. Serum creatinine was significantly elevated in the highest BMI category. Albumin and transferrin were significantly elevated in higher BMI groups after adjustment for age, sex, and diabetes status. The higher BMI group had greater lean body mass (P = .001) and fat mass (P = .0001), higher phase angle (PA), and lower extracellular mass-to-body-cell-mass ratio (ECM/BCM) (P < .05). Inflammatory cytokine levels were not different in the 3 BMI groups. In parallel with increasing BMI, a gradual increase in serum leptin and a trend for decreasing sOB-R were detected (P = .0001 and P = .055, respectively). Both PA (r = 0.295, P = .008) and ECM/BCM (r = -0.345, P = .002) significantly correlated with serum leptin concentration. According to a multiple linear regression analysis, with PA as the dependent variable, age (beta = 0.274, P = .008), creatinine (beta = 0.355, P = .001), and log sOB-R/leptin ratio (beta = -0.465, P = .008) were significant independent predictors of PA.. HD patients with elevated BMI demonstrate better nutritional status compared to normal BMI or overweight patients, whereas the severity of inflammation is not related to BMI in HD patients.

Topics: Aged; Albumins; Biomarkers; Body Composition; Body Mass Index; Creatinine; Cross-Sectional Studies; Cytokines; Electric Impedance; Female; Health Status; Humans; Inflammation; Interleukins; Israel; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Renal Dialysis; Transferrin; Tumor Necrosis Factor-alpha

End-stage renal disease (ESRD) is commonly associated with anorexia, malnutrition and inflammation. In addition to serving as the primary reservoir for energy storage, adipocytes produce numerous pro- and anti-inflammatory mediators and regulate food intake by releasing the appetite-suppressing (leptin) and appetite-stimulating (adiponectin) hormones. Under normal conditions, release of leptin is stimulated by feeding to prevent excess intake, and release of adiponectin is stimulated by fasting to induce feeding. However, under certain pathological conditions such as inflammation, maladaptive release of these hormones leads to anorexia, wasting and malnutrition and simultaneously intensifies inflammation. Anorexia, malnutrition and inflammation in ESRD are frequently accompanied by hyper-leptinaemia. This study was designed to test the hypothesis that uraemic plasma may stimulate leptin release and suppress adiponectin release in normal adipocytes.. Visceral adipose tissue was harvested from normal rats, and adipocytes were isolated and incubated for 2-4 h in media containing 90% plasma from 12 ESRD patients (before and after haemodialysis) and 12 normal control subjects.. The ESRD group had a marked elevation of plasma TNF-alpha, IL-6, IL-8 and leptin concentrations before and after haemodialysis. Incubation in media containing plasma from the ESRD group elicited a much greater leptin release by adipocytes than that containing normal plasma. Post-dialysis plasma evoked an equally intense leptin release. The rise in leptin release was coupled with a parallel fall in TNF-alpha concentration in the incubation media. In contrast to leptin, adiponectin release in the presence of uraemic plasma was similar to that found with the control plasma.. Exposure to uraemic plasma induces exuberant release of leptin that is coupled with avid uptake of TNF-alpha by visceral adipocytes. These observations confirm the role of TNF-alpha, formerly known as cachexin, in the over-production and release of leptin in patients with ESRD.

Topics: Adipocytes; Adult; Animals; Cells, Cultured; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Plasma; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Uremia

Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis (PD) patients, and endothelial dysfunction (ED) is an early sign of vascular pathology. Ghrelin, a gastric peptide with CV actions, has been shown to inhibit proatherogenic changes in experimental models. However, another peptide hormone, leptin, may mediate deleterious effects on the CV system. The aim of this study is to evaluate the relationship between plasma ghrelin and leptin levels, and their association with coronary microvascular and endothelial functions in PD patients. Twenty-four (14 females and 10 males; mean age 44 +/- 12 yr) nondiabetic PD patients, between 18 and 70 years of age, were enrolled. In addition to demographic, clinical, and laboratory parameters, plasma concentrations of ghrelin and leptin were evaluated. Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurement using transthoracic Doppler echocardiography (TTDE). A CFR value of < 2 was used as an evidence for ED. When the study group was divided according to CFR measurements as CFR < 2 and >or= 2, there were no significant differences considering age, gender, etiology of renal disease, body mass index (BMI), duration of dialysis, PD modality, PD solution type, history of peritonitis, mean arterial pressure, ejection fraction, and biochemical parameters between the two subgroups. Plasma ghrelin levels (129.4 +/- 82.1 pg/mL) in patients with CFR >or= 2 were significantly higher than those in patients with CFR< 2 (63.3 +/- 35.8 pg/mL) (p = 0.03). However, no significant differences in plasma leptin levels were found between these groups [31.39 +/- 37.81 ng/mL vs. 63.95 +/- 72.83 ng/mL (p = 0.28)]. No correlation existed between plasma ghrelin levels and age, BMI, duration of dialysis, mean arterial pressure, ejection fraction, plasma leptin levels, and biochemical parameters. Decreased plasma ghrelin levels may contribute to the development of atherosclerosis in PD patients by causing ED.

Topics: Adolescent; Adult; Aged; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Endothelium, Vascular; Female; Ghrelin; Humans; Kidney Failure, Chronic; Leptin; Male; Microcirculation; Middle Aged; Peritoneal Dialysis; Ultrasonography; Young Adult

Serum levels of adipocytokines such as leptin and adiponectin are significantly elevated in patients with chronic renal failure (CRF). The effect of such adipocytokines on malnutrition in the CRF population has been of substantial interest. We sought to determine the relationship between plasma leptin and adiponectin levels and malnutrition-inflammation status in end-stage renal disease patients.. Thirty patients (15 women and 15 men; mean [+/-SD] age, 50 +/- 14 years) on hemodialysis, and 30 patients (12 women and 18 men; mean [+/-SD] age, 47 +/- 16) on continuous ambulatory peritoneal dialysis, were enrolled in this study. Adipocytokine levels were measured by enzyme-linked immunosorbent assay. Inflammatory markers, such as high-sensitivity serum C-reactive protein (hs-CRP), ferritin, and a nutritional inflammatory scoring system known as the malnutrition-inflammation score (MIS), were also measured in all patients.. Serum leptin had negative correlations with ferritin (r = -0.33, P = .016) and MIS (r = -0.39, P = .003). Adiponectin had a weak positive correlation with MIS (r = 0.26, P = .050), indicating that an increased level of serum adiponectin was associated with a worse nutritional status. Levels of hs-CRP, serum albumin, cholesterol, and triglycerides did not correlate with nutritional status.. Serum leptin concentration seems to be a marker of good nutritional status, rather than an appetite-suppressing uremic toxin, in patients with CRF. However, the positive correlation between serum adiponectin and worse nutritional-inflammatory status suggests that elevated adiponectin levels may contribute to the pathogenesis of malnutrition in such patients.

Topics: Adipokines; Adiponectin; Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Peritoneal Dialysis, Continuous Ambulatory; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin

Atherosclerotic vascular diseases such as cerebrovascular and cardiovascular diseases are major causes for fatality of hemodialysis (HD) patients. Since adipocytokines are key players for arteriosclerosis in the concept of metabolic syndrome (MetS), we aimed to determine whether circulating levels of major three adipocytokines, adiponectin, TNF-alpha, and leptin, could be associated with various parameters and clinical events in HD patients who are diagnosed as MetS using a new criteria designed for the Japanese population.. We enrolled 53 very stable patients under maintenance HD at Minami-Senju Hospital. Basically, clinical and laboratory data were taken just before HD therapy. HD sessions were performed regularly and all the participants took oral administration and injection as usual. A cross-sectional study was performed to evaluate clinical and laboratory data related to three major adipocytokines, adiponectin, TNF-alpha and leptin.. We observed no significant differences of three adipocytokines when the participants were divided in accordance with existence of MetS or past cerebrocascular/cardiovascular diseases. Only the serum adiponectin levels were significantly different in two groups categorized by existence of diabetes mellitus. Serum triglycerides (TG) were significantly correlated with two circulating adipocytokines, adiponectin (r=-0.328, p<0.016) and leptin (r=0.397, p<0.003), when we analyzed all 53 patients together.. Plasma adiponectin and leptin are expected as contributors related to dyslipidemia, suggesting these may be targets of prevention of vascular diseases in maintenance HD patients.

Topics: Adipokines; Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Metabolic Syndrome; Middle Aged; Renal Dialysis; Treatment Outcome; Triglycerides; Tumor Necrosis Factor-alpha

Our objective was to evaluate serum levels of leptin, body mass index (BMI), body-fat percentage (BF%), and insulin resistance in the first year after renal transplantation.. This study involved a prospective, observational cohort.. The setting was a transplant unit of a university teaching hospital in Porto Alegre, Brazil.. Thirty-two patients who underwent renal transplantation were prospectively followed for 1 year. A control group of 19 healthy individuals, matched by sex, age, and BMI, was included in the study.. Body mass index and BF% were measured according to anthropometric measures, serum leptin was measured by radioimmunoassay, and the homeostasis model assessment (HOMA) was used as an index of insulin resistance. Anthropometric measures and biochemical markers were evaluated prospectively, starting at transplant time and then every 3 months for up to 1 year.. Leptin levels were increased before transplantation, and decreased significantly in the first year (median, 11.9 [interquartile range, 9.2 to 25.2] to 9.3 [4.9 to 16.4] ng/mL; P < .001). The HOMA values presented a similar pattern, decreasing from 2.4 +/- 1.5 (mean +/- SD) before transplantation, to 1.5 +/- 1.1 (P = .001) at 3 months after transplantation, but increasing to 2.0 +/- 1.7 at month 12 after transplantation (P = not significant). The BMI and BF% increased significantly in the first year after transplantation (23.3 +/- 2.7 kg/m(2) vs. 24.4 +/- 2.7 kg/m(2), P = .001, and 23.71% +/- 7.79% vs. 25.63% +/- 7.68%, P = .002, respectively). According to multivariate regression analysis, HOMA levels and BF% independently predicted leptin levels after transplantation.. We found that leptin serum levels decreased significantly over the first posttransplant year. However, the effect of transplantation on insulin resistance appears to be transitory, and BF% also increases steadily in this period. The beneficial profile of leptin levels is counterbalanced by the detrimental effects of insulin resistance and BF% that may be related to the elevated cardiovascular risk observed after transplantation.

Topics: Adipose Tissue; Adiposity; Adult; Body Composition; Body Mass Index; Case-Control Studies; Cohort Studies; Female; Follow-Up Studies; Humans; Insulin Resistance; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Prospective Studies

Plasma ghrelin exerts widespread bioactivities. Although it is effectively removed from the blood by a single course of haemodialysis, peritoneal clearance of ghrelin is uncertain. Our study aimed to determine (i) whether there is a correlation between plasma ghrelin levels and characteristics of peritoneal ghrelin clearance, and (ii) whether plasma ghrelin levels significantly impact markers of mortality or morbidity in continuous ambulatory peritoneal dialysis (CAPD) patients.. We enrolled 50 qualified CAPD patients. Blood was drawn during the fasting state and 2 h post-prandially. Also during these periods, peritoneal effluents were collected for radioimmunoassay of total plasma ghrelin level and measurement of other parameters. Twenty-four hour ascites were collected for determination of ghrelin daily mass transfer.. Peritoneal ghrelin clearance was positively correlated with the dialysate-peritoneal creatinine (D/P(Cr)) ratio. Fasting plasma ghrelin levels were inversely correlated with the peritoneal/plasma (D/P(ghrelin)) ratio (P = 0.045). Plasma ghrelin levels were negatively correlated with body mass index, waist-hip ratio, fasting insulin and triglyceride level, and positively correlated with lean body mass. Plasma ghrelin levels were positively correlated with left ventricular mass (LVM), left ventricular mass index and blood pressure.. Peritoneal transporter characteristics may modulate plasma ghrelin levels in CAPD subjects. By contributing to the level of plasma ghrelin, dwelling time may have an impact on LVM and associated morbidity in CAPD patients.

Topics: Adult; Biological Transport; Body Composition; Dialysis Solutions; Female; Ghrelin; Humans; Kidney Failure, Chronic; Leptin; Lipids; Male; Middle Aged; Peptide Hormones; Peritoneal Dialysis, Continuous Ambulatory; Time Factors

The serum leptin level is elevated in patients undergoing peritoneal dialysis (PD) and associated with a loss of lean body mass. The nutritional status of PD patients may further be worsened following peritonitis. We investigated the association between hyperleptinaemia, inflammation and malnourishment in PD-related peritonitis.. We conducted a prospective study on PD patients who developed peritonitis. Blood samples were obtained as baseline (D0) before the onset of peritonitis, and once peritonitis developed, leptin, adiponectin (ADPN) and other inflammatory markers were collected, on day 1 (D1), day 7 (D7) and day 42 (D42) of peritonitis. Patients were followed-up for any censor event or 1 year after peritonitis.. Forty-two patients with a mean age of 62.9+/-13.2 years were recruited. Fourteen (33.3%) were diabetic. The serum leptin levels increased significantly from baseline to day 1 and 7, but fell back to the premorbid state at day 42. In contrast, the ADPN level decreased from a baseline value of 15.60+/-10.4 microg/ml to 13.01+/-8.1 microg/ml on day 1 (P=0.01) but rose to 14.39+/-8.9 microg/ml on day 7 (P=0.28) and 13.87+/-7.9 microg/ml on day 42 (P=0.21). High-sensitivity C-reactive protein (hs-CRP) increased significantly from baseline to day 1, 7 and even at day 42. The lean body mass (LBM) and nutritional markers decreased significantly after peritonitis. For patients with high hs-CRP (>3.0 mg/l) at day 42, there was a higher mortality rate than for those with lower hs-CRP (<3.0 mg/l, P=0.02), even if they were in clinical remission of peritonitis.. Our study confirmed an increase in serum leptin during acute peritonitis and a prolonged course of systemic inflammation after apparent clinical remission of peritonitis. These factors related to the persistent chronic inflammation may contribute to the development of malnourishment and poor survival rate.

Topics: Adiponectin; Aged; C-Reactive Protein; Chronic Disease; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Peritonitis; Predictive Value of Tests; Prognosis; Prospective Studies; Protein-Energy Malnutrition; Tumor Necrosis Factor-alpha

Little information is available on the relationship between serum resistin levels and other adipokines with serum lipid levels and insulin resistance in uremic patients under different dialysis modalities.. This study investigated the effects of dialysis modality on serum leptin, adiponectin, resistin, interleukin 6 (IL-6), and tumor necrosis factor (TNF) alpha levels in age, sex, and total adipose tissue mass (TATM); matched 30 hemodialysis (HD) patients, 30 continuous peritoneal dialysis (CAPD) patients, and 30 healthy controls; and evaluated the relationship between these adipokines and dyslipidemia and insulin resistance.. Serum resistin, adiponectin, IL-6, TNF-alpha, and high sensitive C reactive protein (hsCRP) levels were significantly increased in dialysis patients compared to controls (p < 0.05). In CAPD patients, serum leptin, resistin, triglycerides, and total cholesterol levels were higher than those in HD patients (p < 0.05). Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and low density lipoprotein (LDLc) levels in both dialysis groups. Resistin levels were found to positively correlate with TATM and triglycerides in CAPD patients. No relationship was found between the homeostasis model assessment-insulin resistance index (HOMA-IR) and adipokines studied.. Serum leptin, resistin, triglycerides, and total cholesterol levels were higher in CAPD patients. Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and LDLc levels in dialysis patients. Resistin levels were positively correlated with TATM and triglycerides in CAPD patients. Glucose load during CAPD may be an important factor in increased in leptin, resistin, triglycerides, and total cholesterol levels in CAPD patients. These results highlight the importance of leptin and resistin as determinants of dyslipidemia, especially in CAPD patients.

Topics: Adiponectin; Adipose Tissue; Adult; Blood Glucose; Body Mass Index; Female; Humans; Insulin; Interleukin-6; Kidney Failure, Chronic; Leptin; Lipids; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Reference Values; Renal Dialysis; Resistin; Tumor Necrosis Factor-alpha

We sought to determine the prevalence of hyperinsulinemia and insulin resistance in pediatric patients with chronic kidney disease (CKD) stages 2-4. Data were collected on 43 subjects, aged 6-21 years with mean glomerular filtration rate (GFR) = 47 ml/min per 1.73 m(2) body surface area. Patients were grouped by body mass index (BMI) as either non-lean (>85th percentile) or lean (

Topics: Adiponectin; Adolescent; Adult; Body Mass Index; Child; Glomerular Filtration Rate; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Kidney Failure, Chronic; Leptin; Prevalence; Regression Analysis; Tumor Necrosis Factor-alpha

Topics: Animals; Humans; Kidney Failure, Chronic; Leptin; Mice; Risk Factors

To find the association between serum leptin, blood lymphocytes and PMN percentages as markers of immune-system function, as well as nutritional status in long term hemodialysis patients.. In a group of long term hemodialysis patients, serum leptin, albumin, creatinine, BUN, and white-blood cell (WBC) count--[lymphocytes and polymorphonuclear (PMN) cells] were measured.. A significant positive correlation between serum leptin and body-mass index and between serum leptin and lymphocyte percentage was found, as well as a significant negative correlation between serum leptin and PMN percentage. There was a weak negative correlation between WBC counts and the duration and dosage of dialysis, and also a near significant negative correlation between WBC counts and hemodialysis adequacy. There was also a significant negative correlation between WBC counts and serum albumin.. Generally increased neutrophil coun and increased lymphocyte count markers of an increased mortality in hemodialysis patients. This study shows a positive association between serum leptin and lymphocytes, and a negative correlation between serum leptin and PMN. Leptin might have a protective role in decreasing mortality in hemodialysis patients by maintaining the function of the immune system (Tab. 1, Fig. 3, Ref 33).

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Kidney Failure, Chronic; Leptin; Lymphocyte Count; Male; Middle Aged; Nutritional Status; Renal Dialysis

Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD). However, its etiology is unclear. We hypothesized that the adipocyte-derived proteins leptin and adiponectin, inflammation (as measured by C-reactive protein, CRP), and insulin resistance (as measured by homeostasis model assessment, HOMA), implicated in the malnutrition-inflammation complex syndrome commonly seen in maintenance dialysis patients, would be associated with the loss of muscle mass in earlier stages of CKD. Arm muscle area was used as an indicator of muscle mass.. The Modification of Diet in Renal Disease Study cohort of people with CKD stages 3 and 4 was used for analysis (N = 780).. Regression models were carried out to examine the relationships of leptin, adiponectin, CRP, and HOMA with arm muscle area (the main study outcome).. Arm muscle area was 39 +/- 15 cm(2) (mean +/- SD), and adiponectin levels were 13 +/- 7 microg/mL. Median and interquartile range (IQR) concentrations were: 9.0 (13.6) ng/mL for leptin, 2.3 (4.9) mg/L for CRP, and 2.4 (2.0) for HOMA. Higher leptin (beta coefficient and 95% confidence interval, -6.9 [-8.7 to -5.1], P < .001) and higher CRP (beta coefficient and 95% confidence interval, -2.7 [-3.9 to -1.4], P < .001) were associated with lower arm muscle area. There was a trend toward lower arm muscle area with higher adiponectin (P = .07), but no association with HOMA (P = .80).. Leptin and CRP were associated with lower muscle mass in subjects with CKD at stages 3 and 4. Further studies are needed to understand the mechanisms underlying these associations, and to develop targeted interventions for this patient population.

Topics: Adiponectin; Adipose Tissue; Adolescent; Adult; Aged; Anthropometry; Arm; Biomarkers; Body Composition; C-Reactive Protein; Cohort Studies; Disease Progression; Female; Humans; Insulin Resistance; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Muscle, Skeletal; Nutritional Status; Prognosis; Regression Analysis; Renal Dialysis; Severity of Illness Index

Renal function affects thyroid function and adipocytokines in many ways. We aimed to assess the adipocytokines adiponectin and leptin in relation to thyroid function in patients with chronic renal failure treated conservatively, in haemodialysed patients and in kidney allograft recipients.. The study was performed on 33 patients with chronic renal failure, 64 haemodialysed patients, 54 kidney allograft recipients and 38 healthy volunteers. Thyroid volume was estimated sonographically, thyroid hormones were determined by Micropartide Enzyme Immunoassay (MEIA), and serum adiponectin and leptin were assessed by radioimmunoassay.. Serum thyroid-stimulating hormone (TSH), free T4 and free T3 were within the normal range. Adiponectin correlated significantly with free T3, haematocrit, haemoglobin, platelet count, body mass index (BMI) and urea in kidney allograft recipients. In haemodialysed patients, adiponectin correlated with free T4 and TSH, whereas leptin correlated with free T3. Multiple regression analysis showed that adiponectin was independently related only to the serum concentration of free T3 and urea in kidney transplant recipients and to free T4 and adequacy of dialysis in haemodialysed patients. In univariate analysis in patients with chronic renal failure, adiponectin correlated with free T3 and platelet count, and in healthy volunteers adiponectin correlated only with free T3 and triglycerides, and leptin correlated with BMI.. We described novel relationships between adiponectin and thyroid hormones in patients with kidney diseases. However, possible pre-existing thyroid dysfunction prior to transplantation (during dialysis therapy) and immunosuppression after transplantation make all these findings relatively complex. Therefore, the relationships between adiponectin and the thyroid axis in patients with chronic renal failure, in haemodialysed subjects or in kidney transplant recipients merit additional studies.

Topics: Adiponectin; Analysis of Variance; Case-Control Studies; Cohort Studies; Disease Progression; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Linear Models; Male; Probability; Prognosis; Reference Values; Renal Dialysis; Renal Replacement Therapy; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Thyroid Hormones

Leptin and adiponectin, well-recognized adipocytokines, are reported to contribute to the pathogenesis of atherosclerosis. The aim of this study was to elucidate the effects of icodextrin-based dialysis solution on adipocytokine metabolism.. In 12 non-diabetic anuric patients on peritoneal dialysis, dialysis solution was changed from glucose-based dialysis solution to icodextrin-based dialysis solution for 6 months. Plasma levels of leptin, adiponectin, lipids (total cholesterol, HDL-cholesterol and triglyceride), insulin, blood glucose and insulin sensitivity index by the homeostasis model assessment (HOMA-IR) were compared before and after the use of the icodextrin solution.. Plasma leptin level was decreased from 15.6 (2.5-69.0) to 7.3 (2.9-45.9) ng/ml (P = 0.018) and plasma adiponectin level increased from 11.6 (6.2-19.6) to 17.6 (7.8-33.0) microg/ml (P = 0.002). A reduction in plasma insulin level from 33.1 (13.8-54.1) to 19.1 (5.8-37.3) muU/ml (P = 0.009) and HOMA-IR from 8.22 (3.68-15.09) to 5.15 (1.40-13.78) (P = 0.015) was observed. While plasma total cholesterol level remained similar, HDL-cholesterol level increased, from 36.0 (22-45) to 43.5 (30-69) mg/dl (P = 0.008) and the triglyceride level decreased, from 174.0 (140-250) to 116.5 (81-207) mg/dl (P = 0.012).. Icodextrin-based dialysis solution improves abnormal adipocytokine metabolism, dyslipidaemia and insulin resistance, which are known to be associated with atherosclerosis. These results suggest that the use of icodextrin-based dialysis solution might be useful in preventing atherosclerosis in PD patients. Long-term effects of icodextrin-based dialysis solution on the atherosclerosis in peritoneal dialysis patients should be tested.

Topics: Adiponectin; Female; Glucans; Glucose; Hemodialysis Solutions; Humans; Icodextrin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis

Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated.. Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis).. We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61.2 +/- 1.8 years) and PD groups (n = 38, 21 men, age 54.4 +/- 1.7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects.. Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 +/- 787 vs 9280 +/- 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 +/- 216 pg/ml, P < 0.0001). Men and women showed similar serum ghrelin levels in both HD (9845.9 +/- 1071 vs 9085 +/- 1194 pg/ml) and PD patients (3214 +/- 297 vs 3250 +/- 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0.46, P < 0.05) and PD (r = 0.53, P < 0.001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found.. These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients.

Topics: Adult; Case-Control Studies; Diabetes Complications; Erythropoietin; Female; Ghrelin; Growth Hormone; Humans; Hypertension; Insulin; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Lipids; Male; Middle Aged; Peptide Hormones; Peritoneal Dialysis; Recombinant Proteins; Regression Analysis; Renal Dialysis

Topics: Body Mass Index; Drug Resistance; Erythropoietin; Humans; Kidney Failure, Chronic; Leptin

To investigate the correlation between serum leptin levels, body mass index, and triceps skin fold thickness, which are anthropometric measurements, as well as serum albumin levels in patients with chronic renal failure on hemodialysis.. We studied 75 patients (48 males, 27 females; ages between 18-82) at the Hemodialysis Unit, Cumhuriyet University Medical School; Private Sivas Dialysis Center; Hemodialysis Unit, Sultan Izzettin Keykavus Hospital; and the Hemodialysis Unit, SSK Sivas Hospital between January 2003 and February 2004. Patients were excluded if they had been on dialysis for less than one year, if they were anuric, or if they had been on dialysis with jugular or subclavian catheter and long-term permanent port catheter. Similarly, patients with diabetes mellitus, chronic pulmonary disorders, and hepatic cirrhosis or hepatitis B, hepatitis C carriers as well as those on active tuberculosis therapy were excluded. C-reactive protein was measured in all patients and those with above normal values were excluded.. While the mean age for the males was 44.52 +/- 16.53 years (18-77), it was 48.29 +/- 14.32 years (22-82) for the females. The mean triceps skin fold thickness for males was 6 +/- 1.81 mm (3-11.3 mm), and for females, it was 14.07 +/- 8.79 mm (4.3-33.3 mm). The mean body mass index for males was 20.77 +/- 2.61 kg/m2 (14.8-26.6 kg/m2), and for females, it was 25.36 +/- 6.47 kg/m2 (17.3-42.2 kg/m2). The mean serum leptin level for males was 4.61 +/- 4.20 ngr/dl (0.1-18.7 ngr/dl), and for females, it was 52.06 +/- 61.67 ngr/dl (0.6-172.5 ngr/dl). A positive correlation was observed between triceps skin fold thickness and leptin, both in the male group (r=0.478; p<0.05), and in the female group (r=0.876; p<0.05). Body mass index and leptin were also correlated positively both in the male group (r=0.502; p<0.05) and in the female group (r=0.905; p<0.05). No correlation was established between serum albumin levels and leptin. Leptin did not correlate with other measured parameters. Our study demonstrates that serum leptin levels positively correlated with body mass index and triceps skin fold thickness, which are malnutrition parameters. Therefore, the leptin hormone may be utilized in obtaining preliminary information regarding malnutrition.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Middle Aged; Renal Dialysis; Skinfold Thickness

The aim of the study was to investigate the potential relationship between left ventricular hypertrophy (LVH) and left ventricular ejection fraction with serum leptin in end-stage renal failure patients undergoing regular hemodialysis (HD) treatment.. A cross-sectional study was carried out on 41 patients (15 women, 26 men) with end-stage renal disease (ESRD), undergoing maintenance HD treatment with acetate basis dialysate and polysulfone membranes. Serum leptin, pre- and post-dialysis creatinine, predialysis BUN, calcium (Ca), phosphorus (P), serum albumin (Alb) and serum ferritin were monitorized; the patients were categorized into no LVH, mild , moderate and severe LVH, according to the performed echocardiographies.. The mean patient's age was 46+/-17.6 years. The mean length of the time patients had received HD was 29.5+/-34 months (median: 18 months). The mean serum leptin was 9.5+/-13.8 ng/mL (median value 4.7 ng/mL). In this study no significant association between stages of LVH with serum leptin was seen. In this study a significant positive correlation between LV ejection fraction with logarithm of serum leptin (r=0.32, P=0.048) (adjusted for age, duration and doses of dialysis, BMI, diabetes mellitus, serum ferritin, Ca, P and serum Alb was observed).. Leptin might not be an aggravator for LV hypertrophy. This behavior of leptin in maintenance HD patients which is in contrast to general population, especially in obese patients with normal renal function could be explained through its reverse epidemiology role in HD patients. Our results emphasize the importance of leptin in HD and clinical impact of these findings merit further investigation.

Topics: Cross-Sectional Studies; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Stroke Volume

Death rate is unacceptably elevated in end-stage renal disease patients treated with hemodialysis. Excessive body fat, or obesity, is the well-known risk factor for cardiovascular disease and other health problems in the general population. However, hemodialysis patients with a higher body mass index (BMI) have a lower risk of death, as shown by many studies. There are several explanations for the paradox of BMI in dialysis patients. First, although body mass is composed of fat mass and fat-free mass (lean mass), it is unknown which is more important, fat mass or lean mass, in predicting outcome of hemodialysis patients. Second, it is also possible that functions of adipose tissue are altered in renal failure so that accumulation of body fat leads to less atherogenicity and beneficial properties become predominant. Third, an increased fat mass may be protective against death after harmful events. In this article, we explore these possibilities using either the data of our own cohort of hemodialysis patients or the existing registry data of Japan. We conclude that in hemodialysis patients, fat mass rather than lean mass plays a protective role against mortality, that the fat mass-adipocytokine relationship is altered, and that a low BMI is associated with increased risk of fatality after cardiovascular events rather than the risk of occurrence of such events.

Topics: Adiponectin; Adipose Tissue; Body Composition; Body Mass Index; Cardiovascular Diseases; Cytokines; Humans; Kidney Failure, Chronic; Leptin; Renal Dialysis; Retrospective Studies; Risk Factors

Leptin is involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Although hypoleptinemia characterizing malnutrition has been strictly related to increased susceptibility to infection, other hyperleptinemic conditions, such as end-stage renal disease (ESRD), are highly susceptible to bacterial infections. On the other hand, ESRD is characterized by neutrophil functional defects crucial for infectious morbidity, and several uremic toxins capable of depressing neutrophil functions have been identified. In the present study, we investigated leptin's effects on neutrophil function. Our results show that leptin inhibits neutrophil migration in response to classical chemoattractants. Otherwise, leptin is endowed with chemotactic activity toward neutrophils. The two activities, inhibition of the cell response to chemokines and stimulation of neutrophil migration, could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca2+]i mobilization, oxidant production, or beta2-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties but capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. This effect is dependent on the activation of intracellular kinases involved in F-actin polymerization and neutrophil locomotion. Indeed, p38 mitogen-activated protein kinase (MAPK) and Src kinase, but not extracellular-regulated kinase (ERK), were activated by short-term incubation with leptin. Moreover, p38 MAPK inhibitor SB203580 and Src kinase inhibitor PP1, but not MEK inhibitor PD98059, blocked neutrophil chemotaxis toward leptin. Serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionine-leucyl-phenylalanine (FMLP) with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. The serum inhibitory activity can be effectively prevented by immune-depletion of leptin. Taking into account the crucial role of neutrophils in host defense, we show that leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears to be a mechanism contributing to neutrophil dysfunction in ESRD.

Topics: Chemotaxis, Leukocyte; Humans; Kidney Failure, Chronic; Leptin; Neutrophils; p38 Mitogen-Activated Protein Kinases; Serum; src-Family Kinases

To study anorexia in chronic renal failure (CRF) patients, we measured appetite-related hormones in seven CRF patients and four controls. Plasma concentrations and fractional changes from baseline (values from day 1, 0800) are listed as control vs. CRF (means +/- SE). Leptin, although higher in CRF (5.6 +/- 1.7 and 34 +/- 17 ng/ml), was suppressed after fasting; decrements were -51 +/- 9 and -55 +/- 8%. Nocturnal surge present during feeding was abolished upon fasting in both groups. Neuropeptide Y (NPY) was elevated in CRF (72 +/- 12 vs. 304 +/- 28 pg/ml, P = 0.0002). NPY rhythm, reciprocal to that of leptin, was muted in CRF. Basal cortisol was similar in both groups (17 +/- 3 and 17 +/- 2 microg/dl). In the controls, cortisol peaked in the morning and declined in the evening. CRF showed blunted cortisol suppression. Decrements were -61 +/- 3 and -20 +/- 9% at 1800 on day 1 (P = 0.008) and -61 +/- 8 and -26 +/- 8% at 2000 on day 2 (P = 0.02). Basal ACTH (25 +/- 5 and 54 +/- 16 pg/ml) as well as diurnal pattern was not statistically different between the groups. Baseline insulin was 6 +/- 1 and 20 +/- 9 microU/ml. During fasting, insulin was suppressed to -64 +/- 10 and -51 +/- 9%, respectively. Upon refeeding, increments were 277 +/- 96 and 397 +/- 75%. Thus, in our CRF patients, anorexia was not due to excess leptin or deficient NPY. Impaired cortisol suppression should favor eating. Insulin suppression during fasting and secretion after feeding should enhance both eating and anabolism. The constant high NPY suggests increased tonic hypersecretion.

Topics: Adrenocorticotropic Hormone; Adult; Appetite; Blood Glucose; Eating; Fasting; Female; Humans; Hydrocortisone; Insulin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Neuropeptide Y

Ghrelin is an acylated peptide stimulating secretion of the growth hormone (GH). It was originally isolated from the rat stomach as an endogenous ligand for the growth hormone secretagogue receptor. Although being predominantly produced by endocrine cells of the gastric fundus, its secretion has been found in various tissues including the kidney. To study the influence of renal failure on plasma ghrelin levels we examined 16 patients with end-stage renal disease (ESRD) receiving hemodialysis (8 men and 8 women) and 19 controls (10 men and 9 women). Both groups were comparable in age and BMI. In all subjects we assessed plasma levels of ghrelin, leptin, soluble leptin receptor, insulin, IGF-I, IGFBP-1, IGFBP-3 and IGFBP-6. Ghrelin levels were significantly higher in the group of dialyzed patients (4.49+/-0.74 vs. 1.79+/-0.15 ng/ml; p<0.001). These patients had significantly higher levels of GH, IGFBP-1, IGFBP-6, leptin and percentage of body fat (p<0.05). In the group of patients with ESRD plasma ghrelin levels positively correlated with IGFBP-1 (p<0.01). In the control group, ghrelin positively correlated with GH concentrations (p<0.01) and negatively correlated with the levels of insulin and creatinine (p<0.05). In conclusion, patients with ESRD have higher ghrelin concentrations, which might be caused by a decreased excretion/metabolism of ghrelin in the kidney during renal failure.

Topics: Aged; Body Composition; Creatinine; Female; Ghrelin; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Protein 6; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peptide Hormones; Receptors, Cell Surface; Receptors, Leptin; Renal Dialysis

High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease.. We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54.4 +/- 1.8 years) or HD (n = 38, 22 males and 16 females, age 60.8 +/- 1.6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history.. PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28.7 (13.0-71.9) microg/l] than those found in patients on HD [9.7 (4.7-31.9) microg/l, P < 0.01] or in conservative management [5.9 (4.3-38.6) microg/l, P < 0.05]. Adiponectin concentrations were similar in the three groups of patients (mean +/- SEM, 48.0 +/- 4.5 mg/l in PD, 57.7 +/- 4.4 mg/l in HD, and 44.4 +/- 7.0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26.3 +/- 0.99 and 27.5 +/- 1.4 microg/l, respectively, vs. 17.3 +/- 1.0 microg/l, P < 0.001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0.287, P < 0.01) and adiponectin levels were negatively related to BMI (r = -0.416, P < 0.001) and the homeostatic model assessment (HOMA-R) index (r =-0.216, P < 0.05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1.80 (1.03-3.15), P = 0.039] was found when analysing subgroups of patients.. These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.

Topics: Adiponectin; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Female; Hormones, Ectopic; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Regression Analysis; Renal Dialysis; Resistin

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.

Topics: Adiponectin; Adipose Tissue; Body Composition; Body Mass Index; Cholesterol, HDL; Female; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Sex Characteristics; Triglycerides

Malnutrition and loss of appetite remain a frequent problem in children with chronic renal failure (CRF). Recent studies in human gave much attention for leptin, polypeptide produced by adipocytes, and its influence on appetite and energetic balance regulation. The study aimed at evaluation of serum leptin levels (SLL) in children with CRF with regard to applied method of treatment. Study included 29 children, mean age 13.9 +/- 4.2 years. Among them 10 on peritoneal dialysis (PD, mean age 11.9 +/- 4.3 years), 10 - on maintenance hemodialysis (HD, mean age 16.3 +/- 2.4 years), 9 - on conservative treatment of CRF (CT, 13.0 +/- 4.3 years). SLL was evaluated by RIA. In all groups of children with CRF SLL was high: group I (PD): 34.3 +/- 44.0, group II (HD): 31.5 +/- 57.4, group III (CT): 16.5 +/- 21.1 ng/ml. There was no difference of SLL in children with CRF regarding to method of treatment. Evaluated SLL/BMI index (body mass index) showed no difference in comparison of examined groups of children with CRF (values respectively: PD: 1.5 +/- 1.8; HD: 1.3 +/- 2.1; CT: 0.8 +/- 1.9 ng/ml +/- kg/m2). Also SLL/creatinine index did not differ between examined groups (values respectively: PD: 5.2 +/- 8.2; HD: 4.4+/-8.4; CT: 4.0 +/- 4.6 ng/mg). In both subgroups on dialysis treatment SLL correlated with BMI, additionally in HD SLL correlated with body weight, in PD - with serum ionised calcium. No correlation with age, dialysis treatment duration, creatinine and urea levels was found.. In children on maintenance dialysis high SLL were observed. The highest SLL in PD patients, when considering CRF group could be related to high dialysate glucose concentration and probably decreased clearance through the peritoneal membrane. The correlation between SLL and BMI was preserved in all groups of children with CRF, irrespective of applied method of treatment.

Topics: Adolescent; Adult; Body Mass Index; Child; Child, Preschool; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Nutrition Disorders; Nutritional Status; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

Dose requirements of epoetin vary considerably among patients with end-stage renal disease (ESRD), whereas determinants of epoetin sensitivity are poorly understood. Fat mass is an important source of adipokines, including interleukin 6 (IL-6), which is associated with decreased epoetin sensitivity. Furthermore, the adipokine leptin stimulates human erythroid development in vitro. In the present study, we investigate the impact of fat mass and leptin level on epoetin sensitivity in patients with ESRD.. One hundred sixty-six patients with ESRD (107 men; 64%) with a mean age of 56.9 +/- 0.9 years were studied in a post hoc cross-sectional analysis. Body composition was analyzed by dual-energy X-ray absorptiometry and correlated with serum markers of inflammation and leptin (analyzed by enzyme-linked immunosorbent assays), as well as with epoetin dose, in international units administered per week (IU/wk). To correct for differences in body mass and hemoglobin (Hb) levels, epoetin sensitivity was approximated as epoetin/Hb ratio, ie, epoetin dose per unit of Hb (IU/wk/g/dL) and epoetin/Hb/kg ratio, ie, epoetin dose per unit of Hb and kilogram of patient body weight (IU/wk/Hb/kg).. Patients were divided into 3 groups according to epoetin/Hb/kg ratio (no-epoetin group, low-epoetin group, and high-epoetin group). The 3 groups had significantly different serum levels of high-sensitivity C-reactive protein (hsCRP; median, 8.6 versus 3.1 and 8.0 mg/L, respectively; P < 0.05), neopterin (median, 112.4 versus 94.3 and 96.1 ng/L, respectively; P < 0.05), and IL-6 (median, 6.8 versus 4.1 and 6.5 ng/mL, respectively; P < 0.05). Significant between-group differences also were found in fat mass and leptin levels (median, 14.8 versus 10.5 and 7.9 ng/mL, respectively; P = 0.02). In univariate analyses, significant relationships between epoetin sensitivity indices, leptin levels, and levels of the inflammatory markers hsCRP and IL-6 were found. In a multivariate stepwise regression model, log ferritin, parathyroid hormone, log leptin, log IL-6, and polycystic kidney disease were significantly associated with the epoetin/Hb ratio.. The present study shows that leptin level may be a predictor of epoetin sensitivity. The effect could be either direct stimulation of erythropoiesis or indirect stimulation by associated adipokines. Although truncal fat is associated with secretion of proinflammatory cytokines, this secretion appears not to have inhibitory effects on epoetin sensitivity in the presence of high leptin levels.

Topics: Adipose Tissue; Anemia; Body Composition; C-Reactive Protein; Cross-Sectional Studies; Darbepoetin alfa; Drug Resistance; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Inflammation; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Organ Size; Polycystic Kidney Diseases; Renal Dialysis; Sweden

Hypotension is an important complication of hemodialysis. The pathogenesis of this complication remains unclear. The role of chronic inflammation in chronic dialysis-associated hypotension has not been investigated. A total of 38 dialysis patients with chronic hypotension were identified. Their demographic and biochemical data, inflammatory markers (high sensitivity C-reactive protein [hs-CRP] and interleukin-6 [IL-6]), hepatocyte growth factor (HGF), leptin, and adiponectin levels were measured and compared with those of another 87 nonhypotensive dialysis patients. No between-group differences in their clinical features, underlying renal disease were found. Levels of serum albumin, leptin, adiponectin, and HGF were similar between the two groups. The serum albumin levels were inversely correlated with hs-CRP and IL-6. Adiponectin was negatively correlated with hs-CRP and leptin. HGF showed a positive relation with hs-CRP. No association was found between adiponectin and HGF. Therefore, chronic inflammation is prevalent in the dialysis population, and serum HGF level is associated with inflammation but not with chronic dialysis hypotension.

Topics: Adiponectin; Biomarkers; C-Reactive Protein; Female; Hepatocyte Growth Factor; Humans; Hypotension; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Serum Albumin

Leptin is a protein hormone secreted by adipocytes, regulating body fat and food intake. It has been reported that serum leptin levels are high in patients with chronic renal failure, and this fact has been associated with malnutrition and body composition changes in patients on hemodialysis. This present study investigated the relationship between plasma leptin concentrations and body composition and markers of malnutrition in nondiabetic patients diagnosed with end-stage chronic renal failure, treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD).. A total of 152 HD and 32 CAPD patients were enrolled into the study. The body compositions of the patients were established by utilizing a Body Composition Analyzer. Triceps skinfold thickness (TSFT) was measured by using a Harpenden Skinfold Caliper. Serum leptin level was detected by radioimmunoassay in ng/mL through employing a DPC Gambyt-CR gamma counter. Standard laboratory methods were used for measuring the remaining parameters (total protein, albumin, blood urea nitrogen, creatinine, hemoglobin, hematocrit, high-sensitivity C-reactive protein [hsCRP]).. No significant difference was observed between the HD and CAPD groups regarding leptin levels. Leptin levels of female patients in both groups were markedly higher when compared with those of men (p = 0.001). Plasma leptin levels in total, as well as for both male and female HD and CAPD patients, significantly correlated positively with age, percent fat, fat mass, body mass index and TSFT (p = 0.001). Serum leptin levels were not found to be correlated with length of time on dialysis, lean body mass, total body water, hsCRP, total protein and albumin levels (p > 0.05).. The data obtained in this study indicated that serum leptin levels could be instrumental markers in establishing body fat ratio, as well as in determining metabolic and nutritional factors in patients with chronic renal failure.

Topics: Adult; Aged; Biomarkers; Body Composition; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Malnutrition; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis

To analyze the changes in IGF-1, IGFBP-3, leptin and insulin after replacement doses of recombinant human growth hormone (rhGH) in short prepubertal children with chronic renal failure (CRF).. Eleven children (3F:8M), with mean age of 9.6 years, were treated with rhGH (0.23 mg/Kg weekly for 12 months). Serum leptin, insulin, glucose, IGF-1 and IGFBP-3 were measured before, 6 and 12 months after beginning rhGH treatment.. The serum levels of leptin, insulin and glucose did not vary during the treatment; normal leptin and glucose levels and high insulin were observed. There was a significant increment of IGF-1 and IGFBP-3 during the use of rhGH.. The replacement doses of rhGH during 12 months in a selected group of CRF children determined an increment in IGF-1 and IGFBP-3, associated to normal serum leptin and insulin resistance.

Topics: Body Composition; Body Height; Child; Electric Impedance; Enzyme-Linked Immunosorbent Assay; Female; Hormone Replacement Therapy; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Statistics, Nonparametric; Time Factors

We have used serial visual analogue scores to demonstrate disturbances of the appetite profile in dialysis patients. This is potentially important as dialysis patients are prone to malnutrition yet have a lower nutrient intake than controls. Appetite disturbance may be influenced by accumulation of appetite inhibitors such as leptin and cholecystokinin (CCK) in dialysis patients.. Fasting blood samples were drawn from 43 controls, 50 haemodialysis (HD) and 39 peritoneal dialysis (PD) patients to measure leptin and CCK. Hunger and fullness scores were derived from profiles compiled using hourly visual analogue scores. Nutrient intake was derived from 3 day dietary records.. Fasting CCK was elevated for PD (6.73 +/- 4.42 ng/l vs control 4.99 +/- 2.23 ng/l, P < 0.05; vs HD 4.43 +/- 2.15 ng/l, P < 0.01). Fasting CCK correlated with the variability of the hunger (r = 0.426, P = 0.01) and fullness (r = 0.52, P = 0.002) scores for PD. There was a notable relationship with the increase in fullness after lunch for PD (r = 0.455, P = 0.006). When well nourished PD patients were compared with their malnourished counterparts, CCK was higher in the malnourished group (P = 0.004). Leptin levels were higher for the dialysis patients than controls (HD and PD, P < 0.001) with pronounced hyperleptinaemia evident in some PD patients. Control leptin levels demonstrated correlation with fullness scores (e.g. peak fullness, r = 0.45, P = 0.007) but the dialysis patients did not. PD nutrient intake (energy and protein intake, r = -0.56, P < 0.0001) demonstrated significant negative correlation with leptin.. Increased CCK levels appear to influence fullness and hunger perception in PD patients and thus may contribute to malnutrition. Leptin does not appear to affect perceived appetite in dialysis patients but it may influence nutrient intake in PD patients via central feeding centres.

Topics: Adult; Aged; Appetite; Appetite Regulation; Cholecystokinin; Dialysis; Diet Records; Eating; Feeding Behavior; Female; Humans; Hunger; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Satiation

The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD.. In a cohort of 204 (62% males) ESRD patients aged 52 +/- 1 years the following parameters were studied: presence of CVD, body composition, plasma adiponectin (N= 107), cholesterol, triglycerides, HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in the apM1 gene at positions -11391, -11377, 45, and 276. Thirty-six age- (52 +/- 2 years) and gender-matched (64% males) healthy subjects served as control subjects.. Markedly (P < 0.0001) elevated median plasma adiponectin levels were observed in ESRD patients (22.2 microg/mL), especially type 1 diabetic patients (36.8 microg/mL), compared to control subjects (12.2 microg/mL). Log plasma adiponectin correlated to visceral fat mass (R=-0.29; P < 0.01) and Log hs-CRP (R=-0.26; P < 0.01). In a stepwise (forward followed by backward) multiple regression model only type-1 diabetes (P < 0.001) and visceral fat mass (P < 0.05) were independently associated with plasma adiponectin levels. The adiponectin gene -11377 C/C genotype was associated with a lower prevalence of CVD (25 vs. 42%) compared to the G/C genotype.. The present cross-sectional study demonstrates that, whereas genetic variations seem to have a minor impact on circulating adiponectin levels, lower visceral fat mass and type 1 diabetes mellitus are associated with elevated plasma adiponectin levels in ESRD patients. Furthermore, low levels of adiponectin are associated with inflammation in ESRD.

Topics: Adiponectin; Albuminuria; Biomarkers; Body Composition; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus, Type 1; Female; Fibrinogen; Genetic Variation; Glomerular Filtration Rate; Humans; Intercellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Leptin; Lipids; Male; Middle Aged; Phenotype; Proteins

Leptin is an adipocyte hormone important in appetite, energy homeostasis, neuroendocrine and haematopoietic function. Patients with renal failure often have elevated total and free leptin levels. Biologically active leptin fragments (leptin(22-56) and leptin(57-92)) have been identified, but whether these fragments are affected by renal failure and/or haemodialysis (HD) is not known.. Leptin, leptin(22-56) and leptin(57-92) levels were measured in 28 HD patients [14 men, 14 women, age 45.5 +/- 16.4 years, body mass index (BMI) 23.8 +/- 3.6 kg/m2] and 25 healthy controls with similar age and BMI. In 18 HD patients, leptin and fragment levels were measured before and after 2 consecutive dialysis treatments and on the intermediate, dialysis-free day.. Baseline leptin levels were higher in HD patients vs. controls (69.3 +/- 62.2 ng/ml vs. 30.4 +/- 32.7, P < 0.02) as were leptin(22-56) (7.14 +/- 7.04 ng/ml vs. 1.86 +/- 1.84, P < 0.02) and leptin(57-92) (5.94 +/- 6.08 ng/ml vs. 1.58 +/- 1.98, P < 0.02). Baseline leptin and fragment levels correlated significantly and independently with BMI in HD patients (r = 0.70, r = 0.59, r = 0.72, respectively, P < 0.001). After each HD session, leptin levels were reduced to levels not different from controls, but increased on the intermediate, dialysis-free day. Similar to and independently from total leptin, both leptin fragments were reduced after the first HD session to levels not different from controls. The reduction in leptin levels was higher with synthetic vs. cellulosic membrane types (37.7 +/- 23.5%vs. 18.1 +/- 21.8%, P < 0.03). Leptin correlated weakly with the erythropoietin to haematocrit ratio (T = -0.20, P = 0.14), while leptin(22-56) had a significant negative correlation with this index (T = -0.42, P < 0.01), suggesting that this fragment may favour haematopoiesis.. Leptin fragments are detected in human serum, and both leptin and leptin fragments correlate with BMI, are significantly elevated in HD patients compared to controls, and are significantly decreased by haemodialysis. The elevated leptin fragments may have important physiological significance for the anorexia, hypogonadism, and anaemia commonly seen in HD patients, but this remains to be conclusively shown by interventional trials.

Topics: Adult; Analysis of Variance; Body Mass Index; Case-Control Studies; Female; Hematopoiesis; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peptide Fragments; Precipitin Tests; Renal Dialysis

To examine the changes of expressions of orexin A, orexin receptor-1 (OX1R), prepro-orexin (Prepro-OX) mRNA, OX1R mRNA and ob-R of hypothalamus in rats with chronic renal failure (CRF).. Sixty-two male Wister rats weighing 200-250 g were divided into three groups, including group 1 (normal, n = 5), group 2 (sham-operated, n = 25) and group 3 (CRF, n = 32). Hypothalamus orexin A was assayed by radioimmunoassay. Serum leptin was assayed by enzyme linked immunosorbent assay. The expression of Prepro-OX mRNA and OX1R mRNA of hypothalamus were measured by reverse transcription polymerase chain reaction, and expression of orexin A, OX1R and ob-R by immunohistochemistry. Automatic biochemical analyzer was used to measure the serum creatinine.. Hypothalamus orexin A levels were negatively correlated (r = -0.63, P < 0.001) with serum leptin levels in the rats. The expression of hypothalamus Prepro-OX mRNA in CRF rats was significantly lower than that of sham-operation at week 12 (P < 0.01). Hypothalamus Prepro-OX mRNA levels were negatively correlated (r = -0.81, P < 0.001) with the levels of serum leptin and serum creatinine (r = -0.68, P < 0.05) in the rats at week 12. The expression of hypothalamus OX1R mRNA in CRF rats was lower than that of sham-operation at week 12 (P > 0.05). Specific immunoreactivity for orexin A was present in perikeryon of the hypothalamus neuron. Specific OX1R-like immunoreactivity was observed in some nerve fibres. Specific immunoreactivity for ob-R was present in membranes of the hypothalamus neuron. Hypothalamus neurons of orexin A-like specific immunoreactivity in CRF rats were significantly fewer than those in shamoperated rats at week 8. Hypothalamus neurons of OX1R-like specific immunoreactivity in CRF rats were similar to those in sham-operated rat at week 8. Hypothalamus neurons of ob-R-like specific immunoreactivity in CRF rats were significantly more than those in sham-operated rats at week 8.. The lower hypothalamus orexin A levels may be induced by high serum leptin level in CRF rats. The lower expression of hypothalamus Prepro-OX mRNA in CRF rats may be one of the main causes inducing lower hypothalamus orexin A. The expression of OX1R in hypothalamus neurons is somewhat reduced and the expression of ob-R in hypothalamus neurons is somewhat raised in CRF rats. These remain to be studied further.

Topics: Animals; Carrier Proteins; Hypothalamus; Intracellular Signaling Peptides and Proteins; Kidney Failure, Chronic; Leptin; Male; Neuropeptides; Neurotransmitter Agents; Orexin Receptors; Orexins; Protein Precursors; Random Allocation; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Leptin; Receptors, Neuropeptide; RNA, Messenger

Serum leptin levels are elevated in patients with kidney failure. Data on the associations of serum leptin and on the relationship of leptin with both kidney function and inflammation, are limited in patients with reduced glomerular filtration rate (GFR). We evaluated the independent associations of serum leptin in patients with reduced GFR.. Serum leptin and C-reactive protein (CRP) were measured in samples from 798 participants of the Modification of Diet in Renal Disease Study. Multivariable analysis was used to evaluate the independent effects of kidney function and CRP on leptin levels.. Median (interquartile range) of serum leptin was 9.1 ng/ml (14.0). Female gender, higher percent body fat, higher insulin levels, older age, lower GFR and higher CRP were associated with higher serum leptin levels and explained 51% of the variability in the logarithm of serum leptin levels. After adjusting for the other variables, a 10 ml/min/1.73 m2 lower GFR was associated with 6% higher mean serum leptin levels. Percent body fat and gender, explained 45% of the variability in serum leptin levels.. Level of kidney function and CRP are associated with serum leptin in patients with reduced GFR. However, there is a stronger association between serum leptin and indices of body fat and gender in patients in the earlier stages of chronic kidney disease. 50% of the variability remains unexplained in patients with reduced GFR.

Topics: Body Mass Index; C-Reactive Protein; Female; Glomerular Filtration Rate; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Multivariate Analysis; Sex Factors

Topics: Anorexia; Body Mass Index; Energy Intake; Feeding Behavior; Humans; Kidney Failure, Chronic; Leptin; Malnutrition; Peritoneal Dialysis; Renal Dialysis

Hyperleptinemia is a common feature in hemodialysis (HD) patients. However, the role of increased serum leptin levels in the pathogenesis of HD-related anorexia is still controversial. The purpose of the present prospective study was to ascertain whether hyperleptinemia is causally implicated in the pathogenesis of HD-related anorexia.. We measured the serum leptin levels and the serum leptin/body mass index (BMI) ratio in 24 healthy subjects and in 49 end-stage renal disease patients on maintenance HD. HD patients were subdivided into anorexic (14/49, 28.5%) and non-anorexic (35/49, 71.5%) according to a questionnaire discriminating for the presence of anorexia-related symptoms.. Calorie (kcal/kg/day) and protein (g/ kg/day) intakes were significantly lower in anorexic than in non-anorexic patients (20.1 +/- 1.1 vs. 27.9 +/- 1.3, p = 0.004, and 0.82 +/- 0.05 vs. 1.19 +/- 0.05, p = 0.001, respectively). Accordingly, serum albumin, total lymphocyte count, mid-arm muscle circumference, and the protein equivalence of nitrogen appearance (PNA) were significantly lower in anorexic patients. The serum leptin concentration (ng/ml) was significantly higher in HD patients than in controls, in males (15.33 +/- 3.4 vs. 3.7 +/- 0.3, p = 0.003) and in females (42.3 +/- 7.2 vs. 10.5 +/- 1.3, p = 0.03). Similarly, serum leptin/BMI ratio was significantly higher in HD patients than in controls, in males (0.56 +/- 0.1 vs. 0.16 +/- 0.02, p = 0.0028) and in females (1.8 +/- 0.2 vs. 0.4 +/- 0.04, p < 0.0001). However, serum leptin levels were similar in anorexic and in non-anorexic patients, in males (15.3 +/- 5.6 vs. 16.9 +/- 4.2, p = 0.85) and in females (46.6 +/- 12.9 vs. 47.4 +/- 9.4, p = 0.96). No differences were observed between the 2 groups in the serum leptin/BMI ratio, in males (0.59 +/- 0.2 vs. 0.58 +/- 0.14, p = 0.92) and in females (1.5 +/- 0.4 vs. 1.8 +/- 0.3, p = 0.94). Similarly, no statistically significant differences in terms of serum leptin levels and leptin/BMI ratio were observed between patients with dietary energy intake of <30 or > or =30 kcal/kg/day and between those with a dietary protein intake of <1.2 or > or =1.2 g/kg/day. No significant correlations were found between serum leptin levels and PNA, albumin, cholesterol, total lymphocytes number, weight change, C-reactive protein, fibrinogen, ferritin, and complement.. The present results indicate that mechanisms other than increases in serum leptin levels might be involved in the pathogenesis of HD-related anorexia.

Topics: Aged; Anorexia; Blood Proteins; Body Mass Index; Case-Control Studies; Cholesterol; Comorbidity; Dietary Proteins; Energy Intake; Female; Humans; Kidney Failure, Chronic; Leptin; Leukocyte Count; Male; Malnutrition; Middle Aged; Renal Dialysis; Surveys and Questionnaires

Leptin is a pleiotropic molecule involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Hypoleptinemia characterizing starvation has been strictly related to increased susceptibility to infection secondary to malnutrition. Nevertheless, ESRD is characterized by high susceptibility to bacterial infection despite hyperleptinemia. Defects in neutrophils play a crucial role in the infectious morbidity, and several uremic toxins that are capable of depressing neutrophil functions have been identified. Only a few and contrasting reports about leptin and neutrophils are available. This study provides evidence that leptin inhibits neutrophil migration in response to classical chemoattractants. Moreover, serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. Finally, the serum inhibitory activity can be effectively prevented by immune depletion of leptin. The results also show, however, that leptin by itself is endowed with chemotactic activity toward neutrophils. The two activities-inhibition of the cell response to chemokines and stimulation of neutrophil migration-could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca(2+)](i) mobilization, oxidant production, or beta(2)-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties that are capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. Taking into account the crucial role of neutrophils in host defense, the leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears as a potential mechanism that contributes to the establishment of infections in ERSD.

Topics: Chemotaxis, Leukocyte; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Neutrophils; Toxins, Biological; Uremia

Chronic renal failure (CRF) provokes derangement in various hormonal regulations of food intake and energy expenditure. In the present study, we have examined the effect of a low protein, low phosphorus diet on circulating levels of leptin, tumour necrosis factor (TNF)-alpha, and insulin in patients with CRF.. Seventeen male, non-diabetic subjects with conservatively treated CRF (estimated creatinine clearance 39.5 +/- 11.1 mL/min), and proteinuria below 2 g/day were prospectively studied. Measurements of hormonal, metabolic and anthropometric parameters were performed before and after 16 weeks of dietary treatment (protein 0.6 g/kg of ideal body mass, 30% of calories derived from fat, 62% of calories derived from carbohydrates and 10 mg/kg of phosphorus). Actual dietary intake in patients was measured by using 3-day food records and was supervised by the dietician.. Body mass index and body fat mass remained unchanged during the 4 months of dietary treatment. Urea, leptin, and TNF-alpha serum concentrations decreased significantly.. A low protein, low phosphorus diet reduces TNF-alpha and leptin levels in plasma. The effect on leptin appears not to be mediated by an insulin-dependent mechanism.

Topics: Adult; Aged; Diet, Protein-Restricted; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prospective Studies; Tumor Necrosis Factor-alpha

Non-dialysed chronic kidney disease (CKD) patients may have altered resting energy expenditure (REE) because of the important metabolic functions of the kidneys. The aim of the present study was to evaluate whether REE in clinically stable, non-diabetic and non-dialysed CKD patients with no clinical signs of inflammation, was different from that of gender and age pair-matched healthy controls. Subjects and methods. REE in 45 patients (20 male and 25 female; age 44.9 +/- 11.7 years; mean +/- SD) and 45 healthy individuals (20 male and 25 female; age 44.6 +/- 11.5 years) was measured by indirect calorimetry after a 12-h fast. In both groups, body composition was assessed by bioelectrical impedance. Glomerular filtration rate was assessed by creatinine clearance only in the CKD patients.. The mean creatinine clearance and serum creatinine of the CKD patients were 29.1 +/- 14.6 ml/min/1.73 m(2) and 3.48 +/- 2.48 mg/dl, respectively. Body fat (BF) and lean body mass (LBM) were similar between the two groups (CKD patients: BF 28.6 +/- 11.3%, LBM 46.9+/-10.0 kg; and healthy individuals: BF 28.1 +/- 7.54%, LBM 49.5 +/- 10.5 kg). REE of CKD patients was significantly lower than that of healthy individuals (1325 +/- 206 vs 1448 +/- 258 kcal/day; P = 0.01, respectively) even after adjusting for LBM by multiple regression analysis. In fact, the presence of chronic renal insufficiency reduced REE by 103.2 kcal/day (P = 0.02; 95% confidence interval (-15.9; 190.5)).. REE of clinically stable non-dialysed, non-diabetic patients in stages 2-5 of CKD was lower than that of age and gender pair-matched healthy individuals. Although the cause of reduced REE was unclear, it may be related to decreased food intake and to metabolic disturbances inherent with deterioration of renal function. Further studies will be necessary to clarify this issue.

Topics: Adult; Body Composition; Creatinine; Energy Metabolism; Female; Glomerular Filtration Rate; Homeostasis; Humans; Kidney Diseases; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Models, Biological; Parathyroid Hormone; Reference Values; Rest

To assess the serum level of leptin and its relationship between tumor necrosis factor, and endothelin in patients with chronic renal failure.. Serum level of leptin,tumor necrosis factor and endothelin were measured in 40 patients with chronic renal failure and 20 healthy controls by radioimmunoassay. Correlation analysis was performed between serum level of leptin and tumor necrosis factor and endothelin.. Serum leptin in patients with chronic renal failure was significantly higher than that in healthy control subjects((19.25+/-4.89)microg/L vs. (5.57+/-1.69)microg/L, P<0.01). There was significant positive correlation between serum leptin and tumor necrosis factor and endothelin (r(TNF)=0.829, r(ET)=0.605; both P<0.01).. The abnormal increased serum levels of tumor necrosis factor and endothelin are associated with hyperleptinemia in patients with chronic renal failure.

Topics: Adult; Endothelins; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Tumor Necrosis Factors

Advanced glycation end products (AGEs) and other carbonyl and oxidative stress compounds are supposed to play a critical role in the pathogenesis of several diseases and their complications, i.e., diabetes mellitus, diabetic retinopathy, atherosclerosis, and chronic renal failure. In the present investigation, we were interested in the relationship of AGEs in plasma to other prominent factors in the patients on chronic hemodialysis treatment-27 patients with diabetes mellitus, 35 patients without diabetes mellitus. AGE-group reactivity was estimated using a spectrofluorometric method (excitation 350 nm, emission 430 nm) and is expressed in arbitrary units (AU). We found significantly higher AGEs levels in diabetics than in non-diabetics on regular hemodialysis treatment both before (2.7 +/- 0.7 x 10(4) AU vs. 2.2 +/- 0.6 x 10(4) AU, p < 0.001) and after the dialysis session (2.3 +/- 0.5 x 10(4) AU vs. 1.8 +/- 0.7 x 10(4) AU, p < 0.005). AGEs were significantly reduced during hemodialysis in both groups of patients--by 15.4% in the diabetic go (p < 0.001) and by 17.3% in non-diabetics (p < 0.005). In the patients with diabetes mellitus, AGEs did not correlate with parameters of the glucose metabolism correction (blood glucose, HbA1c). We observed a significant correlation between AGEs and leptin (r = 0.48, p < 0.05) as well as the leptin/body fat ratio (r = 0.56, p < 0.05) only in hemodialyzed patients with diabetes mellitus. These findings suggest more detailed studies to identify the molecular links between carbonyl stress, i.e., advanced glycation end products, and leptin metabolism, sign of microinflammation and hypertension.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Blood Glucose; Body Composition; Cross-Sectional Studies; Diabetes Complications; Diabetes Mellitus; Female; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Skinfold Thickness; Time Factors

Soluble leptin receptor (SLR) is the extracellular part of the leptin receptor. This protein is released into circulation and constitutes the main circulating leptin-binding protein. The aim of our study was to measure SLR concentrations in patients with chronic renal failure (CRF) and healthy subjects and to explore the relationship of SLR to other hormones and cytokines. The patients with CRF had significantly higher serum leptin, TNF-alpha and insulin levels than healthy subjects (25.1+/-23.5 vs. 9.4+/-7.6 ng.ml(-1) (S.D.); 14.2+/-4.2 vs. 4.55+/-2.5 ng.ml(-1); 39.8+/-36.1 vs. 20.3+/-11.1 mU.l(-1)). Serum soluble leptin receptor levels did not differ between these groups (19.1+/-11.3 vs. 19.6+/-6.1 U.ml(-1)). An inverse relationship between serum SLR and leptin levels was found in both groups. In patients with CRF the inverse relationship between SLR and insulin, body fat content and total protein levels were also found, while in healthy subjects only inverse relationship of SLR with insulin and albumin concentrations were detected. We conclude that soluble leptin receptor levels in patients with chronic renal failure do not differ from those of healthy subjects despite higher serum leptin levels in CRF patients. The physiological consequences of this finding require further investigation.

Topics: Blood Proteins; Body Composition; Body Weight; Data Interpretation, Statistical; Humans; Insulin; Kidney Failure, Chronic; Leptin; Receptors, Cell Surface; Receptors, Leptin; Serum Albumin; Skinfold Thickness; Tumor Necrosis Factor-alpha

Topics: Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis; Receptors, Cell Surface; Receptors, Leptin; Tumor Necrosis Factor-alpha

Neuropeptide Y (NPY) is released during sympathetic stimulation and mediates the central effects of the adipostatic hormone leptin. The plasma concentration of NPY and leptin is increased in patients with end stage renal disease (ESRD), but it is unknown whether these substances are related to biochemical markers of sympathetic activity and to alterations in left ventricular (LV) mass and function in these patients.. We investigated the relationship between NPY, norepinephrine (NE), leptin and echocardiographic measurements in a cross-sectional study in 198 patients with ESRD.. NPY was directly related to plasma NE and heart rate but it was largely independent of arterial pressure and of retention of metabolic waste products. NPY was significantly higher in patients with LV hypertrophy and in those with LV systolic dysfunction than in those without these alterations. Of note, NPY emerged as an independent correlate of LV mass index and of LV ejection fraction (LVEF) (both P

Topics: Adult; Aged; Biomarkers; Cohort Studies; Cross-Sectional Studies; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Myocardium; Neuropeptide Y; Norepinephrine; Risk Factors; Ventricular Dysfunction, Left

Resistin is a newly discovered insulin inhibitor secreted by adipocytes. We explored the potential role of resistin in the pathophysiological process of insulin resistance encountered in patients with renal disease.. Resistin blood concentrations, insulin sensitivity index (by intravenous glucose tolerance test), and glomerular filtration rate (GFR; by inulin clearance) were assessed in 30 male patients with immunoglobulin A glomerulonephritis in different stages of renal disease.. Patients with increased resistin blood concentrations had more advanced renal failure and were significantly older. Plasma resistin levels correlated significantly with GFR (r = -0.82; P < 0.0001), plasma homocysteine concentration (r = 0.68; P < 0.001), and age (r = 0.42; P = 0.05), but not with fasted plasma insulin (r = -0.34; P = 0.12), glucose (r = 0.25; P = 0.19), and leptin (r = -0.24; P = 0.21) concentrations; body mass index (r = -0.06; P = 0.75), waist-hip ratio (r = 0.09; P = 0.63), or insulin sensitivity (r = -0.05; P = 0.79). In multiple regression analysis, GFR was the only independent predictor of plasma resistin concentrations in renal patients (r = -0.812; P < 0.0001).. Resistin blood concentrations increase with progressive impairment of renal function. Thus, the kidney seems to be an important site of resistin elimination. However, the greater than 5-fold increase in resistin blood levels apparently is not associated with deterioration in insulin sensitivity in patients with renal disease.

Topics: Adipocytes; Adult; Biomarkers; Blood Glucose; Body Mass Index; Glomerular Filtration Rate; Glomerulonephritis, IGA; Glucose Tolerance Test; Hormones, Ectopic; Humans; Insulin Resistance; Kidney; Kidney Failure, Chronic; Leptin; Lipids; Male; Predictive Value of Tests; Resistin

Experimentally, leptin has a positive effect on bone mass when infused intravenously, but a negative one after intracerebroventricular administration. Renal failure increases its serum level above the concentration beyond which its transport to the brain may be saturated. Thus, we tested, in a chronic haemodialysis population, the hypothesis of a positive relationship between serum leptin and bone mineral density (BMD) when serum levels are above this threshold.. Serum leptin (using a two-site RIA), and BMD at the femoral neck, midshaft, and ultradistal radius, as measured by DEXA, were assessed in 17 female and 16 male chronic dialysis patients, with comparable calcium and phosphate metabolism, age and dialysis duration.. Polynomial regression analysis showed a U-shaped correlation between BMD Z-score, with an inflexion point, which may correspond to the concentration threshold at which leptin blood-brain carrier is saturated. Linear regression analysis showed no correlation between BMD and serum leptin levels below these points but a significant positive correlation between BMD at the two radius sites and leptin levels above these points. The correlation remained significant after adjustment for BMI, serum PTH and duration of dialysis. Leptin levels were twice as high in female patients and associated with higher BMD Z-scores close to zero.. This study suggests a bone-sparing effect of serum leptin in haemodialysis patients only when the serum levels of leptin were higher than the presumed threshold of blood-brain transport saturation. Higher leptin levels in post-menopausal female haemodialysis patients than in male patients may account for their slower bone loss with ageing.

Topics: Aged; Bone Density; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis

Patients with chronic renal failure are characterized by hyperleptinemia, and leptin is presumed to be an anorectogenic hormone. The aim of this prospective study was to analyze changes in body composition and parameters of nutritional status in relation to changes in plasma leptin concentration in uremic patients during the first year of hemodialysis therapy.. 21 patients (10 F, 11 M, mean age 51+/- 3 years, BMI 24.3+/-1.1 kg/m2) were enrolled in this study. Nutritional status was evaluated by anthropometric parameters, estimation of body composition (DEXA method), and biochemical markers (plasma concentrations of albumin, cholesterol, triglycerides, transferrin) and plasma leptin concentration. Tests were performed twice: immediately after initiation of hemodialysis therapy and again 12 months later.. After 12 months of hemodialysis therapy, the changes in body mass (-2.6+/-0.8 kg; p=0.23), total fat mass (TFM) (-0.3+/-0.8 kg; p=0.68) and total lean mass (TLM) (+0.5+/-0.8 kg; p=0.26) were insignificant. Plasma leptin concentration and estimated biochemical nutritional parameters did not change markedly. A significant positive correlation was noticed between TFM and plasma leptin concentration (R=0.521; p=0.02) at the beginning of hemodialysis therapy and between changes in TFM and plasma leptin concentration (R=0.466; p=0.04) after one year.. Plasma leptin concentration does not predict forthcoming changes in body composition and changes of nutritional status in uremic patients after the first year of hemodialysis.

Topics: Body Composition; Body Mass Index; C-Reactive Protein; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Predictive Value of Tests; Renal Dialysis; Statistics as Topic; Uremia

The hormone leptin is considered to have a role in the prevention of osteoporosis and probably acts on bone tissue through inhibition of osteoclasia. Its action has been attributed to interference in osteoprotegerin (OPG)/OPG-ligand equilibrium. Contradictory data also have been reported, casting doubts on the positive effect on bone mass of the hormone, at least in males. To date, the relation between serum leptin levels of dialysis patients and renal osteodystrophy, defined by histomorphometric and histodynamic parameters of bone, has not been studied.. The study included 46 hemodialysis patients (32 men, 14 women; age, 57.2 +/- 11.4 years). A transiliac bone biopsy after double-tetracycline labeling was performed for histological, histomorphometric, and histodynamic studies. Blood samples were drawn for leptin, intact parathyroid hormone (PTH), whole PTH (PTH1-84), OPG, bone alkaline phosphatase, calcium, phosphate, 25-hydroxycholecalciferol, and calcitriol. Serum leptin was measured by means of a radioimmunoassay.. Eighteen patients had mixed osteodystrophy (MO); 17 patients, hyperparathyroidism; 9 patients, adynamic bone disease (ABD); and 2 patients, osteomalacia. Aluminum histochemistry results were positive in 1 patient with ABD and 1 patient with MO. A sex difference was found in serum leptin levels (48.9 +/- 38 ng/mL in women and 12.2 +/- 13.2 ng/mL in men; P < 0.0002). In the entire population, lnleptin correlated significantly with body mass index (BMI; P < 0.01). SD score (SDS) leptin (adjusted for BMI, sex, and age) correlated inversely with PTH1-84 level and osteoclastic surface (OcS/BS; P < 0.05) and had a borderline correlation with bone formation rate. Correlations between leptin levels and other parameters were enhanced in men. SDS leptin correlated inversely with OcS/BS (P < 0.01), osteoclastic number (P < 0.01), and mineral apposition rate (P < 0.01). In addition, SDS leptin had a borderline inverse correlation with osteoblast surface (P < 0.06) and significant correlation with OPG level (P < 0.05). No difference was found in serum leptin levels between histological groups.. The reported data confirm the finding of a positive relation between serum leptin level and BMI and greater levels in women compared with men. Serum leptin level is connected to bone resorption and also bone formation, both inversely related to serum leptin levels. The decrease in osteoclasia that accompanies increasing serum leptin levels does not seem to be related to an enhanced OPG effect because it was accompanied by decreased OPG levels. Low-turnover bone disease does not appear to be caused by increased serum leptin levels. The nature of the interrelation between serum leptin and PTH1-84 levels requires further study.

Topics: Aged; Biomarkers; Body Mass Index; Chronic Kidney Disease-Mineral and Bone Disorder; Female; Glycoproteins; Humans; Hyperthyroidism; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Osteomalacia; Osteoprotegerin; Parathyroid Hormone; Receptors, Cytoplasmic and Nuclear; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Renal Dialysis; Sex Factors; Statistics as Topic

Malnutrition is prevalent in patients with end-stage renal disease (ESRD). Elevated serum leptin levels were thought to contribute to the anorexia and poor nutrition in renal failure. However, studies of the relationship between nutritional status and leptin concentration in chronic renal failure have yielded conflicting results. Plasma insulin-like growth factor I (IGF-I) level has been used as an indicator of nutritional status in patients with renal failure. The relationship between leptin and IGF-I is controversial. The present study was conducted with the aim of assessing the relationship between nutritional status, hyperleptinemia, and serum IGF-I. Seventeen ESRD patients (8 male, 9 female), aged 8-18 years (mean 15.3+/-3.3 years) and undergoing standard hemodialysis for 58.8+/-23.1 months were enrolled. Nine age-matched healthy children served as controls. In all patients, energy and protein intakes were 40-70 kcal/kg per day and 1-1.54 g/kg per day, respectively. Predialysis serum leptin and IGF-I levels were measured by radioimmunoassay. Body mass index was decreased in 13 (76%) patients. Triceps skinfold thickness (TST) was reduced (below the 5th percentile) in 7 (41%), whereas mid arm circumference and mid arm muscle circumference were reduced in 14 (82.5%) and 13 (76.5%), respectively. The median serum leptin level was significantly higher in patients than in controls [13.7 interquartile range (IQR) 30.50 pg/ml vs. 6.50 IQR 8.65 pg/ml, P=0.01]. The median serum IGF-I level was lower in the patients (205.1 ng/ml IQR 194.4 ng/l) than controls (418.0 ng/l IQR 310.5 ng/ml) ( P=0.01). IGF-I levels were more decreased in patients with severe malnutrition, defined according to TST (145.0 ng/ml IQR 125.5 ng/l) than patients without malnutrition (301.2 ng/l IQR 218.8 ng/ml) ( P=0.03) and healthy children ( P=0.002). Although statistically not significant, IGF-I levels tended to be decreased, while leptin levels were increased. The median plasma insulin concentration was 15 microU/ml (1.63-45.80) and did not correlate with leptin and IGF-I levels. In conclusion, the results of this study confirm the presence of high circulating plasma leptin levels, which may be one of the many factors involved in the pathogenesis of the malnutrition in children on hemodialysis.

Topics: Adolescent; Anthropometry; Arm; Biomarkers; Blood Urea Nitrogen; Body Mass Index; Body Weight; Child; Creatinine; Female; Humans; Insulin; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Nutritional Status; Protein-Energy Malnutrition; Renal Dialysis; Skinfold Thickness

(1) To evaluate the impact of body composition and gender on serum leptin concentration in hemodialysis patients. (2) To study which marker of adiposity is most appropriate in Taiwanese hemodialysis patients without diabetes. (3) To compare the nutrition status between nonlean and lean subjects.. Serum leptin concentrations were measured by radioimmunoassay collected in 88 hemodialysis patients without diabetes. Bioimpedance analysis was performed to determine percent fat mass (%FM), lean body mass (LM), and total body water (TBW). Body mass index (BMI) was calculated as weight/height2. Albumin and transferrin were measured by standard laboratory methods.. Serum leptin levels were more correlated with percent fat mass (r = 0.697; P < 0.001) than with body fat mass (r = 0.672; P < 0.001) or with BMI (r = 0.594; P < 0.001) in the group as a whole and in each subgroup when analyzed separately by gender. The mean (+/- SD) serum leptin levels were 32.5 +/- 34.3 ng mL(-1) in women subjects and 13.6 +/- 15.5 ng mL(-1) in men subjects (P < 0.001). Multiple regression analysis in all subjects revealed that serum leptin levels were independently affected by percent fat mass and gender. Adiposity corrected serum leptin, such as leptin/BMI, leptin/percent fat mass, and leptin/body fat mass was significantly different between sexes (P < 0.001). The significantly higher serum leptin concentrations in women than in men were observed in obese subjects with BMI > 25 kg/m2 (P < 0.001) as well as nonobese subjects with BMI < 25 kg/m2 (P < 0.05). There were no differences in lean mass and albumin between nonlean and lean subjects.. Gender and adiposity had impact on serum leptin levels in hemodialysis patients without diabetes. In terms of adiposity, serum leptin levels had stronger correlation with percent fat mass than with body fat mass (FM) or BMI in Taiwanese hemodialysis patients. Steady-state serum leptin levels could serve as valuable clinical markers for the body adiposity in stable hemodialysis patients without diabetes. Protein malnutrition markers and lean mass should be checked in lean subjects for the evaluation of the protein stores of hemodialysis patients.

Topics: Adult; Aged; Biomarkers; Body Composition; Body Mass Index; Case-Control Studies; Cohort Studies; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Probability; Radioimmunoassay; Reference Values; Renal Dialysis; Risk Assessment; Severity of Illness Index; Sex Factors; Taiwan; Treatment Outcome

Serum leptin decreases during growth hormone (hGH) treatment and pre-treatment values have been suggested as a predictor of the response to hGH in GH deficiency (GHD) but not in non-GHD syndromes. To investigate whether this holds true in children with chronic renal failure (CRF), we evaluated changes in serum leptin, insulin-like growth factor-I (IGF-I) and height before(b) and during the 1st year (3 months, 6 months, 9 months, 12 months) of hGH treatment (1 IU/kg per week) in 11 children (median age(b) 10.1 years, mean height(b) -2.9 SDS) with CRF. Serum leptin and IGF-I were compared with values from healthy children. Each patient also served as his/her own control, with values during treatment compared with those before treatment. Growth improved in all patients during treatment (mean change(12 m) +7.2 cm, change in height SDS(12 m) +0.5, P=0.001). Weight decreased (median decrease(12 m) 0.3 SDS, P=0.02) but body mass index (BMI) and serum leptin did not change during treatment. Serum IGF-I levels were low before (mean -1.1 SDS) but increased during hGH treatment, the increment being greatest at 10 days (mean increment +1.9 SDS, P<0.0001). Serum leptin(b) did not correlate with change in serum IGF-I(10d), height(12 m) or weight(12 m). Serum IGF-I SDS(b) correlated with height SDS at 12 months ( r=0.80, P=0.006) of hGH treatment. Serum leptin(b) correlated with BMI ( r(s)=0.75, P=0.01). Levels adjusted for BMI did not differ from values in healthy children and did not change during treatment. Despite an IGF-I and growth response during hGH treatment, serum leptin did not change and pre-treatment values did not predict the growth response in these children with CRF.

Topics: Adipose Tissue; Adolescent; Biomarkers; Body Height; Body Mass Index; Body Weight; Child; Child, Preschool; Female; Growth Hormone; Human Growth Hormone; Humans; Infant; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Radioimmunoassay

Hyperleptinemia is also common in chronic renal failure, particularly in CAPD. On the other hand, cardiovascular events related to thrombosis are a predominant cause of death and account also for an important morbidity in uremic patients. Treatment with recombinant human erythropoietin (rHuEPO) may shift the precarious hemostatic balance towards thrombosis. Therefore, the aim of the study was to assess the relationships between leptin and platelet aggregation and some hemostatic parameters in CAPD patients treated with rHuEPO. The study was performed on 15 patients maintained on CAPD given rHuEPO and 13 subjects without rHuEPO therapy served as a control group. Platelet aggregation was studied in both platelet-rich plasma (PRP) and in the whole blood. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) (antigens and activities), von Willebrand factor, trombomodulin, protein C, thrombin activatable fibrinolysis inhibitor (TAFI) and leptin (serum and dialysate) were assayed by using commercially available kits. Patients in both groups studied did not differ significantly with respect to age, BMI, duration of renal replacement therapy, and other hematological and hemostatic parameters studied as well as leptin serum and dialysate leptin. In CAPD patients treated with rHuEPO serum and dialysate leptin significantly correlated with tissue factor pathway inhibitor, protein C, thrombomodulin, ristocetin-induced platelet aggregation in the whole blood and PRP. In CAPD patients not treated with rHuEPO the significant correlations were observed between serum and dialysate leptin and protein C. Positive correlations between platelet aggregation and leptinemia in CAPD patients might indicate that hyperleptinemia could be associated with the cardiovascular disease in dialyzed patients. Leptin might contribute at least in part to the thrombotic complications observed in CAPD patients.

Topics: Adult; Anemia; Erythropoietin; Female; Hemostasis; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Platelet Aggregation; Recombinant Proteins

Elevated serum leptin (S-leptin) levels have been reported in patients with end-stage renal disease (ESRD). Apart from the decreased glomerular filtration rate (GFR), body composition and inflammation may affect leptin levels in ESRD. Leptin circulates both free of and bound to soluble leptin receptors (sOB-R), which are the main determinants of leptin activity and have not been described in ESRD until now.. To analyze the association between S-leptin, sOB-R, and inflammation and body composition, we studied 149 (62% males) normal weight (BMI 24.7 +/- 0.4 kg m(-2)) ESRD patients (51 +/- 1 years old) shortly before the start of dialysis (GFR 7.0 +/- 0.2 mL min(-1)). sOB-R and plasma interleukin-6 (IL-6; n= 113) levels were evaluated using ELISA, S-leptin using RIA, and body composition was assessed by X-ray absorptiometry (n = 139). Forty-one healthy subjects age (51 +/- 1 years), BMI (23.6 +/- 0.5 kg m(-2)) and gender-matched (59% males) were used as controls.. Median S-leptin was higher in the ESRD patients (10.0 ng mL(-1)) compared with the controls (3.9 ng mL(-1)) (P < 0.001). The median sOB-R did not differ significantly between the ESRD patients (44 U mL-1) and the controls (37 U mL-1). Thus, the sOB-R/S-leptin ratio was lower in the ESRD patients (9.5 +/- 1.2 vs. 12.3 +/- 1.8; P < 0.01) than the controls. A negative correlation was observed between S-leptin and sOB-R (Rho = -0.42; P < 0.0001) in the ESRD patients, a positive correlation was observed between lean body mass and the sOB-R/S-leptin ratio (Rho = 0.33, P = 0.0001) whereas fat mass was negatively correlated to both sOB-R (Rho = -0.26, P = 0.002), and the sOB-R/S-leptin ratio (Rho = -0.62, P < 0.0001). Positive correlations were observed between IL-6 and S-leptin (Rho = 0.19; P < 0.05) and weak but significant body fat mass (Rho = 0.20; P < 0.05), respectively.. This study demonstrates that despite markedly elevated S-leptin levels in the ESRD patients, sOB-R did not differ from the controls. In view of the anorexigenic and pro-atherogenic effects of leptin, further elucidation of the consequences of free bioactive leptin in the development of complications such as malnutrition and cardiovascular disease in ESRD patients is required.

Topics: Body Composition; Case-Control Studies; Diabetes Mellitus; Female; Humans; Interleukin-6; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Prospective Studies; Receptors, Cell Surface; Receptors, Leptin; Statistics, Nonparametric

In vitro and in vivo data suggest that markers of inflammation and nutritional status may be risk factors for the progression of chronic kidney disease.. We investigated whether higher levels of C-reactive protein (CRP) and leptin were risk factors for progression of chronic kidney disease in the Modification of Diet in Renal Disease (MDRD) Study. Frozen samples were assayed for high sensitivity C-reactive protein (CRP) or leptin in 804 patients. CRP and leptin were then evaluated as risk factors for glomerular filtration rate (GFR) decline using univariate and multivariable analyses.. At baseline, the mean (median) CRP in Study A (GFR between 25 and 55 mL/min/1.73 m2) and Study B (GFR between 13 and 24 mL/min/1.73 m2) were 0.48 (0.25) and 0.46 (0.20) mg/dL, respectively, while the mean (median) leptin in Study A and Study B were 15.2 (9.80) and 15.1 (7.80) ng/mL, respectively. Mean follow-up time was 2.2 years. The mean GFR decline was -4.33 and -3.65 mL/min/year in Study A and B, respectively. There was no significant association between the rate of GFR decline with the level of CRP or leptin in multivariable analysis in Study A [0.08 (-0.14, 0.30) mL/min/year slower GFR decline per twofold increase in CRP level; and 0.14 (-0.13, 0.40) mL/min/year slower GFR decline per twofold increase in leptin level], or in multivariable analysis in Study B [-0.05 (-0.28, 0.18) mL/min/year faster GFR decline per twofold increase in CRP level; and -0.12 (-0.42, 0.19) mL/min/year faster GFR decline per twofold increase in leptin level].. Higher serum levels of CRP and leptin are not independent risk factors for progression of non-diabetic kidney disease.

Topics: Adolescent; Adult; Aged; C-Reactive Protein; Cohort Studies; Diet; Disease Progression; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutrition Assessment; Predictive Value of Tests; Regression Analysis; Risk Factors

Females are characterized by significantly higher plasma leptin concentration than males. It seems likely that sex hormones influence leptinemia independently from differences in body composition. The aim of the present study was to analyze the contribution of plasma concentrations of testosterone and estradiol on leptinemia in hemodialyzed patients.. 110 hemodialyzed patients--HD (60 M, 50 F) and 70 healthy subjects (HS) (30 M, 40 F) were enrolled in this study. Plasma leptin, testosterone or estradiol and CRP concentrations and body composition by dual-energy X-ray absorptiometry (DEXA) were assessed.. Total body fat was significantly higher in females than in males (27.5 +/- 1.5% vs. 17.2 +/- 1.0% of body weight in HD and 36.0 +/- 1.0% vs. 18.2 +/- 1.4% in HS, respectively). Plasma leptin concentrations were markedly higher in females than in males both in HD (27.9 +/- 5.4 ng/ml vs. 9.6 +/- 1.9 ng/ml) and HS (16.5 +/- 1.7 ng/ml vs.3.1 +/- 0.4 ng/ml). A highly significant, strong positive correlation was found between total fat mass (TFM) and leptinemia in all studied groups. No significant univaried correlation between plasma leptin and testosterone or estradiol concentrations respectively was found both in HD and HS. Multiple regression analyses showed that the main determinant of leptinemia is TFM (beta = 0.623 and 0.798 in HS females and males respectively, and beta = 1.058 and 0.797 in HD females and males respectively). Plasma concentration of testosterone (beta = -0.139 and beta = -0.075 in male HD and HS respectively) and estradiol (beta = 0.199 and beta = 0.046 in females HD and HS, respectively) contributed to leptinemia only in a minor degree.. Both testosterone and estradiol are minor contributors to leptinemia both in HS and HD patients. The main determinant of leptinemia in these subjects is total body fat mass.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Body Composition; Enzyme-Linked Immunosorbent Assay; Estradiol; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Regression Analysis; Renal Dialysis; Testosterone

To date, peritoneal dialysis has been performed almost exclusively using dialysis solutions containing glucose as the osmotic agent. Use of these solutions is fraught with problems regarding adequate fluid removal from the body and is also associated with undesirable metabolic effects; hence the search for alternative osmotic agents. A dialysis solution with the glucose polymer icodextrin generates ultrafiltration on the principle of colloidal osmosis. The aim of the study was to establish the effect of icodextrin-base dialysis solution on the magnitude of ultrafiltration and evaluate selected metabolic parameters of patients treated by ambulatory peritoneal dialysis.. A total of 9 patients whose glucose-based solution was replaced by an icodextrin-based solution during the night-time exchange were evaluated. A control group of 9 patients used glucose-solution during all exchanges. Night-time bag ultrafiltration, blood pressure, and the serum levels of lipids, insulin, leptin, maltose, and amylase were determined before icodextrin administration (time 0), at one-month intervals (time 1, 2, 3), and one month after study completion (time 4). In icodextrin-treated patients, ultrafiltration rose from 246.5 +/- 60.5 ml (mean +/- SEM) at time 0 to 593.1 +/- 87.4 ml; p < 0.01, at time 1, to 547 +/- 67 ml; p < 0.05, at time 2, and to 586.7 +/- 58.8 ml; p < 0.01, at time 3, the icodextrin administration led to a rise in maltose from 0.02 +/- 0.01 g/l at time 0 to 0.1 +/- 0.1 g/l; p < 0.01, at time 1, to 1.0 +/- 0.09 g/l; p < 0.01, at time 2, and to 1.1 +/- 0.09 g/l; p < 0.01, at time 3, with a fall to zero values at time 4 (NS). Icodextrin administration was followed by a decrease in leptinemia from 34.6 +/- 17.2 ng/ml at time 0 to 21.7 +/- 8.9 ng/ml; p < 0.05, at time 1, to 21.4 +/- 9.5 ng/ml; p < 0.05, at time 2, and to 15.9 +/- 24.1 ng/ml; p < 0.05 at time 4. Insulin and lipid levels were not affected. There was no change in the above parameters in the control group. Icodextrin-treated patients reduced their antihypertensive medication, but not statistically significantly.. Icodextrin administration significantly increase ultrafiltration thus providing for effective control of hydration status without the need for high-level glucose-based dialysis solutions. The use of a glucose polymer-based dialysis solution is associated with a significant yet reversible rise in serum maltose. The decrease in leptin may signal a reduction in body weight after replacing glucose in dialysis solutions with icodextrin, or enhanced rates of leptin elimination as a result of ultrafiltration-induced convective transport.

Topics: Adult; Aged; Blood Pressure; Dialysis Solutions; Female; Glucans; Glucose; Humans; Icodextrin; Kidney Failure, Chronic; Leptin; Lipids; Male; Maltose; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Ultrafiltration

Recombinant human erythropoietin (rHuEPO) is used to correct anemia in the majority of hemodialysis patients, but a few patients can maintain greater hematocrits without the use of rHuEPO. We aim to investigate which factors stimulate erythropoiesis, other than rHuEPO, in hemodialysis patients. One hundred fifty-eight patients undergoing regular hemodialysis treatment participated in a cross-sectional study. To keep the target hematocrit of 30%, 133 patients (84%) were administered rHuEPO, but 25 patients (16%) did not need rHuEPO. Mean hematocrits were 33.4% +/- 4.6% in patients who did not need rHuEPO and 30.9% +/- 4.0% in those administered rHuEPO. In the analysis of factors contributing to the lack of requirement of rHuEPO with multivariate logistic regression analysis, years on dialysis therapy and body mass index (BMI) were determined to be independent factors with odds ratios of 1.12 (95% confidence interval [CI], 1.02 to 1.23; P = 0.02) and 1.36 (95% CI, 1.13 to 1.63; P = 0.001), respectively. Neither serum erythropoietin level, albumin concentration, nor normalized protein catabolic rate contributed to the lack of requirement of rHuEPO. BMI correlated closely with log serum leptin level (r = 0.55; P < 0.0001), and log serum leptin level correlated inversely with rHuEPO dose (r = -0.18; P = 0.03). These results indicate that 16% of hemodialysis patients could maintain greater hematocrits without the administration of rHuEPO, and independently contributing factors were greater BMI and more years on hemodialysis therapy. Regarding nutritional parameters, a relatively greater BMI, possibly through effects of greater leptin levels, may stimulate erythropoiesis in uremic patients even in the absence of sufficient erythropoietin production.

Topics: Body Mass Index; Cross-Sectional Studies; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Multivariate Analysis; Recombinant Proteins; Regression Analysis; Renal Dialysis

Anorexia and weight loss frequently accompany chronic renal failure (CRF). Although multiple metabolic changes occur during CRF, a bulk of evidence indicates that the decrease in caloric intake plays a major role in CRF-induced weight loss. Recently, it has been suggested that elevated plasma leptin concentrations could contribute to anorexia and to downregulation of leptin gene expression in CRF patients. However, in some CRF patients, plasma leptin concentrations have been found to be lower than one could expect. Thus we assumed that inhibition of leptin synthesis plays an important role in the regulation of plasma leptin concentrations in CRF patients.. To test this assumption, the leptin mRNA level in rat white adipose tissue from ad-libitum-fed control (sham operated), pair-fed control (sham operated) and rats with experimentally induced CRF has been measured by Northern blotting analysis. In addition, serum leptin concentration (by radioimmunoassay) was determined in all three groups of animals.. The results of the present study indicate that in experimental CRF the leptin mRNA level is decreased by about 50% as compared to the sham-operated animals (ad-libitum-fed and pair-fed controls). The mean serum leptin concentration in CRF rats was essentially similar to the leptin concentration in sham-operated ones.. The data obtained suggest that in CRF animals the serum leptin concentration might be affected not only by the decrease in leptin removal in the kidney, but also by the decrease in leptin secretion from adipose tissue. Furthermore, the results of the study suggest that leptin may be only one of many factors involved in the pathogenesis of malnutrition associated with CRF.

Topics: Adipose Tissue; Animals; Kidney Failure, Chronic; Leptin; Male; Nephrectomy; Osmolar Concentration; Postoperative Period; Rats; Rats, Wistar; Reference Values; RNA, Messenger

Patients with chronic renal failure are frequently characterized by malnutrition, hyperleptinaemia and metabolic acidosis. Both hyperleptinaemia and chronic metabolic acidosis are presumed to contribute to the pathogenesis of malnutrition observed in this group of patients. It has been reported, that in vitro adipocytes exposed to acidotic medium decrease leptin secretion. The aim of present study was to analyze the possible impact of uraemic metabolic acidosis on leptinaemia in haemodialysis patients with chronic renal failure. - 94 haemodialysed patients (58 M, 36 F; mean age 45 +/- 1 years) were enrolled in this study. 56 patients were on haemodialysis treatment for one year using an acetate dialysis fluid, while 38 patients were haemodialysed at least for 3 months with a dialysate buffered with bicarbonate. Plasma leptin concentration, blood gases and body composition were assessed in all examined subjects. - Patients haemodialysed with an acetate and bicarbonate buffered dialysate did not differ with respect to body weight, body mass index (BMI), total fat mass (TFM) and plasma leptin concentration. Patients haemodialysed with an acetate buffered dialysate were characterized by a significantly more severe metabolic acidosis than patients on bicarbonate haemodialysis. Patients were divided according to the actual hydrogen ion concentration: over 60 nmol/l, 45-60 nmol/l and below 45 nmol/l. These subgroups did not differ significantly by body weight, BMI and TFM. Only a slightly (not significantly), lower median leptinaemia was found in patients with elevated hydrogen ion concentration. No significant correlation was noticed between blood hydrogen or hydrocarbonate ion concentration respectively and logarithmic values of plasma leptin concentration (tau = 0.025, p = 0.72; tau = - 0.021, p = 0.76 respectively). - From results obtained in this study we may conclude that, blood hydrogen ion concentration does not influence substantially or only moderately to plasma leptin concentration in haemodialysed patients.

Topics: Acidosis; Bicarbonates; Body Composition; Female; Humans; Hydrogen-Ion Concentration; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Renal Dialysis; Statistics, Nonparametric

Topics: Adult; Body Mass Index; Child; Humans; Kidney Failure, Chronic; Leptin; Obesity

To examine the relationship between serum leptin levels (SLL) and metabolic acidosis in patients with chronic renal failure (CRF).. SLL in control patients and in predialysis patients with CRF were measured and compared. SLL before and after correction of acidosis in patients with CRF were also compared.. Twenty-five patients with CRF (10 men and 15 women) aged 51.2 +/- 10.4 years and control patients (healthy subjects, 23 men and 25 women) aged 42.1 +/- 12.6 years were studied.. Five percent sodium bicarbonate (NaHCO(3), 2 to 3 mL/kg) was intravenously infused on the morning of the first day of treatment. NaHCO(3) was taken orally at a dosage of 50 to 200 mg/kg/d for 3 to 5 days thereafter.. SLL before and after NaHCO(3) treatment was measured by radioimmunoassay, and blood gas was measured before and after correction of metabolic acidosis in patients with CRF.. SLL in the normal control group (n = 48) was 10.04 +/- 7.0 ng/mL and was realated to body mass index (BMI) (P =.0331). SLL in men (n = 23) was lower than that in female controls (n = 25, P <.01). SLL in patients with CRF (n = 25) before (plasma HCO(3)(-), 13.03 +/- 3.05 mmol/L) and immediately after improvement of metabolic acidosis (plasma HCO(3)(-), 18.35 +/- 4.21 mmol/L) was 14.52 +/- 9.27 ng/mL and 15.34 +/- 11.89 ng/mL (P >.05), respectively. SLL measured 3 to 5 days after treatment for metabolic acidosis (plasma HCO(3)(-), 20.46 +/- 4.03 mmol/L) was 19.33 +/- 14.58 ng/mL, which was significantly higher than that in the normal control group and that in acidotic patients before NaHCO(3) treatment (P <.01).. SLL in acidotic patients with CRF were comparable to that in control subjects, and SLL was significantly increased after correction of metabolic acidosis in patients with CRF. The preliminary results suggest that hyperleptinemia in patients with CRF may be masked by metabolic acidosis and that metabolic acidosis may inhibit leptin synthesis or secretion. Further studies are needed to clarify the mechanisms.

Topics: Acidosis; Administration, Oral; Adult; Aged; Blood Gas Analysis; Body Mass Index; Case-Control Studies; Female; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Radioimmunoassay; Sex Factors; Sodium Bicarbonate

Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions.. We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session.. Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes. The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected.. Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.

Topics: Body Mass Index; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutritional Status; Protein Binding; Reference Values; Renal Dialysis

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. Markedly elevated leptin levels have been documented in uremic patients, especially in those who are treated by peritoneal dialysis (PD). However, the role of hyperleptinemia in uremic patients is not clear, and it is not known whether elevated leptin levels contribute to uremic anorexia and changes in body composition. In this prospective study, serum leptin, C-reactive protein (CRP), plasma insulin, and body composition (dual-energy x-ray absorptiometry) were measured in 36 patients (53 +/- 1 yr) close to start and after about 1 yr of PD. In addition, markers of dialysis adequacy and urea kinetics were followed during treatment with PD. During PD, the total body fat mass (20.5 +/- 1.0 to 22.9 +/- 1.3 kg; P < 0.01), truncal fat mass (11.5 +/- 0.7 to 13. 2 +/- 0.9 kg; P < 0.001), and serum leptin levels (20.1 +/- 3.8 to 35.6 +/- 6.8 ng/ml; P < 0.01) increased markedly, especially in patients with diabetes mellitus. Twenty-five PD patients that lost lean body mass during PD had significantly (P < 0.05) elevated initial CRP levels (14 +/- 2 mg/L) compared to 11 patients (<10 mg/L) who gained lean body mass during PD. A significant increase in serum leptin levels (20.9 +/- 4.2 to 42.7 +/- 4.0 ng/ml; P < 0.001) was observed in those patients who lost lean body mass, whereas no such change (18.4 +/- 8.4 to 19.2 +/- 6.4 ng/ml) was observed in the patients that gained lean body mass during PD treatment. The present longitudinal results demonstrate that serum leptin level and body fat content increase markedly during PD, especially in diabetic patients. Patients that lost lean body mass during PD had higher initial CRP levels and increased their serum leptin levels significantly during PD compared to those patients that gained lean body mass. Additional studies are therefore needed to elucidate the role of hyperleptinemia and inflammation in causing anorexia, protein-malnutrition, and changes in body composition during treatment with PD.

Topics: Absorptiometry, Photon; Body Composition; C-Reactive Protein; Diabetic Nephropathies; Female; Glomerulonephritis; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nephritis; Peritoneal Dialysis; Prospective Studies

Leptin is a protein hormone produced predominantly by adipocytes that affects food intake and energy expenditure. Its serum levels are significantly higher in patients with chronic renal failure compared to healthy subjects. The aim of this study was to compare serum leptin levels in hemodialyzed patients with type II diabetes mellitus (n=26) with body content-matched hemodialyzed patients without diabetes (n=26) and to explore the relationship between parameters of the long term diabetes metabolic control and serum leptin levels. Serum leptin levels in diabetic patients did not significantly differ from those of non-diabetic patients (25.3+/-8.8 vs 25.7+/-8.7 ng/ml). Serum leptin levels in diabetic patients positively correlated with body fat content, body mass index and predialysis serum insulin levels. No significant relationship were observed between serum leptin levels and blood glucose, glycated hemoglobin, glycated protein, serum urea, creatinine, leukocyte count and total hemoglobin respectively. The multiple stepwise regression analysis revealed that body fat content together with body mass index accounted for 77.8% of variations in predialysis serum leptin levels, while insulin levels and the parameters of diabetes metabolic control had only slight prediction value for leptin concentrations. We conclude that serum leptin levels in hemodialysed patients with type III diabetes mellitus do not significantly differ from those of hemodialysed non-diabetic patients. The body fat content and body mass index are the strongest predictors of serum leptin levels, while parameters of long term diabetes metabolic control play probably only minor direct role in its regulation.

Topics: Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Reference Values; Regression Analysis; Renal Dialysis; Urea

Chronic renal failure (CRF) is often accompanied by hyperleptinemia caused by deficient renal metabolism of leptin and possibly increased leptin production, which in turn may result from the hyperinsulinemia and increased proinflammatory cytokine levels in patients with CRF. The hyperinsulinemia and insulin resistance observed in patients with CRF improve on supplemented very low protein diets (SVLPDs). The goal of our study is to determine whether the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is accompanied by improvement in hyperleptinemia. Thirteen patients were studied before and 1 year after following SVLPDs providing 0.3 g/kg/d of protein, supplemented with amino acids and ketoanalogues. After 1 year, patients showed markedly less hyperinsulinemia (7.4 +/- 1.6 versus 13.8 +/- 2 microU/mL at the start of diet; P: = 0.05) and insulin resistance, whereas serum leptin levels remained unchanged (16.1 +/- 4.7 versus 19.1 +/- 7.4 ng/mL at start of the study; P: = not significant). The initial correlation between serum leptin level and percentage of body fat persisted during follow-up. No correlation was found between insulin and leptin levels or between the variation of these two parameters during the study. Our study shows that the correction of hyperinsulinemia and insulin resistance in patients with CRF by SVLPDs is not accompanied by improvement in hyperleptinemia, which consequently does not appear to result from changes in carbohydrate metabolism.

Topics: Dietary Proteins; Humans; Insulin; Kidney Failure, Chronic; Leptin

Serum leptin levels are increased in chronic renal failure (CRF) and may potentially contribute to protein malnutrition in this disorder.. Following a cross-sectional design, we performed a nutritional survey in a wide sample of uremic patients treated conservatively (n = 87), with peritoneal dialysis (n = 71) and with hemodialysis (n = 53). Then, we analyzed the correlation between serum leptin levels and markers of protein malnutrition. We used a multivariate approach, taking into consideration the confounding effect of other factors on the correlation between hyperleptinemia and protein malnutrition.. Both univariate and multivariate analysis disclosed a poor correlation between hyperleptinemia and markers of protein malnutrition. In fact, there were trends to a positive correlation between leptinemia and body protein stores, as estimated from the scrutinized markers. Persistence of the basic correlation between general intake, fat mass and leptin in CRF could partially explain these findings, but neither a negative correlation between leptin levels nor protein nutritional state could be disclosed after controlling for this factor.. Our results do not support a first-line role for hyperleptinemia in the genesis of protein malnutrition of uremia.

Topics: Adult; Aged; Biomarkers; Body Mass Index; Female; Humans; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Multivariate Analysis; Peritoneal Dialysis, Continuous Ambulatory; Prealbumin; Protein-Energy Malnutrition; Renal Dialysis; Serum Albumin; Transferrin; Uremia

This was the first Korean-Polish seminar on renal replacement therapies which provided a survey of current research being carried out in both countries, delivered by leading experts in this field. The topics included malnutrition in uremia, biocompatibility, risk factors and complications in renal replacement therapy, diabetic nephropathy, new solutions for peritoneal dialysis, and peritoneal transport. The organizers strove to select the topics which are currently of interest to researchers from both countries with the purpose to compare results and stimulate discussion concerning possible collaboration in the future.

Topics: Cardiovascular Diseases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Leptin; Nutrition Disorders; Peritoneal Dialysis, Continuous Ambulatory; Risk Factors; Uremia

This paper is a summary of results obtained in our studies on leptinemia in patients with chronic renal failure treated with recombinant human erythropoietin (rHuEPO), in kidney transplant patients, in patients with essential hypertension, and in pregnant women with preeclampsia. In this study, we found that rHuEPO treatment has a suppressive effect on leptinemia in patients with endstage renal failure. These results suggest that the appetite stimulating effect of rHuEPO may be mediated by a reduction of leptin synthesis and release. At the early stage of successful kidney transplantation, a significant decline of leptinemia was noticed, which was not related either to the excretory function of the graft or the kind and dose of immunosuppressants. In kidney transplant patients with grafts functioning well for 2.5 years, significantly elevated leptinemia was found. From these results, we may conclude that factors other than the excretory function of the graft and the kind and dosage of immunosuppressants may be involved in the pathogenesis of abnormal leptinemia in these patients. Both in normotensive subjects and patients with essential hypertension, a positive correlation was found between leptinemia and mean blood pressure, suggesting that leptin may be involved in the regulation of blood pressure. Both healthy and preeclamptic pregnant women show higher leptinemia than nonpregnant women. In preeclamptic women, leptin levels in maternal vein blood, umbilical cord blood, and amniotic fluid were significantly higher than respective values found in healthy pregnant women. In contrast to healthy pregnant and nonpregnant women, in women with preeclampsia, no correlation was found between the body mass index (BMI) and leptinemia. In preeclamptic women the abnormally elevated leptinemia was not related to blood pressure. Finally, no correlation was found between leptinemia in maternal and umbilical cord blood. From these studies, it follows that the elucidation of abnormal leptin secretion in the pathogenesis of preeclampsia needs further study.

Topics: Adipose Tissue; Amniotic Fluid; Appetite; Blood Pressure; Blood Proteins; Body Mass Index; Erythropoietin; Female; Fetal Blood; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Pre-Eclampsia; Pregnancy; Proteins

Circulating leptin, which is partly cleared by the kidney, has been reported to increase with chronic renal failure and thus may play a role in the weight loss of patients with chronic renal failure. We investigated the association of body weight loss with the serum leptin concentration in Japanese hemodialysis patients. The relationship between serum leptin and the body mass index (BMI) or body fat mass was compared among 181 patients undergoing hemodialysis and 185 control subjects. There was no difference in the serum leptin concentration between the hemodialysis patients (HD) and controls (C) for either the men (3.9 +/- 0.2 ng/mL for HD, n=117; 3.9 +/- 0.3 ng/mL for C, n=89; NS) or women (8.9 +/- 1.2 ng/mL for HD, n=64; 7.4 +/- 0.5 ng/mL for C, n=96; NS), whereas BMI of the hemodialysis patients was significantly lower than that of the controls for both the men (20.1 +/- 0.2 kg/m2 for HD, 22.4 +/- 0.3 kg/m2 for C, P < 0.001) and women (19.2 +/- 0.3 kg/m2 for HD, 22.0 +/- 0.4 kg/m2 for C, P < 0.001). The serum leptin/body fat mass ratio was significantly correlated with the weight change of the patients during a follow-up evaluation period of 17 months (r = -0.37, P < 0.05 for men, n=27 and r = -0.53, P < 0.005 for women, n=28), indicating the possibility that a relatively high level of serum leptin had induced weight loss in the hemodialysis patients. The serum leptin/body fat mass ratio also showed a significant inverse correlation with the duration of hemodialysis (r = -0.31, P < 0.05 for men and r = -0.49, P < 0.05 for women). A multiple regression analysis indicated that the body fat mass was significantly correlated with serum leptin concentration, whereas the fat distribution did not have any relationship with leptin. These data indicate that a high level of serum leptin relative to the body fat mass might be associated with weight loss in long-term hemodialysis patients. The serum leptin level relative to the body fat mass also seems to have been affected by the duration of hemodialysis.

Topics: Adipose Tissue; Body Mass Index; Case-Control Studies; Female; Humans; Japan; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Regression Analysis; Renal Dialysis; Weight Loss

Leptin and neuropeptide Y (NPY) seem to play an important role in food intake and energy expenditure. Leptin is secreted by adipose tissue in proportion fo fat stores and is presumed to be an important anorectic hormone. NPY is produced by the hypothalamus, and in contrast to leptin, is one of the most potent appetite stimulants yet demonstrated. On the other hand, in most patients increased appetite is present after successful kidney transplantation. Finally, a stimulatory effect of glucocorticoids on leptin secretion was reported. The present study aimed to assess the relationship between plasma leptin and NPY levels and body mass index (BMI) in haemodialyzed patients (HDP) with chronic renal failure and in kidney transplant patients (KTP). In both groups, BMI was of the same magnitude as in healthy controls. Despite the presence of a normal BMI, leptin levels in KTP (25.2 +/- 3.6 ng/ml) and in HDP with chronic renal failure (25.3 +/- 4.2 ng/ml) were higher than in controls (11.7 +/- 1.8 ng/ml). The mean plasma NPY level in KTP (168.0 +/- 10.3 pg/ml) was significantly higher (p < 0. 01) than in controls (70.7 +/- 5.9 pg/ml) and in HDP (77.0 +/- 5.7 pg/ml). In all examined groups, a significant positive correlation was found between leptinaemia and BMI.. (1) KTP are characterized by significantly elevated leptinaemia in spite of a normal BMI. In KTP this increased leptinaemia does not seem to be dependent only upon the fat mass and the kind and dosis of immunosuppressive therapy. (2) Similarly to healthy subjects, female KTP and HDP show markedly higher leptinaemia than males. (3) In contrast to healthy subjects and HDP, KTP are characterized by significantly elevated plasma NPY levels.

Topics: Adult; Body Mass Index; Creatinine; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Neuropeptide Y; Proteins; Renal Dialysis; Statistics, Nonparametric

Elevated plasma concentrations of leptin, a hormone thought to regulate body composition by influencing food intake/metabolic rate, are prevalent in renal failure patients. The mechanism for these increases is not known, but evidence suggests that simple accumulation due to decreased elimination is insufficient explanation.. We studied the incidence of hyperleptinaemia in 28 end-stage renal disease patients treated with continuous ambulatory peritoneal dialysis (CAPD), compared with body-mass-index-and sex-matched controls. Results were separated by gender because women have higher leptin concentrations than men. Excretion of leptin and other substances in dialysis fluid was also studied.. Hyperleptinaemia was prevalent in women CAPD subjects, but not in men. Plasma leptin concentrations correlated strongly with the daily excretion of leptin in dialysis fluid. Clearance of leptin in dialysis fluid was greater in men than women CAPD subjects. Single regression analysis found that fasting insulin, glucose content of dialysis fluid, plasma albumin, C-reactive protein, erythropoietin dose, urinary creatinine clearance and plasma beta2-microglobulin were not determinants of plasma leptin concentrations. Stepwise forward multiple regression, examining the dependence of plasma leptin on body mass index, renal creatinine clearance, plasma albumin, daily dialysis fluid glucose load, daily leptin in dialysis fluid, erythropoietin dose and plasma C-reactive protein found only erythropoietin dose as a consistent negative predictor of plasma leptin concentrations.. The results suggest that hyperleptinaemia of CAPD was due to predisposing loss of renal elimination capacity combined with increased production due to obesity (more prevalent in women subjects of this study) and potentially female gender.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; C-Reactive Protein; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Proteins; Sex Factors

Leptin, the product of the obese gene, is produced exclusively in fat cells.. To evaluate the clinical significance of measuring serum leptin in 56 patients with chronic renal failure on hemodialysis (HD), we measured leptin levels using radioimmunoassay in 34 normal volunteers and in 56 patients on HD.. Normal serum leptin averaged 5.7 +/- 0.7 (mean +/- SEM) ng/ml, which correlated significantly (p < 0.001) with the body fat percentage as measured by bioelectrical impedance analysis. Serum leptin in HD patients ranged from 1.3 to 142 ng/ml. The mean serum leptin analyzed after the logarithmic conversion was 5.6 ng/ml, which was not significantly different from the normal control value, although the body fat percentage was significantly lower than normal volunteers. There was a significant (p < 0.01) positive correlation between body fat percentage and serum leptin in both normal controls and HD patients. The slope of the regression curve was steeper in HD patients than in normal controls.. (1) serum leptin levels to body fat mass are significantly higher in HD patients than controls; (2) the variability is much wider in HD patients; and (3) a significant relation exists between percent body fat and log serum leptin, the relation being steeper in HD patients than in controls.

Topics: Adipose Tissue; Adult; Aged; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Obesity; Proteins; Radioimmunoassay; Renal Dialysis

Topics: Adipose Tissue; Adult; Erythropoietin; Female; Humans; Injections, Intravenous; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Recombinant Proteins; Renal Dialysis

Elevated serum leptin can contribute to anorexia and poor nutrition in patients with chronic renal failure, because leptin is elevated in chronic renal failure patients with or without dialysis, especially in chronic ambulatory peritoneal dialysis (CAPD) patients. The aim of this study was to find whether leptin can be removed by peritoneal dialysis (PD) and to analyze factors that can affect serum leptin after start of CAPD by observing the change in serum leptin shortly after start of CAPD and its correlation with body mass index (BMI), with serum insulin, and with residual renal function.. Twenty patients who started CAPD during the observation period were studied. Serum leptin was measured by radioimmunoassay before start of CAPD, 3-5 days after start of CAPD, and 1 month and 3 months after start of CAPD. Simultaneously, body weight, serum insulin, and residual renal function were measured. To compensate for the circardian rhythm of leptin, removal of leptin was assessed by measuring dialysate leptin divided by average serum leptin before and after a peritoneal equilibration test (PET).. Leptin was eliminated by PD with a dialysate-to-serum ratio of 0.16+/-0.07, which was comparable to removal of beta2-microglobulin (0.14+/-0.06). The mean serum leptin concentrations did not decrease after 3-5 days of CAPD (8.4+/-13.1 ng/mL-->11.9+/-18.0 ng/mL) despite its removal by PD, and levels increased markedly to 189% of basal serum leptin 1 month after start of PD and to 260% of basal serum leptin 3 months after start of PD. Correlation coefficients (Spearman's rho) between change of serum leptin and change of BMI, of serum insulin, of glomerular filtration rate (average of urine creatinine clearance and urine urea clearance) were 0.267 (p > 0.05, n = 20), 0.441 (p > 0.05, n = 16), 0.706 (p > 0.05, n = 8) respectively.. Leptin is removed by peritoneal dialysis. Serum leptin did not decrease in 5 days after the start of PD despite its removal by PD, but increased markedly thereafter, within 3 months after start of PD. We could not find a significant correlation between the change in leptin and the change in BMI. Factors other than fat-mass gain can stimulate leptin increase shortly after start of PD.

Topics: Adipose Tissue; Body Weight; Female; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Proteins

Topics: Absorptiometry, Photon; Adult; Aged; Body Composition; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Parathyroid Hormone; Proteins; Radioimmunoassay; Regression Analysis; Renal Dialysis; Sex Factors; Triglycerides; Uremia

We performed a cross-sectional study in a wide sample of patients with chronic renal failure undergoing conservative therapy (CTh) (n = 79), peritoneal dialysis (PD) (n = 75), and hemodialysis (HD) (n = 51), with the aim of analyzing the impact of the different modes of therapy on serum leptin levels. We used a multivariate approach, taking into consideration the potential effects of other epidemiological, dialysis-related, nutritional, and hormonal factors on serum leptin. Leptin levels were higher in patients treated with PD (median, 36 ng/mL) than in those undergoing CTh (10.8 ng/mL) or HD (5.4 ng/mL) (P < 0.0005). This difference persisted after controlling for gender, body mass index, and fasting insulin levels, suggesting that imbalances in these factors may only partially explain the differences found between the three modes of therapy. Leptin levels showed a significant negative correlation with peritoneal protein losses in PD patients but were poorly associated with factors such as proteinuria, daily peritoneal glucose absorption (PD), renal function, or adequacy of dialysis. Leptin and insulin-like growth factor-I (IGF-I) were significantly correlated in PD patients, but the study design did not allow for establishing a meaning for this correlation. In conclusion, serum leptin levels are increased in PD patients when compared with CTh or HD patients. Differences in gender distribution, fat mass, and insulin levels may partially explain these findings, but other undefined factors also may have a role in producing these results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Female; Hemofiltration; Humans; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Kidney Function Tests; Leptin; Male; Membranes, Artificial; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis; Renal Dialysis; Uremia

The adipocyte-derived hormone leptin is the 16-kd product of the ob gene that regulates food intake and body weight. Plasma leptin level is elevated in patients with chronic renal failure, partly because of impaired clearance through the kidney. In this study, we examined whether leptin is cleared into peritoneal dialysate in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). The subjects were 46 CAPD patients and 67 age- and gender-matched healthy subjects. Leptin concentration in peritoneal dialysate from CAPD patients was measurable by a sensitive enzyme-linked immunosorbent assay (ELISA), and the daily loss of leptin by the peritoneal route was estimated to correspond to the amount contained in approximately 2 L plasma. Dialysate leptin concentration correlated positively with plasma leptin level and with percent body fat measured by dual-energy X-ray absorptiometry. The dialysate-to-plasma (D/P) ratio of leptin concentration was twice higher than expected from its molecular weight. D/P ratios of beta2-microglobulin, albumin, and transferrin showed strong correlations with each other (r = 0.768 to 0.801), whereas the correlation between D/P ratios of leptin and beta2-microglobulin was less impressive (r = 0.378). This was also the case with the relationship between apparent peritoneal clearances of these macromolecules, suggesting that dialysate leptin had some origins other than passive transport of plasma leptin. To test the hypothesis that abdominal visceral fat may contribute to the unexpectedly raised peritoneal dialysate leptin concentration, multiple regression analysis was performed. Leptin concentration in peritoneal dialysate showed significant association with plasma leptin level and D/P ratio of beta2-microglobulin, and it also showed an independent association with abdominal visceral fat but not with subcutaneous fat assessed by ultrasonography. These results showed that peritoneal dialysate from CAPD patients contained a significant amount of leptin, which derived presumably from both plasma and local visceral fat tissue.

Topics: Adipose Tissue; Body Composition; Dialysis Solutions; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Leptin is a 16-kd protein that increases energy expenditure and limits food intake. Serum leptin (S-leptin) is elevated in dialysis patients, and little data have been reported on leptin clearance (Cl) during dialysis. We analyzed the peritoneal dialysis (PD) Cl of leptin in 15 continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results to beta(2)-microglobulin (beta(2)-m), urea, and creatinine PD Cl. S-leptin was significantly elevated (Kruskal-Wallis, P < 0.005) in CAPD women (58.4 +/- 42.4 [SE] microg/L, n = 5) as compared with CAPD men (13.9 +/- 7.1, n = 10) and with healthy women (11.0 +/- 1.4, n = 13) and men (5.1 +/- 0. 9, n = 14). Correlations were found between percent of fat mass and S-leptin (P < 0.05); between S-leptin and the 24-hour PD leptin (P < 0.05); and between dialysate-to-plasma (D/P) beta(2)-m and D/P leptin (P < 0.01). PD leptin Cl (1.80 +/- 0.43 mL/min/1.73 m(2)) was higher than beta(2)-m Cl (1.22 +/- 0.31) (P < 0.01), but reduced as compared with urea Cl (8.84 +/- 1.20) (P < 0.005) and creatinine Cl (7.71 +/- 0.99) (P < 0.005). These results indicate that leptin is eliminated through the peritoneum membrane. However, peritoneal leptin clearance, as beta(2)-m, appears to be clearly restricted as compared with peritoneal transport of smaller molecules. Hence, leptin could use the same diffusion transport pathway as beta(2)-m. In addition, leptin, which has a higher molecular weight than beta(2)-m, was significantly more eliminated into the peritoneal dialysate. More studies are necessary to clarify whether this is an active leptin elimination process by peritoneal secretion or by a different restriction coefficient of diffusion through the peritoneum membrane.

Topics: Aged; beta 2-Microglobulin; Body Composition; Diffusion; Energy Metabolism; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Metabolic Clearance Rate; Middle Aged; Molecular Weight; Peritoneal Dialysis, Continuous Ambulatory

Topics: Animals; Appetite; beta 2-Microglobulin; Body Composition; Female; Humans; Hypothalamus; Kidney Failure, Chronic; Leptin; Male; Metabolic Clearance Rate; Peritoneal Dialysis; Satiety Response

Leptin serves an important role in suppressing appetite in mice and is known to be elevated in chronic renal failure (CRF) patients. But clinical significance of leptin as an appetite-reducing uremic toxin, remains to be determined. So we studied the relationship between plasma leptin and nutritional status in 46 chronic hemodialysis (HD) patients. Pre HD leptin was measured and divided by body mass index (BMI) to give adjusted leptin levels. KT/Vurea (K, dialyzer urea clearance; T, duration of HD; V, volume of distribution of urea), C-reactive protein (CRP), plasma insulin and nutritional parameters such as serum albumin, normalized protein catabolic rate (nPCR), subjective global assessment (SGA), BMI and mid-arm muscle circumference (MAMC) were also measured. Mean plasma leptin levels were 8.13+/-2.91 ng/mL (male 3.15+/-0.70; female 14.07+/-6.14, p<0.05). Adjusted leptin levels were positively correlated with nPCR (male r=0.47, p<0.05; female r=0.46, p<0.05), SGA (male r=0.43, p<0.05; female r=0.51, p<0.05) and MAMC (male r=0.60, p<0.005; female r=0.61, p<0.05). They did not correlate with KT/Vurea, serum albumin, hematocrit, bicarbonate, insulin and CRP. Presence of DM and erythropoietin therapy had no effect on leptin levels. These results suggest that leptin is a marker of good nutritional status rather than a cause of protein energy malnutrition in chronic HD patients.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutrition Disorders; Nutritional Status; Obesity; Renal Dialysis; Sex Factors

Iseki et al. [1] have shown that serum levels of albumin (Alb), creatinine (Cr) and BMI are significant predictors of death in haemodialyzed patients (HD pts). In our study we decided to assess the relationship between the levels of Alb, Cr, BMI and substances which have a known metabolic effect on nutritional status in HD pts: endogenous erythropoietin (Epo), insulin-like growth factor-1 (IGF-1), leptin (Lep), parathormone (PTH), and testosterone. The study was conducted in 53 (28M, 25F) stable HD pts. Serum levels of endogenous Epo and PTH were estimated by CLIA; IGF-1, Lep, testosterone, sex hormone binding globulin were estimated by RIA. The multiple regression analysis was done between Alb, Cr, BMI and Epo, IGF-1, PTH and Lep for all HD pts together and free androgen index (FAI) for men and women separately. Correlations: the level of serum albumin did not correlate significantly with any of the measured substances. Serum creatinine level significantly correlated only with the level of IGF-1 (p=0.02), BMI was significantly correlated with serum endogenous Epo (p<0.01), leptin (p=0.004) and FAI (p<0.005) both in men and women. We concluded that the higher concentrations of endogenous Epo, IGF-1 and testosterone could be correlated with a better prognosis in HD patients.

Topics: Adult; Aged; Biomarkers; Erythropoietin; Female; Humans; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Parathyroid Hormone; Prognosis; Radioimmunoassay; Renal Dialysis; Testosterone

Leptin is a newly found hormone secreted by adipocytes that regulates food intake, thermogenesis, and body fat. We measured plasma leptin levels in 103 patients with chronic renal failure treated by hemodialysis and 167 age- and gender-matched healthy control subjects to examine the impact of renal failure on plasma leptin levels and the influence of leptin on body composition measured by dual-energy X-ray absorptiometry. Hemodialysis patients showed a significant decrease in both body fat mass and lean body mass compared with those of the control subjects. Plasma leptin was significantly elevated in the hemodialysis group over the controls. In both groups, leptin was higher in female than male subjects, and it correlated positively with percent body fat. The subjects were divided into six categories according to percent body fat, and plasma leptin levels were compared between the two groups in the same category. Leptin of hemodialysis patients was significantly higher than that of the control subjects in the percent body fat categories of 30 or greater, whereas there was no statistically significant difference in leptin concentrations in the lower percent body fat categories. This was also true in the comparison in each gender, and leptin levels in female subjects showed a more remarkable difference between the hemodialysis and control groups in obese categories. Multiple regression analysis in all subjects indicated that plasma leptin levels were independently affected by percent body fat, plasma insulin concentration, gender, and renal failure. The positive impact of renal failure on leptin remained significant in the subjects with percent body fat of 30 or greater in the multiple regression model, whereas it was no longer significant in the remaining lean subjects. In multiple regression analysis of factors affecting fat mass index and lean mass index, leptin level was selectively associated with fat mass index, but not with lean mass index, regardless of percent body fat ranges. These results indicate that renal failure is an important factor affecting plasma leptin levels, especially in obese female subjects, and that hyperleptinemia was closely related to fat mass but not to lean body mass in hemodialysis patients.

Topics: Body Composition; Body Mass Index; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay; Regression Analysis; Renal Dialysis

Topics: Adipose Tissue; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Kidney Failure, Chronic; Leptin; Middle Aged; Proteins; Recombinant Proteins

Decreased spontaneous nutrient intake is a frequent clinical problem in patients with chronic renal failure (CRF). Leptin, the recently characterized gene product of the obese gene, is produced by adipocytes and is thought to act as an afferent satiety signal on the appetite and satiety centers of the brain. Serum leptin levels were investigated in 134 pediatric patients in different stages of CRF to evaluate a possible relationship between leptin, GFR, and spontaneous energy intake. Serum leptin levels, measured by a specific RIA, were elevated above the 50th percentile of the normal range in 78% of CRF patients and above the 95th percentile in 45% of patients. Gel chromatography of CRF sera yielded only one single immunoreactive peak at 16 kD, indicating that the increase of immunoreactive leptin levels in CRF serum was not due to accumulation of leptin degradation products. Multiple stepwise regression analysis revealed the percentage of body fat as assessed from skinfold measurements (r = 0.79, P < 0.0001) and GFR (r = -0.17, P < 0.005) as independent predictors of serum leptin levels, accounting for 66% of total statistical variability. There was an inverse linear correlation between standardized leptin levels (leptin z-score) and the spontaneous energy intake quantified from written dietary diaries (r = -0.36, P < 0.001). These data suggest that the percentage of body fat remains the main determinant of serum leptin in CRF patients, but their levels increase with declining GFR, presumably by reduced renal clearance. Leptin levels in CRF serum that are inappropriately elevated in relation to the percentage of body fat might lead to a dysregulation of the normal peripheral-central leptin feedback loop, thereby contributing to decreased nutrient intake in uremia.

Topics: Adolescent; Adult; Body Composition; Body Mass Index; Child; Child, Preschool; Energy Intake; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Leptin; Male; Proteins; Reference Values; Skinfold Thickness

Serum leptin concentrations in normal humans have been reported to correlate with the body mass index (BMI) as well as with the body fat mass. In this study, we measured serum leptin concentrations in 107 patients on hemodialysis, 30 of whom had diabetes mellitus as the cause, and examined the clinical significance. Furthermore, we evaluated the effects of high-flux dialysis membranes on serum leptin levels. Serum leptin concentrations had a linear correlation with BMI as well as with the percentage of body fat in patients on hemodialysis. The serum leptin concentrations showed a positive correlation with the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglyceride, the body weight, the BMI, and the percentage of body fat. The serum leptin levels were not different between the diabetic and the nondiabetic groups. The serum leptin levels in the nondiabetic group were nearly fourfold higher in women than in men. We investigated the differences in the rate of reduction in serum leptin after dialysis with polysulfone membrane dialyzers (PS-N and PS-UW) in comparison with a cellulose membrane dialyzer (AM-SD), and as a result, we found that the polysulfone membrane dialyzers removed serum leptin, while the cellulose membrane dialyzer did not. We conclude that in patients on hemodialysis, the serum leptin concentration is a valuable clinical marker of the body fat content and may also contribute to the evaluation of hyperlipidemia.

Topics: Adipose Tissue; Aged; Body Mass Index; Body Weight; Diabetic Nephropathies; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Regression Analysis; Renal Dialysis; Sex Characteristics

Previous studies have reported that patients with end-stage renal disease (ESRD) have elevated plasma leptin concentrations, but the cause and significance of the elevations are unknown. We studied leptin concentrations in 29 adults undergoing renal transplantation, to determine if restoration of renal function reduced leptin concentrations in ESRD.. Leptin concentrations were measured by radioimmunoassay in plasma specimens collected within 1 week before transplant, 6 days post-transplant, and 60 days post-transplant.. Mean plasma leptin concentrations were higher in both male and female ESRD patients compared with a control population of similar age and body mass index (BMI), but most of the disparity was due to a minority of patients with grossly elevated concentrations; the majority of ESRD patients had normal or near-normal leptin concentrations after accounting for their adiposity with BMI. Six days after successful renal transplantation, average plasma leptin concentrations decreased to control levels. The grossly elevated pretransplant concentrations in a minority of patients were greatly reduced in relation to BMI, and the reduction persisted to 60 days post-transplant. The decrease in creatinine with transplant did not correlate with the decrease in leptin.. These results demonstrate that restoration of renal function in ESRD patients reduces hyperleptinaemia, which provides further evidence of a cause/effect relationship between impaired renal function and abnormal leptin metabolism.

Topics: Adult; Aged; Body Mass Index; Creatinine; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Middle Aged; Osmolar Concentration; Postoperative Period; Proteins; Treatment Outcome

The ob gene product leptin is thought to be a key regulator of food intake and body weight. Patients having advanced chronic renal failure (CRF) have markedly higher serum leptin levels. It is not known whether the increase in leptin levels in CRF is caused by a decreased plasma clearance and/or increased production.. In the present study serum leptin levels and glomerular filtration rate (GFR) were measured in 219 patients having various degrees of renal failure. In addition, serum leptin levels, C-reactive protein (CRP), body composition (by dual-energy x-ray absorptiometry) and ob gene expression (by in situ hybridization histochemistry) were determined in 15 patients with advanced CRF. Seven of the patients were re-evaluated following 12 months of peritoneal dialysis (PD) treatment.. Serum leptin levels correlated negatively to GFR (r = -0.26; P < 0.0001). The ob gene expression was significantly lower in patients with CRF than in healthy controls. A negative correlation between serum leptin levels and ob gene expression (r = -0.66; P < 0.05) was found in patients with CRP < 25 mg/liter. The ob gene expression (20.0 +/- 1.8 vs. 15.0 +/- 1.0 nCi/g; P < 0.05) was significantly higher in 5 patients with CRP > 25 mg/liter than in 10 patients with CRP < 25 mg/liter. Following 12 months of PD, the amount of body fat increased by 30% while the ob gene expression remained unchanged.. The present study shows a correlation between serum leptin levels and GFR, and our results suggest that elevated leptin levels, due to a decreased plasma clearance, down-regulate the expression of the ob gene. We also found that an ongoing inflammation stimulates ob gene expression in patients with CRF. Therefore, it is suggested that the hyperleptinemia induced feedback inhibition of ob gene expression is overcome by inflammatory cytokines.

Topics: Adipose Tissue; Adult; Aged; Aged, 80 and over; Case-Control Studies; Down-Regulation; Feedback; Female; Gene Expression; Glomerular Filtration Rate; Humans; Inflammation; Inflammation Mediators; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Obesity; Peritoneal Dialysis; Proteins

To determine the relationship between plasma leptin and insulin-like growth factor-I (IGF-I) levels in healthy subjects and patients with chronic renal insufficiency at baseline, and during administration of recombinant human IGF-I in the renal impaired patients.. 20 healthy subjects (six men, 14 women, age: 42.7 +/- 3.2 y) and nine subjects with chronic renal insufficiency (five men, four women, age: 53.6 +/- 3.7 y).. Daily s.c. injection of recombinant human IGF-I (50 micrograms/kg) for 24 d.. Fasting plasma levels of leptin, IGF-I, growth hormone, C-peptide, glucagon and IGF binding proteins by specific radioimmunoassays at baseline in all subjects and serially during IGF-I therapy in the renal impaired subjects.. Baseline leptin levels were correlated with body mass index (BMI, R = 0.72, P = 0.0001) but not IGF-I levels (R = 0.02). During IGF-I therapy, plasma IGF-I levels increased from 128 +/- 17.4 ng/ml at baseline to 250 +/- 36.8 ng/ml on day 3 (P = 0.003) and 323 +/- 61.6 ng/ml on day 24 (P = 0.01), whereas leptin levels declined: 24.4 +/- 10.3 ng/ml (baseline), 19.5 +/- 6.2 ng/ml (day 3, P = 0.028), and 17.2 +/- 4.9 ng/ml (day 24, P = 0.05).. Basal plasma leptin and IGF-I levels are not correlated; however, chronic administration of recombinant IGF-I is associated with an early and sustained decrease in plasma leptin levels. IGF-I may have an inhibitory effect on leptin secretion in humans.

Topics: Adult; Binding Sites; Body Mass Index; C-Peptide; Female; Glucagon; Humans; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay; Receptor, IGF Type 1; Receptors, Leptin; Recombinant Proteins

Leptin is a protein produced by fat cells and involved in body weight regulation. Plasma leptin is significantly higher in some hemodialysis (HD) patients than in normal controls. We examined the influence of dialyzer membrane biocompatibility and flux on elevated plasma leptin concentrations in hemodialysis patients. Employing a crossover design, leptin and tumor necrosis factor-alpha (TNF-alpha) levels were serially determined in eight chronic dialysis patients. Patients were dialyzed sequentially on low-flux cellulosic (TAF) dialyzers, low-flux (F8) polysulfone, high-flux (F80B) polysulfone, then low-flux polysulfone and cellulosic dialyzers again. Mean leptin concentrations were similar when low-flux polysulfone or cellulosic dialyzers were employed (141.9+/-24.2 microg/L versus 137.8+/-18.4 microg/L, respectively (P=NS). In contrast, leptin fell significantly on the high-flux polysulfone dialyzer (99.4+/-16.2 microg/L) compared with cellulosic (P < 0.005), and low-flux polysulfone dialyzers (P < 0.02). Leptin clearance by the high-flux polysulfone dialyzer was significantly higher than the low-flux dialyzers (50.4+/-21.5 v -9.6+/-10.3 mL/min; P=0.043), but did not account fully for the 30% decline in plasma leptin during the high-flux arm of the study. Concentrations of TNF-alpha were lower when high-flux polysulfone dialyzers were employed, but there was no correlation of individual TNF-alpha levels with leptin concentrations. High-flux dialysis lowers plasma leptin concentrations an average of 30%, but biocompatibility does not influence leptin levels. The decrease in plasma leptin on high-flux dialysis cannot be explained solely by enhanced clearance.

Topics: Cross-Over Studies; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay; Renal Dialysis; Tumor Necrosis Factor-alpha

Leptin is a 16-kDa protein recently identified as the obese gene product involved in body weight regulation. Administration of recombinant leptin to ob/ob mice, which have a genetic defect in leptin production, reduces food intake and increases energy expenditure. Leptin is synthesized by fat cells, and in normal humans, plasma concentrations are proportional to adiposity. The physiological actions and the degradation pathways of leptin in humans are unknown. We investigated renal elimination of leptin by comparing plasma leptin concentrations in end-stage renal disease (ESRD) patients with normal controls. Our hypothesis was that if renal filtration is a significant route of elimination, the hormone would accumulate in ESRD patients. Mean plasma levels in 141 ESRD patients (26.8 +/- 5.7 and 38.3 +/- 5.6 micrograms/L for males and females, respectively) were significantly higher (P < 0.001) than mean values obtained in normal controls (11.9 +/- 3.1 and 21.2 +/- 3.0 micrograms/L for males and females, respectively). Leptin concentrations in ESRD patients correlated directly with body mass index (BMI; r = 0.77 for men and 0.78 for women). The rate of increase in leptin concentrations with BMI was significantly greater in ESRD patients (5.5 and 6.6 micrograms/L/U BMI for men and women, respectively) than in normal controls (1.4 and 2.6 micrograms/L/U for men and women, respectively). Pre- and postdialysis leptin levels in hemodialysis patients were similar. Western blot of plasma from ESRD patients with high leptin levels showed bands corresponding to the intact protein (16 kDa) with no lesser or greater molecular mass species observed. Leptin concentrations in patients with ESRD did not correlate with measures of residual renal function (serum creatinine, beta 2-microglobulin, PTH, or GH levels). Similarly, we found no correlation between leptin levels and the number of years patients had been on dialysis or with recent weight changes. We conclude that intact leptin is increased in ESRD patients, but does not appear to cause decreased weight. As leptin levels did not correlate with residual renal function, increased production may account for the high levels observed.

Topics: Adult; Aged; Aged, 80 and over; Blotting, Western; Body Mass Index; Female; Humans; Kidney; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Osmolar Concentration; Proteins; Renal Dialysis

Leptin, the gene product of the ob gene, is important in the control of appetite in rodents and may have an important role in humans. The clearance of leptin from the circulation is unknown. As the leptin receptor is present in the kidney, we evaluated the role of the kidney in removing circulating leptin in humans. We measured leptin in aortic and renal vein plasma in 8 patients with intact renal function and 6 patients with impaired renal function who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. In patients with intact renal function there is net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal failure on hemodialysis, peripheral leptin levels factored for body mass index was increased by > fourfold as compared to a group of healthy controls (N = 338). In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Additional studies are required to evaluate the role of leptin in mediating the anorexia of uremia.

Topics: Aged; Aorta; Blood; Cohort Studies; Female; Humans; Kidney; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Renal Circulation; Renal Dialysis; Renal Veins

The ob gene product leptin is secreted by fat cells and reflects the content of fat in the body. Leptin and insulin concentrations as well as body weight are interrelated and a direct correlation has been found between these concentrations in humans with normal renal function. Markedly elevated serum leptin concentrations have recently been reported in patients with chronic renal failure (CRF). The aim of the present study was to investigate the relation between serum leptin and plasma insulin in patients with advanced CRF.. Serum leptin, plasma insulin, as well as body fat content (determined with dual-energy X-ray absorptiometry) were determined in a cohort of 46 patients (mean age 54 +/- 2 years) with advanced CRF (creatinine clearance 8 +/- 1 ml/min).. In 23 CRF patients with plasma insulin below the median value (14 mU/l), serum leptin concentrations were no higher than in healthy controls (8.0 +/- 1.2 vs 8.4 +/- 0.9 ng/ml). However, in CRF patients with plasma insulin > 14 mU/l (n = 23) the serum leptin concentrations were much higher (38.2 +/- 11.0 ng/ml; P < 0.0001). In CRF patients, serum leptin (normalized for the per cent body fat content) correlated significantly (r = 0.64; P < 0.0001) with plasma insulin concentrations. However, the increase in plasma insulin was blunted in patients with very high serum leptin concentrations in relation to the per cent body fat content.. The present results demonstrate that serum leptin concentrations are markedly elevated in CRF patients with higher plasma insulin than in those with lower plasma insulin concentrations. This suggests that insulin resistance and hyperinsulinaemia contribute to elevated serum leptin concentrations in CRF. The present results also demonstrate that, when circulating serum leptin concentrations are much higher in relation to the per cent body fat content, no additional increase in plasma insulin occurs. This latter observation suggests that the secretion of insulin by the pancreas is lower in hyperleptinaemic patients. Consequently, extremely elevated serum leptin may play a role in reducing glucose-stimulated insulin secretion and glucose intolerance in CRF.

Topics: Adipose Tissue; Adult; Aged; Cross-Sectional Studies; Female; Humans; Insulin; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins

Leptin, secreted from fat cells, functions as a lipostat mechanism through modulation of satiety signals. The role of leptin in humans has been only partly revealed. However, obese patients have markedly elevated levels of this hormone, and in both normal-weight and obese subjects there is a direct correlation between serum leptin levels and the percentage of body fat. The aim of the present study was to investigate the role of leptin and its relation to body fat content in chronic renal failure (CRF), a disorder associated with decreased appetite. Serum leptin levels and body composition (dual-energy x-ray absorptiometry) were measured in a cohort of 59 patients with terminal CRF (creatinine clearance rate, 8 +/- 1 ml/min). Sixteen of the patients were re-evaluated after 12 mo of peritoneal dialysis treatment, and eight patients were re-evaluated after 12 mo of hemodialysis treatment. The mean serum leptin concentrations were markedly higher (mean +/- SEM) in patients with CRF than in healthy control subjects matched for gender and body mass index (25.7 +/- 5.2 ng/ml versus 8.4 +/- 0.9 ng/ml; P < 0.001). Patients with ongoing signs of inflammation (C-reactive protein > 10 mg/L) demonstrated higher serum leptin levels (41.9 +/- 13.7 ng/ml versus 18.6 +/- 4.2 ng/ml; P < 0.05) than patients with normal C-reactive protein. A strong positive correlation (rho = 0.83; P < 0.0001) was found between serum leptin concentrations and the percentage of body fat. After 12 mo of peritoneal dialysis, the amount of body fat increased markedly (19.0 +/- 1.5 to 25.1 +/- 2.2 kg; P < 0.001), and the changes in serum leptin concentrations correlated significantly (rho = 0.69; P < 0.01) to the changes in the body fat content. In contrast, no significant changes in either body fat content or serum leptin levels were recorded in the eight patients that were re-evaluated after 12 mo of hemodialysis. Serum leptin concentrations are approximately three times higher in patients with CRF compared with healthy control subjects with a similar body mass index. In this study, it is also demonstrated that serum leptin is a good marker for the body fat content in CRF patients and correlates strongly to changes in body fat during 12 mo of peritoneal dialysis. These findings suggest that serum leptin could serve as a valuable clinical marker for the body fat content in patients with CRF. Further studies are needed to verify the hypothesis that increased serum leptin concentrations may contri

Topics: Adipose Tissue; Adult; Aged; Body Composition; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Leptin; Longitudinal Studies; Male; Middle Aged; Osmolar Concentration; Peritoneal Dialysis; Prospective Studies; Proteins; Renal Dialysis

1. Leptin is thought to be an inhibitor of appetite. As the kidney helps clear several polypeptide hormones, plasma leptin may accumulate in end-stage renal disease. 2. Plasma immunoreactive leptin was measured in four groups of subjects: haemodialysis, continuous ambulatory peritoneal dialysis and renal transplant patients and a group of healthy controls. Leptin was also measured before and after a single dialysis session. 3. There was a strong correlation between plasma immunoreactive leptin and body mass index in all groups except female haemodialysis patients. Leptin was higher in females than in males in all groups when controlled for body mass index. Mean plasma leptin [mean (SD)] was significantly higher in all renal groups [haemodialysis, 15.1 (3.6) ng/ml; continuous ambulatory peritoneal dialysis, 25.4 (4.3) ng/ml; transplants, 11.6 (2.6) ng/ml] compared with controls [5.3 (2.3) ng/ml]. There was a significant difference in the regression equations relating leptin and body mass index (dialysis > transplants > controls), even when controlled for gender. Leptin correlated modestly with serum creatinine in non-dialysis subjects. Plasma leptin immunoreactivity was slightly reduced by haemodialysis, but post-dialysis leptin was still significantly higher than that found in controls. 4. Chromatographic characterization of the high level of leptin immunoreactivity found in haemodialysis subjects showed a single elution peak corresponding to that of the highly purified human leptin standard. 5. In conclusion, leptin is higher than expected for body mass index in end-stage renal disease. Hyperleptinaemia could contribute to the anorexia and poor nutritional status commonly seen in renal failure.

Topics: Adult; Aged; Analysis of Variance; Body Mass Index; Chromatography, Gel; Female; Humans; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Proteins; Regression Analysis; Renal Dialysis

Protein-energy malnutrition occurs in patients with chronic renal failure primarily due to loss of appetite. The ob gene protein, leptin, which is secreted by adipocytes, regulates body composition by lowering food intake. We have measured plasma leptin in undialysed and dialysed patients and in controls and the concentrations have been related to body composition, dietary intake, and biochemistry.. Plasma leptin was measured by radioimmunoassay in 93 individuals in groups of undialysed, peritoneal dialysed, and haemodialysed patients and controls. Body composition was determined by DEXA.. Protein-energy malnutrition was evident in non-dialysed and dialysed patients from low lean or fat tissues, plasma albumin and transferrin. A third of the dialysis patients were eating less than prescribed intakes. Leptin relative to total fat mass (ng/ml/kg) was significantly greater for patients than for controls, particularly the dialysed patients. Leptin was highly correlated with total, arm, leg, and all other fat measurements, e.g. r for leptin vsm % total fat was: undialysed 0.88, PD 0.81, HD 0.93, and controls 0.83 (P < 0.0001 for all). Dialysis patients with the highest leptin/fat mass ratio had low protein intakes and significantly lower lean tissue mass. Leptin/fat ratio correlated inversely with dietary intake e.g. with protein intake in g/day and marginally in g/kg of ideal weight/day. Leptin concentration was unrelated to plasma creatinine or residual renal function or to the protein 'nutritional indices', albumin and transferrin.. Our data suggests that leptin is markedly increased in some patients with chronic renal failure. The association of increased leptin with low protein intake and loss of lean tissue is consistent with leptin contributing to malnutrition but a definitive role cannot be substantiated by this study.

Topics: Aged; Body Composition; Dietary Proteins; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Nutrition Disorders; Peritoneal Dialysis; Proteins; Renal Dialysis

Topics: Adipocytes; Animals; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glycation End Products, Advanced; Glycosylation; Humans; Hypoglycemic Agents; Kidney Failure, Chronic; Leptin; Metformin; Mice; Mice, Mutant Strains; Mice, Obese; Obesity; Protein Biosynthesis; Proteins

To investigate the mechanism(s) of degradation of leptin, the protein product of ob (obese) gene, we measured serum leptin levels in 70 patients with chronic renal failure (CRF). The median of serum leptin concentrations of 36 male and 34 female patients with CRF were 7.3 ng/ml ranging from 0.5 to 39.0 ng/ml and 34.9 ng/ml from 1.1 to 76.1 ng/ml, respectively, while those of 29 male and 29 female healthy subjects were 5.8 ng/ml ranging from 0.5 to 37.7 ng/ml and 12.0 ng/ml from 2.0 to 45.2 ng/ml, respectively. The difference in male and female serum leptin concentrations between CRF group and the normal counterpart was statistically significant (p<0.005 and p<0.05, respectively). However, there was no significant correlation, either between serum creatinine or BUN, and serum leptin concentrations. These findings suggest that leptin is degraded and/or filtered in renal tissue.

Topics: Adult; Aged; Aged, 80 and over; Blood Urea Nitrogen; Body Mass Index; Creatinine; Female; Humans; Kidney Failure, Chronic; Leptin; Male; Middle Aged; Proteins; Reference Values