leptin and Renal-Insufficiency--Chronic

Leptin is an adipokine that regulates appetite and body mass and has many other pleiotropic functions, including regulating kidney function. Increased evidence shows that chronic kidney disease (CKD) is associated with hyperleptinemia, but the reasons for this phenomenon are not fully understood. In this review, we focused on potential causes of hyperleptinemia in patients with CKD and the effects of elevated serum leptin levels on patient kidney function and cardiovascular risk. The available data indicate that the increased concentration of leptin in the blood of CKD patients may result from both decreased leptin elimination from the circulation by the kidneys (due to renal dysfunction) and increased leptin production by the adipose tissue. The overproduction of leptin by the adipose tissue could result from: (a) hyperinsulinemia; (b) chronic inflammation; and (c) significant lipid disturbances in CKD patients. Elevated leptin in CKD patients may further deteriorate kidney function and lead to increased cardiovascular risk.

Topics: Adipose Tissue; Female; Gene Expression; Gene Expression Regulation; Humans; Kidney; Leptin; Male; Receptors, Leptin; Renal Insufficiency, Chronic

The importance of cardiometabolic factors in the inception and progression of atherosclerotic cardiovascular disease is increasingly being recognized. Beyond diabetes mellitus and metabolic syndrome, other factors may be responsible in patients with chronic kidney disease (CKD) for the high prevalence of cardiovascular disease, which is estimated to be 5- to 20-fold higher than in the general population. Although undefined uremic toxins are often blamed for part of the increased risk, visceral adipose tissue, and in particular epicardial adipose tissue (EAT), have been the focus of intense research in the past two decades. In fact, several lines of evidence suggest their involvement in atherosclerosis development and its complications. EAT may promote atherosclerosis through paracrine and endocrine pathways exerted via the secretion of adipocytokines such as adiponectin and leptin. In this article we review the current knowledge of the impact of EAT on cardiovascular outcomes in the general population and in patients with CKD. Special reference will be made to adiponectin and leptin as possible mediators of the increased cardiovascular risk linked with EAT.

Topics: Adiponectin; Adipose Tissue; Cardiovascular Diseases; Humans; Leptin; Pericardium; Renal Insufficiency, Chronic

Chronic kidney disease (CKD) patients have an extremely high risk of developing cardiovascular diseases (CVD) compared to the general population. Systemic inflammation associated with oxidative stress could be an important determinant of morbidity and mortality associated with CVD. We suspected that dysregulation of iron metabolism should be considered in these patients. Anemia is prevalent in CKD patients and is often treated with erythropoiesis-stimulating agents (ESAs) and iron. In addition, iron administration sometimes causes iron overdose. Excessive iron in the cytosol and mitochondria can accelerate the formation of a highly toxic reactive oxygen species, hydroxyl radicals, which damage lipids, proteins, and DNA. In this review, we propose the following four major reasons for oxidative stress in CKD patients: 1) iron is sequestered in cells by proinflammatory cytokines and hepcidin; 2) the reduction in frataxin increases "free" iron in mitochondria; 3) the accumulation of 5-aminolevulinic acid, a heme precursor, has toxic effects on iron and mitochondrial metabolism; and 4) the elevated levels of the metabolic hormone, leptin, promote hepatic hepcidin production. Although an efficient therapy for preventing oxidative stress in these patients has not yet been well defined, we propose that ESAs for renal anemia may ameliorate these causes of oxidative stress. Further clinical trials are necessary to clarify the effectiveness of ESAs on oxidative stress in CKD patients.

Topics: Aminolevulinic Acid; Anemia; Hematinics; Heme; Hepcidins; Humans; Inflammation; Iron; Iron Overload; Leptin; Mitochondria; Oxidative Stress; Renal Insufficiency, Chronic

Chronic kidney diseases (CKD), a common outcome of various kidney diseases, cause a series of refractory complications, which lead to great economic burdens on patients. The clinical outcomes of CKD depend on various factors, including metabolic disorders. Leptin, a peptide hormone, produced in adipose tissues, plays an important role in regulating food consumption and energy expenditure. Leptin also influences the immune system and hematopoiesis. Increased leptin status is observed in CKD, leptin deficiency attenuates the immune response in nephritis. Conversely, leptin inhibits the development of obesity, which is closely associated glomerular disorder. Now, the precise role of leptin in CKD remains elusive. This review will give an integrated understanding of the potential role of leptin and its interactions with other signal molecules in CKD.

Topics: Animals; Humans; Leptin; Models, Biological; Renal Insufficiency, Chronic; Signal Transduction

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin-angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.

Topics: Animals; Child Development; Disease Models, Animal; Fetal Growth Retardation; Humans; Hypertension; Infant Nutritional Physiological Phenomena; Infant, Low Birth Weight; Infant, Newborn; Leptin; Metabolic Networks and Pathways; Neuropeptide Y; Nutritional Status; Renal Insufficiency, Chronic; Renin-Angiotensin System

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase.

Topics: Aldosterone; Animals; Antihypertensive Agents; Dyslipidemias; Heart Conduction System; Hemodynamics; Humans; Hypertension; Insulin Resistance; Intra-Abdominal Fat; Kidney; Leptin; Metabolic Syndrome; Models, Animal; Models, Cardiovascular; Natriuresis; Obesity; Organ Specificity; Parasympathetic Nervous System; Pressure; Prevalence; Pro-Opiomelanocortin; Receptors, Leptin; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

Anemia, dyslipidemia, malnutrition, together with mineral and bone disorders are common complications in patients with chronic kidney disease (CKD). All are associated with increased risk of mortality. Leptin is a small peptide hormone that is mainly but not exclusively produced in adipose tissue. It is also secreted by normal human osteoblasts, subchondral osteoblasts, placental syncytiotrophoblasts, and the gastric epithelium. Leptin binds to its receptors in the hypothalamus to regulate bone metabolism and food intake. Leptin also has several other important metabolic effects on peripheral tissues, including the liver, skeletal muscle, and bone marrow. Leptin is cleared principally by the kidney. Not surprisingly, serum leptin appears to increase concurrently with declines in the glomerular filtration rate in patients with CKD. A growing body of evidence suggests that leptin might be closely related to hematopoiesis, nutrition, and bone metabolism in CKD patients. Results are conflicting regarding leptin in patients with CKD, in whom both beneficial and detrimental effects on uremia outcome are found. This review elucidates the discovery of leptin and its receptors, changes in serum or plasma leptin levels, the functions of leptin, relationships between leptin and the complications mentioned above, and pharmaceutical interventions in serum leptin levels in patients with CKD.

Topics: Anemia; Bone and Bones; Bone Diseases, Metabolic; Dyslipidemias; Hematopoiesis; Humans; Leptin; Malnutrition; Nutritional Status; Receptors, Leptin; Renal Insufficiency, Chronic

White adipose tissue secretes a large variety of compounds named adipokines amongst which, leptin exhibits pleiotropic metabolic actions. Leptin is an anorexigenic hormone, secreted in proportion of fat mass, with additional effects on the regulation of inflammation, cardiovascular system, immunity, hematopoiesis and bone metabolism. Chronic kidney disease (CKD) is characterized by an increase of plasma leptin concentration that may be explained by a lack of renal clearance. Hyperleptinemia plays a key role in the pathogenesis of complications associated with CKD such as cachexia, protein energy wasting, chronic inflammation, insulin resistance, cardiovascular damages and bone complications. Leptin is also involved in the progression of renal disease through its pro-fibrotic and pro-hypertensive actions. Most of the adverse effects of leptin have been documented both experimentally and clinically. Leptin may therefore be considered as an uremic toxin in CKD. The aim of this review is to summarize the pathophysiological and clinical role of leptin in in vitro studies, experimental models, as well as in patients suffering from CKD.

Topics: Adipose Tissue; Cachexia; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Receptors, Leptin; Renal Insufficiency, Chronic; Toxins, Biological

Ghrelin is an orexigenic hormone with additional effects on the regulation of inflammation and the cardiovascular system. It may play an important role in the pathogenesis of cachexia/protein-energy wasting (PEW), inflammation and cardiovascular complications in chronic kidney disease (CKD). There are three circulating gene products of ghrelin, namely, acyl ghrelin, des-acyl ghrelin and obestatin, each with individual distinct functions. Perturbations of these circulating ghrelin proteins impact the overall milieu of CKD. Leptin is an anorexigenic hormone which is secreted from the adipocytes and interacts with ghrelin and other appetite-regulating hormones. Leptin also plays a role in regulating inflammation and the cardiovascular system. Indeed, ghrelin and leptin may play yin-and-yang roles in CKD pathophysiology. Clinical trials involving the use of the mimetics or antagonists of these hormones are limited to short-term phase I/II studies. Further understanding of their interactions in CKD pathophysiology is needed for potential large-scale clinical trials, which may impact the quality of life and survival of patients with CKD.

Topics: Animals; Appetite Regulation; Body Weight; Cardiovascular Diseases; Disease Progression; Ghrelin; Humans; Inflammation; Kidney; Leptin; Malnutrition; Prognosis; Renal Insufficiency, Chronic; Signal Transduction

The adipocyte product leptin is a pleiotropic adipokine and hormone, with a role extending beyond appetite suppression and increased energy expenditure. This review summarizes the biology of the leptin system and the roles of its different receptors in a multitude of cellular functions in different organs, with special emphasis on the kidney. Leptin's physiological functions as well as deleterious effects in states of leptin deficiency or hyperleptinemia are emphasized. Chronic hyperleptinemia can increase blood pressure through the sympathetic nervous system and renal salt retention. The concept of selective leptin resistance in obesity is emerging, whereby leptin's effect on appetite and energy expenditure is blunted, with a concomitant increase in leptin's other effects as a result of the accompanying hyperleptinemia. The divergence in response likely is explained by different receptors and post-receptor activating mechanisms. Chronic kidney disease is a known cause of hyperleptinemia. There is an emerging view that the effect of hyperleptinemia on the kidney can contribute to the development and/or progression of chronic kidney disease in selective resistance states such as in obesity or type 2 diabetes mellitus. The mechanisms of renal injury are likely the result of exaggerated and undesirable hemodynamic influences as well as profibrotic effects.

Topics: Appetite Regulation; Energy Metabolism; Humans; Kidney; Leptin; Receptors, Leptin; Renal Insufficiency, Chronic

Increased evidence suggests that obesity-related glomerulopathy and chronic kidney diseases should be identified as isolated complications of obesity. It is questioned if the numerous adipose tissue productions could play a role in the initiation/maintenance of such kidney diseases. This review will provide a sum-up of recent advances on fat cell metabolism and adipose tissue physiology. The adipose tissue behaves as an endocrine organ with multiple activities. It is secreting hormones (leptin, adiponectin, apelin) and numerous factors with autocrine, paracrine and systemic effects. These secretions are coming from adipocytes themselves or from cells present in the stroma-vascular fraction of the adipose tissue. When expanding, the adipose tissue of the obese is infiltrated by immune cells such as macrophages and lymphocytes; the role of which is not fully clarified. An attempt will be done to delineate if alterations of lipid storage/fatty acid release or of the secretion potencies of adipose tissue could contribute to kidney lipotoxicity and other chronic kidney diseases described in the obese.

Topics: Adipocytes; Adiponectin; Adipose Tissue, White; Apelin; Biomarkers; Body Mass Index; Cytokines; Evidence-Based Medicine; Glomerulonephritis; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Metabolic Syndrome; Obesity; Renal Insufficiency, Chronic

Adipose tissue is now considered to be an active physiologic system operating in concert with multiple other organs. Leptin is a peptide hormone that is primarily synthesized and secreted by adipose tissue whose principal action is the control of appetite and energy balance. However, current information suggests that leptin exerts pleiotropic effects on several organ systems. Herein, we review the potential role of leptin in cardiovascular and renal physiological conditions as well as pathophysiological situations including obesity and hypertension.. Increasing evidence suggests that leptin may function as a pressure and volume-regulating factor under conditions of health; however, in situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for adverse renal, vascular and cardiac remodeling.. Adipose tissue should be regarded as a potentially important mediator of cardiorenal physiology. Further research awaits the characterization of additional mechanisms of action of leptin, including its interface with other important endocrine and hemodynamic sodium-volume regulatory systems, in both health and disease, particularly in obesity and related comorbidities. This information could lead to the development of leptin analogues as well as leptin receptor blockers that given specific circumstances could optimize the beneficial actions of the hormone and minimize its deleterious effects.

Topics: Adipose Tissue; Animals; Blood Pressure; Cardiovascular Diseases; Cardiovascular System; Homeostasis; Humans; Hypertension; Kidney; Leptin; Models, Biological; Models, Cardiovascular; Obesity; Receptors, Leptin; Renal Insufficiency, Chronic; Water-Electrolyte Balance

Chronic kidney disease (CKD) patients on hemodialysis may have a modified appetite due to several factors including a lack of uremic toxins elimination. The use of medium cutoff (MCO) dialysis membranes has been suggested as an alternative to improve the removal of toxins, especially those of medium and high molecular weight. This study aimed to compare the effect of hemodialysis using MCO and high-flux membranes on the appetite and leptin levels of CKD patients.. This is a predefined exploratory analysis of a randomized, open study, with a crossover design of 28 weeks of follow-up, which compared the effects of MCO and high-flux membranes in 32 CKD patients on hemodialysis. Appetite assessments were performed using the Appetite and Food Satisfaction Questionnaire.. The MCO group had an appetite score of 3.00 (1.00-5.50) and 3.00 (1.00-5.00) at the beginning and at the end of the treatment period, respectively, while the high-flux group had 1.00 (0.25-6.00) and 2.00 (0.75-3.25). There were no effects of treatment (P = .573), time (P = .376), and interaction (P = .770) between the MCO and high-flux groups. Leptin levels, at the beginning and at the end of the treatment period, were 2,342.30 (1,156.50-4,091.50) and 2,571.50 (1,619.40-4,036.47) pg/mL in the MCO group, respectively, and 2,183.15 (1,550.67-3,656.50) and 2,685.65 (1,458.20-3,981.08) pg/mL in the high-flux group. There was a time effect (P = .014), showing an increase in leptin levels in both groups, while treatment (P = .771) or interaction (P = .218) effects were not observed.. There is no difference between the effects of MCO or high-flux membranes on leptin levels or appetite of CKD patients on hemodialysis.

Topics: Appetite; Humans; Leptin; Renal Dialysis; Renal Insufficiency, Chronic

Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD.. We enrolled patients with moderate to severe CKD through a multi-center pilot randomized trial of diet and exercise in a 4-arm design (dietary restriction of 10%-15% reduction in caloric intake, exercise three times/week, combined diet and exercise, and control) (NCT01150851). Adipocytokines (adiponectin and leptin) were measured at the beginning and end of the study period as secondary outcomes. Treatment effect was analyzed in a multivariable model adjusted for baseline outcome values, age, gender, site and diabetes. A total of 122 participants were consented, 111 were randomized (42% female, 25% diabetic, and 91% hypertensive), 104 started intervention and 92 completed the study (Figure 1). Plasma adiponectin levels increased significantly in response to diet by 23% (95% CI: 0.2%, 49.8%, p = 0.048) among participants randomized to the caloric restriction and usual activity arm but not to exercise, whereas circulating leptin did not change by either treatment.. Our data suggest that dietary caloric restriction increases plasma adiponectin levels in stage 3-4 CKD patients, with limited effect on leptin levels. These findings suggest the potential for improving the metabolic milieu of CKD with moderate calorie restriction.

Topics: Adipokines; Adiponectin; Adult; Aged; Biomarkers; Caloric Restriction; Exercise Therapy; Female; Humans; Leptin; Male; Middle Aged; Physical Endurance; Pilot Projects; Renal Insufficiency, Chronic; Severity of Illness Index; Time Factors; Treatment Outcome; United States

Endothelial dysfunction (ED) has a high incidence in chronic kidney disease (CKD) and is identified as a precursor to cardiovascular events. Recent studies suggest that leptin may be the missing link between ED and CKD. The objective of this study was to investigate the mechanism by which leptin causes ED and the connection with leptin and indicators of ED in CKD patients. Analysis of leptin-treated human umbilical vein endothelial cells (HUVECs) showed increased expression of interleukin 6 (IL-6), endothelin 1 (ET-1) and human monocyte chemoattractant protein 1 (MCP-1), resulting in F-actin recombination and vinculin aggregation as well as endothelial cell migration. In vitro studies have shown that leptin leads to increased WNT1 expression and the accumulation of β-catenin. Metastasis-associated protein 1 (MTA1), a critical upstream modifier of WNT1 signaling, increased the expression level in leptin-mediated regulation. In contrast, opposite results were observed when cells are transfected with MTA1 or WNT1 shRNA lentivirus vectors. Among 160 patients with CKD and 160 healthy subjects, patients with CKD had significantly higher serum leptin levels than those of the control group, which were positively correlated with increased levels of IL-6, ET-1 and MCP-1. However, these levels were negatively correlated with flow-mediated dilatation (FMD). Hence, these investigations provided novel information on the increased serum leptin levels in CKD patients leading to ED via the MTA1-WNT/β-catenin pathway.

Topics: Adult; beta Catenin; Endothelium, Vascular; Female; Human Umbilical Vein Endothelial Cells; Humans; Leptin; Male; Middle Aged; Renal Insufficiency, Chronic; Repressor Proteins; Trans-Activators; Wnt Signaling Pathway

The nature of the link (causal vs non-causal) between low 1,25-OH vitamin D and insulin resistance (IR) in patients with chronic kidney disease (CKD) remains elusive. We have now made a post hoc analysis of the effect of vitamin D receptor activation by paricalcitol on IR in the complete dataset of a double-blind, randomized, placebo controlled trial, the Paricalcitol and ENdothelial fuNction in chronic kidneY disease (PENNY).. Eighty-eight patients with stage 3-4 CKD were randomized (1:1) to receive 2 μg/day paricalcitol or matching placebo for 12 weeks. IR was measured by five IR indices: the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), the McAuley index, the HOMA corrected for adiponectin (HOMA-AD) and the Leptin-adiponectin ratio (LAR). As compared to placebo, paricalcitol produced the expected small rise in serum calcium (+0.07 mmol/L, P = 0.01) and phosphate (+0.08 mmol/L, P = 0.034) and the expected parathyroid hormone suppression (-96 pg/ml, P < 0.001). However, the drug largely failed to affect the five indices of IR which remained unchanged both in the active and the placebo arm (paricalcitol vs placebo, P ranging from 0.25 to 0.62) and no effect modification of paricalcitol on IR by vitamin D or other parameters was registered.. Paricalcitol treatment for 12 weeks does not improve IR in patients with stage 3-4 CKD. Low vitamin D receptor activation is not a causal factor for IR in the CKD population.

Topics: Adiponectin; Aged; Biomarkers; Blood Glucose; Double-Blind Method; Ergocalciferols; Female; Humans; Insulin; Insulin Resistance; Italy; Leptin; Male; Middle Aged; Receptors, Calcitriol; Renal Insufficiency, Chronic; Time Factors; Treatment Outcome

Leptin is an adipokine that regulates various metabolism, but its association with secondary hyperparathyroidism (SHPT), a clinical manifestation of chronic kidney disease-mineral and bone disorder (CKD-MBD), remains obscure. Parathyroidectomy (PTX) is recommended for severe SHPT patients. Here, the associations between circulating leptin and clinical characteristics in CKD patients were investigated. Effects of PTX on leptin production were analyzed in vivo and in vitro. Controls and CKD patients had approximate serum leptin levels in that a larger proportion of CKD patients with body mass index (BMI) <23 kg/m(2). Serum leptin was related to anemia, albumin, and bone metabolism disorders in CKD patients. Lower intact parathyroid hormone (PTH) was related with higher leptin in PTX patients group. Severe SHPT inhibited uremia-enhanced leptin production in 3T3-L1 adipocytes, which was attenuated after PTX. High levels of PTH were found to reduce Akt phosphorylation and leptin production in vitro but high levels of calcium and phosphorus were not. Successful PTX was found to improve anemia and malnutrition in severe SHPT patients, and this was correlated with increased circulating leptin levels via up-regulated Akt signaling in adipocytes. These findings indicated the therapeutic potential of leptin and related target pathway for improving survival and quality of life in CKD.

Topics: Adolescent; Adult; Aged; Anemia; Bone Diseases; Female; Humans; Leptin; Male; Malnutrition; Middle Aged; Parathyroidectomy; Renal Insufficiency, Chronic

The aim of this study was to evaluate the effects of adipocytokines including adiponectin, leptin, resistin, neuropeptide Y and ghrelin in chronic kidney disease (CKD) patients on appearance of protein-energy wasting (PEW). One hundred fifty patients with mean age of 45.4 ± 15.9 years, without active infections or chronic inflammatory conditions were recruited into the study. Study groups were control group (consisting of 30 healthy volunteers with normal kidney functions), hemodialysis group, predialysis group, peritoneal dialysis group and kidney transplant group. Fasting morning serum leptin, ghrelin, acylated ghrelin, neuropeptide Y, adiponectin, resistin levels of all of the groups were measured. Anthropometric and nutritional assessments of all patients were obtained. Diagnosis of PEW was made according to definition recommended by the International Society of Renal Nutrition and Metabolism. Presence of PEW in hemodialysis (23.3%) and peritoneal dialysis (26.7%) groups were significantly higher than those of predialysis (3.3%), and transplantation (0%) groups. Adiponectin and resistin levels in predialysis, peritoneal dialysis and hemodialysis patients were significantly higher than control group (p: 0.0001). This study had given significant positive correlations between presence of PEW and serum resistin (r: 0.267, p: 0.001), and serum adiponectin levels (r: 0.349, p: 0.0001). There were no relationship between presence of PEW and ghrelin, acylated-ghrelin, neuropeptide Y, and leptin levels of the groups. CKD patients except transplant patients had higher adiponectin and resistin levels than control group. PEW was found to be linearly correlated with resistin and adiponectin. High serum resistin and adiponectin levels might have a role in development of PEW among dialysis patients.

Topics: Adiponectin; Adult; Base Sequence; Female; Ghrelin; Humans; Leptin; Male; Molecular Sequence Data; Neuropeptide Y; Nutrition Assessment; Peritoneal Dialysis; Protein Deficiency; Renal Insufficiency, Chronic; Resistin; Wasting Syndrome; Young Adult

Adiponectin, an adipose tissue derived hormone, is known to have insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties in the general population. Adiponectin secretion is suppressed by systemic inflammation, a highly prevalent condition in maintenance hemodialysis (MHD) patients. We evaluated whether short-term administration of interleukin 1 receptor antagonist (IL-1ra) improves adiponectin levels and insulin sensitivity in MHD patients.. Ad hoc analysis was performed on a pilot randomized placebo-controlled trial of the administration of IL-1ra in chronically inflamed MHD patients. Twenty-two patients were randomly assigned to receive 100 mg of IL-1ra or placebo (1:1) for 4 weeks, and 14 completed the trial. ANCOVA was used to compare percent change from baseline to 4 weeks. The primary outcome was percent change in adiponectin and the secondary outcomes were changes in leptin, homeostatic model assessment of insulin resistance (HOMA-IR) and the leptin-to-adiponectin ratio (LAR).. Patients' mean age was 49 ± 13 years, and 71 % were males. At baseline, the median values for adiponectin, leptin, LAR and HOMA-IR were 11.5 μg/ml [interquartile range (IQR) 9, 28.5], 17.8 ng/ml (3.9, 50.0), 2.20 (0.13, 3.98), and 2.8 (2.0, 3.6), respectively. IL-1ra administration resulted in a mean percent increase in serum adiponectin of 22 % vs. 14 % decrease in the placebo arm (p = 0.003). Leptin, LAR or HOMA-IR levels did not change in either arm.. Short-term administration of IL-1ra significantly increased adiponectin levels among prevalent MHD patients. The intervention did not impact insulin sensitivity parameters. Studies of longer duration and larger sample size are needed to further evaluate the potential effect of anti-inflammatory interventions on metabolic markers and insulin sensitivity in MHD patients.

Topics: Adiponectin; Adult; Aged; Anti-Inflammatory Agents; Biomarkers; Female; Humans; Inflammation; Insulin Resistance; Interleukin 1 Receptor Antagonist Protein; Leptin; Male; Middle Aged; Pilot Projects; Renal Dialysis; Renal Insufficiency, Chronic; Tennessee; Time Factors; Treatment Outcome; Up-Regulation

Mineral bone disorder (MBD) is an early complication of chronic kidney disease (CKD), with complex interactions in the bone-kidney-energy axis. These events lead to impaired bone remodelling, which in turn is associated with cardiovascular disease. Recently, we reported on a positive effect of phosphate binder treatment on bone remodelling markers and a reduction in serum FGF-23 levels in predialysis-CKD patients. The goal of the present study of this trial was to examine the effects of phosphate binders on energy-regulating hormones and Wnt pathway.. In this present post hoc analysis of the above randomized, open-label, 8-week trial, which compared the effects of increasing doses of sevelamer-HCl or calcium acetate on various CKD-MBD parameters in 40 normophosphatemic CKD Stage 3-4 patients, we measured serum sclerostin, Dickkopf-1, leptin, adiponectin and serotonin concentrations.. Serum sclerostin, Dickkopf-1 and leptin were elevated at baseline despite normal calcium, phosphorus levels and daily urinary phosphorus excretion. There were significant and positive correlations between sclerostin and FGF-23, as well between leptin and Dickkopf-1. Treatment with both phosphate binders led to a significant decrease in phosphate overload. However, sevelamer-HCl, but not with calcium acetate, led to a significant decrease in serum FGF-23, sclerostin and leptin, and to a significant increase in bone alkaline phosphatase levels.. Early stages of CKD are associated with an impairment of the Wnt pathway, as reflected by elevated sclerostin, and a dysregulation of energy-regulating hormones. Many of these disturbances can be ameliorated by phosphate binder treatment, more with sevelamer-HCl than with calcium acetate.

Topics: Acetates; Adaptor Proteins, Signal Transducing; Adiponectin; beta Catenin; Biomarkers; Bone Density; Bone Diseases; Bone Morphogenetic Proteins; Calcium Compounds; Chelating Agents; Energy Metabolism; Female; Fibroblast Growth Factor-23; Genetic Markers; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Polyamines; Renal Insufficiency, Chronic; Serotonin; Sevelamer; Wnt Proteins

Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD). Previous studies argued that leptin levels increase significantly with the progression of CKD. But the association between leptin and CKD has not been investigated in patients with NAFLD. Therefore, we conducted this study to establish whether increased leptin level is associated with CKD in NAFLD patients.. In our prospective study with a follow up period of six months thirty-five teetotaller biopsy-proven NAFLD patients were divided as groups with mild, versus advanced, fibrosis. Liver fibrosis was also assessed with Fibroscan. Serum leptin levels were measured by radioimmunoassay. For insulin resistance we used the homeostasis model assessment method (HOMA-IR). For the kidney function, we used the abbreviated formula Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR. For statistical analysis, Student's-t test, Mann-Whitney test, linear regression-binary logistic regression analyses and the ROC curve analysis were used.. Advanced fibrosis and increased HOMA-IR were risk factors for decreased eGFR. Leptin correlated inversely with advanced fibrosis (p: 0.03) and low leptin was a risk factor for CKD (p: 0.02). In ROC curve analysis, advanced fibrosis and low leptin were risk factors for decreased eGFR (p: 0.007 and 0.004, respectively). Low leptin level was dependently associated with decreased eGFR.. Advanced fibrosis in NAFLD patients is a risk factor for CKD. Leptin correlated inversely with advanced fibrosis. Unlike the previous studies, which were not performed in NAFLD patients, we found decreased leptin in NAFLD patients with decreased eGFR. Low leptin level was found to be a dependent predictor for differentiating NAFLD patients with high risk for CKD.

Topics: Humans; Kidney; Leptin; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Prospective Studies; Renal Insufficiency, Chronic

Adipokines are associated with cardiovascular disease; in chronic kidney disease (CKD) patients adipokines could be useful prognostic factors.. To explore whether leptin and adiponectin in kidney replacement therapy (KRT) children could have a role on their cardiac function, in the long-term.. Prospective cohort study was performed with pediatric KRT patients, aged 8 to 17 years who were undergoing hemodialysis or peritoneal dialysis. At enrollment, lipid profile, adipokines (leptin, leptin receptor, free leptin, and adiponectin), anthropometric measurements and cardiological evaluation were determined. At two-year follow-up, a new cardiological evaluation was performed.. We included 56 patients, with a median age of 12.5 years. In the first cardiological evaluation, median LVEF was 70.0% (IQR 61%, 76%), 20 patients (35.7%) had some cardiovascular condition, and 10 (17.8%) altered LVEF. At 24-month follow-up, the median LVEF was 70.5% (IQR 65.1%, 77%), while the delta-LVEF values was 3% (IQR -6.5%, 7%). Delta-LVEF were correlated with baseline adipokines serum levels, and the only positive correlation found was with free leptin (r=0.303, p=0.025). In multivariate analysis, levels of free leptin (Coef. 0.12, p<0.036) and leptin (coef. 1.72, p=0.049), as well as baseline LVEF (Coef. -0.65, p<0.001) were associated with delta-LVEF.. Free leptin, leptin and LVEF at the beginning of follow-up were associated with the LVEF decrease at the 24-month follow-up in KRT children.

Topics: Adipokines; Adiponectin; Cardiovascular Diseases; Child; Humans; Leptin; Prospective Studies; Renal Insufficiency, Chronic

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

The prevalence of obesity and chronic kidney disease (CKD) is increasing simultaneously and rapidly worldwide. Our previous study showed that folate deficiency increased lipid accumulation and leptin production of adipocytes. Whether folate plays a role in CKD, particularly obesity-related nephropathy remains unclear. To investigate the effects of folate deficiency on CKD in diet-induced obese mice, four groups of male C57BL/6 mice were fed either a normal-fat diet (NF) with folate (NF+f); NF without folate (NF-f); high-fat high-fructose diet (HFF) with folate (HFF+f); or HFF without folate (HFF-f) for 12 months during the study. The results showed that HFF increased not only body weight, fasting blood glucose, total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and blood pressure, but also cytokines levels, such as interleukin (IL)-2, interferon (IFN)-γ, IL-17A/F, IL-6, monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-β1. The indicators of kidney failure including urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), renal type I and IV collagen deposits and leptin content, and serum creatinine were also increased by HFF. Folate-deficient diets further elevated serum TC, LDL-cholesterol, IL-6, tumor necrosis factor (TNF)-α, MCP-1, TGF-β1, and leptin, but decreased IL-10 level, and thus exacerbated renal fibrosis. To investigate the possible mechanisms of folate deficiency on renal injury, phosphorylation of pro-fibrosis signaling molecules, including signal transducer and activator of transcription (STAT)3 and small mothers against decapentaplegic (Smad)2/3, were assayed. Both HFF and folate deficiency significantly increased the phosphorylation of STAT3 and Smad2/3, suggesting synergistic effects of HFF-f on chronic renal inflammation and fibrosis. In conclusion, the results demonstrated that folate deficiency might aggravate inflammatory status and enhance renal fibrosis.

Topics: Animals; Folic Acid; Folic Acid Deficiency; Inflammation; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Renal Insufficiency, Chronic

Chronic kidney disease(CKD) is a major public health issue and is highly prevalent in the general population. Leptin is an adipose tissue-derived endocrine factor that has been associated with several metabolic factors involved in cardiovascular diseases. Several studies have investigated the association between leptin and renal diseases so far. But the results are conflicting between the studies. The objective of our study was to verify the direct association of serum leptin level with CKD development.. This prospective cohort study included 2646 adult aged 40-70 without CKD in the Korean Genome and Epidemiology Study(KoGES) across South Korea from November 2005 to February 2012. The primary outcome was the development of CKD as defined by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI). Multivariate stepwise logistic regression analysis was done to assess the independent associations, for with the incident of CKD as the dependent variable, in tertiles of leptin values.. Among 1100 men and 1546 women with 2.8 mean years of follow-up, incidence of CKD was 18(1.63%) for men and 50(3.23%) for women. In the multivariate logistic regression models, individuals in the highest serum leptin tertile showed significant associations with risk of CKD after adjustment compared to the lowest tertiles in the population. The crude odds ratio for trend was 2.95(p = 0.004) for men. After adjusting for age, baseline eGFR variables showed correlation with statistical significance (OR for trend = 2.25, p = 0.037) for men. The same trends were also seen observed in all population and women also, but no statistical significance was found.. Higher plasma leptin levels are associated with the incidence of CKD, independent of traditional factors such as age, baseline eGFR. Our results suggest that leptin may partly explain part of the reported association between obesity and kidney disease.

Topics: Adult; Female; Humans; Incidence; Leptin; Longitudinal Studies; Male; Prospective Studies; Renal Insufficiency, Chronic

An imbalance in adipokines is associated with the progression of chronic kidney disease (CKD) in humans. However, alterations in adipokines in dogs with CKD remain unclear.. To examine whether adipokine concentrations in serum differ between healthy dogs and dogs with CKD and to determine the correlation between serum adipokine concentrations and CKD severity in dogs.. Twenty dogs with CKD and 10 healthy dogs.. In this cross-sectional study, serum concentrations of leptin, adiponectin, interleukin (IL)-6, IL-10, IL-18, and tumor necrosis factor (TNF)-α were measured in healthy dogs and dogs with CKD, which were classified according to the International Renal Interest Society guidelines.. Serum leptin concentrations were positively correlated with systolic arterial blood pressure (r = .41), creatinine concentrations (r = .39), and symmetric dimethylarginine concentrations (r = .73). Serum adiponectin concentrations (median [range]) in CKD dogs with borderline or non-proteinuric (20.25 [14.9-45.8] ng/mL) were significantly higher than those in proteinuric CKD dogs (13.95 [6.4-22.1] ng/mL; P = .01). Serum IL-6 (median [range]; 43.27 [24.30-537.30] vs 25.63 [6.83-61.03] pg/mL; P = .02), IL-18 (median [range]; 25.98 [11.52-280.55] vs 10.77 [3.53-38.45] pg/mL; P = .01), and TNF-α (median [range]) concentrations (11.44 [8.54-38.45] vs 6.105 [3.97-30.68] pg/mL; P = .02) were significantly different between proteinuric and borderline or non-proteinuric CKD dogs.. leptin and adiponectin concentrations in serum might be associated with severity of CKD and proteinuria in dogs with CKD, respectively.

Topics: Adipokines; Adiponectin; Animals; Cross-Sectional Studies; Dog Diseases; Dogs; Interleukin-18; Interleukin-6; Leptin; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

Background: leptin and adiponectin are associated with cardiovascular disease in chronic kidney disease (CKD) patients and could be useful prognostic factors. Objectives. to explore the usefulness of the leptin/adiponectin ratio (LAR) to predict the presence or worsening of dyslipidemia during 1 year of follow-up in children receiving kidney replacement therapy (KRT). Material and methods: a prospective cohort study was performed. Pediatric KRT patients aged between 8 and 17 years who were undergoing hemodialysis or peritoneal dialysis were included. At enrollment, the lipid profile, adiponectin and leptin levels, and somatometric measurements, including body fat percentage, were determined. At the one-year follow-up, the lipid profile was reassessed. Results: of the 70 patients included, the median age was 13 years, and there was no sex predominance (52.8 % males). At the end of follow-up, the patients were divided into three groups: those without dyslipidemia (WOD), those who developed or experienced worsening of their dyslipidemia (DWD) and those with persistent dyslipidemia (PD). A LAR > 0.85 (OR, 16.7) and body fat percentage (OR, 1.46) were associated with an increased risk of PD and DWD at 12 months, independently of urea level, BMI Z-score, benzafibrate treatment, CKD progression time, and replacement treatment. Conclusions: a LAR > 0.85 and fat body percentage at the beginning of follow-up were strongly associated with the presence, persistence or worsening of dyslipidemia at the 12-month follow-up in children with KRT.. Antecedentes: la leptina y la adiponectina se asocian con enfermedad cardiovascular en los pacientes con enfermedad renal crónica (ERC) y podrían ser factores pronósticos útiles. Objetivos: explorar la utilidad del cociente leptina/adiponectina (LAR) para predecir la presencia o empeoramiento de la dislipidemia durante 1 año de seguimiento en niños que reciben terapia de reemplazo renal (TRR). Material y métodos: se realizó un estudio de cohortes prospectivo. Se incluyeron pacientes pediátricos con TRR de entre 8 y 17 años que estaban en hemodiálisis o diálisis peritoneal. Al inicio del estudio se determinaron el perfil lipídico, los niveles de adiponectina y leptina, y las mediciones somatométricas, incluido el porcentaje de grasa corporal. En el seguimiento de un año, se reevaluó el perfil de lípidos. Resultados: de los 70 pacientes incluidos, la mediana de edad fue de 13 años y no hubo predominio de sexo (52,8 % de varones). Al final del seguimiento, los pacientes se dividieron en tres grupos: aquellos sin dislipidemia (SD), aquellos que desarrollaron o experimentaron un empeoramiento de su dislipidemia (ED) y aquellos con dislipidemia persistente (PD). Un LAR > 0,85 (OR: 16,7) y el porcentaje de grasa corporal (OR: 1,46) se asociaron con un mayor riesgo de ED y PD a los 12 meses, independientemente del nivel de urea, la puntuación Z del IMC, el tratamiento con benzafibrato, el tiempo de progresión de la ERC y el tratamiento de reemplazo. Conclusiones: un LAR > 0,85 y el porcentaje de grasa corporal al inicio del seguimiento se asociaron fuertemente con la presencia, persistencia o empeoramiento de la dislipidemia a los 12 meses de seguimiento en niños con TRR.

Topics: Adiponectin; Adolescent; Child; Dyslipidemias; Female; Follow-Up Studies; Humans; Leptin; Lipids; Male; Peritoneal Dialysis; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Urea

Knowledge of chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys is limited as few studies have explored this disorder. This study aimed to identify the usefulness of assessing hormonal parameters in male adolescents with CKD and their correlation with PD in a 12-month follow-up period.. A prospective cohort study was conducted among male adolescents with CKD (stages IV and V). Data regarding the age at puberty onset were collected from the patients' clinical records and through interview. The patients were followed up for 12 months during their pubertal development. At the beginning, routine hormonal profile tests were performed to examine the patients' thyroid profile, prolactin levels, luteinizing hormone, follicle-stimulating hormone, testosterone, leptin, and receptor leptin. The hormonal profiles of patients with and without PD were compared. Comparisons between the groups were performed using the Student t-test and Fisher's exact tests. Logistic regression analysis was also performed.. Data of 64 patients (26/64 with PD) were analyzed. The median age was 15 years and the median time for CKD evolution was 11 months. No differences between groups were noted in the general or biochemical characteristics of the patients. The hormonal parameters, prolactin levels were higher and the free leptin and free thyroxine levels were lower in patients with PD. Leptin receptor levels of >0.90 ng/mL (risk ratio [RR], 8.6; P = 0.004) and hyperprolactinemia (RR, 21.3; P = 0.049) were the risk factors for PD.. Leptin receptor levels of >0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.

Topics: Adolescent; Humans; Hyperprolactinemia; Leptin; Male; Prolactin; Prospective Studies; Puberty; Receptors, Leptin; Renal Insufficiency, Chronic

Plasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail.. The 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson's correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia.. In our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia.. According to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.

Topics: Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hypertension; Kidney; Leptin; Male; Middle Aged; Renal Insufficiency, Chronic; Taiwan; Uric Acid

Leptin potentially exerts atherogenic effects.This study evaluated the relationship between serum leptin levels and aortic stiffness in patients with stage 3-5 chronic kidney disease (CKD). Totally 205 participants were enrolled. Fasting blood sample were checked and serum leptin were measured by enzyme immunoassay. Aortic stiffness was measured as the carotid-femoral pulse wave velocity (cfPWV). 73 (35.6%) of 205 patients showed cfPWV >10 m/s were defined as aortic stiffness group. Compared with the remaining patients, the aortic stiffness group had high prevalence of diabetes mellitus, older age, higher waist circumference, body fat mass, systolic blood pressure, fasting glucose, and higher serum leptin level. In multivariable logistic regression analysis the independent predictors of cfPWV >10 m/s included leptin levels (odds ratio [OR]: 1.061, 95% confidence interval [CI]: 1.027-1.095, 

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Comorbidity; Disease Susceptibility; Female; Humans; Kidney Function Tests; Leptin; Male; Middle Aged; Odds Ratio; Pulse Wave Analysis; Renal Insufficiency, Chronic; Severity of Illness Index; Vascular Stiffness

Chronic kidney disease adversely affects the structure and metabolism of bone tissue, which may be a result of disturbed biochemical processes in adipose tissue. Renal replacement therapy is a life-saving therapy but it does not restore all metabolic functions and sometimes even escalates some disturbances. The study included 126 subjects: 47 hemodialysis patients (HD), 56 patients after renal transplantation (Tx) and 23 healthy controls (K). Bone density at the femoral neck (FN) and lumbar spine (LS), as well as body composition (adipose tissue content and lean body mass) were measured in each patient using the DXA method. In addition, serum concentrations of glucose, calcium, phosphorus, parathormone, FGF23, Klotho, osteocalcin, leptin, adiponectin and 1,25-dihydroxyvitamin D3 were measured. We observed significantly higher concentrations of leptin, FGF23 and Klotho proteins in the HD patients (77.2±48.1 ng/ml, 54.7±12.4 pg/ml, 420.6±303.8 ng/ml, respectively) and the Tx group (33.2±26.5 ng/ml; 179.8±383.9 pg/ml; 585.4±565.7, respectively) compared to the control group (24.4±24.6 ng/ml, 43.3±37.3 pg/ml, 280.5±376.0 ng/ml). Significantly lower bone density at FN was observed in the HD and Tx patients in comparison to the controls and in the HD patients compared to the Tx group. There were no significant differences in body mass composition between the studied groups. The results of this study indicate that both hemodialysis and transplantation are associated with increased serum concentrations of leptin, FGF23 and Klotho proteins, as well as lower bone density at femoral neck.

Topics: Adult; Aged; Bone Density; Bone Remodeling; Female; Femur Neck; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Kidney Transplantation; Klotho Proteins; Leptin; Lumbar Vertebrae; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic

To investigate the nutritional status of children on maintenance hemodialysis due to stage 5 chronic kidney disease (CKD) and the clinical significance of nutritional assessment indices.. A total of 21 children on maintenance hemodialysis due to stage 5 CKD were grouped according to body mass index. The nutritional status was assessed based on anthropometric parameters, biochemical parameters, inflammatory factors, residual renal function, indices of dialysis adequacy, and resting energy expenditure. Related indices were compared between the children with malnutrition and those with normal nutritional status.. Of the 21 children, 10 had malnutrition and 11 had normal nutritional status. There were significant differences between the two groups in anthropometric parameters, levels of leptin, insulin-like growth factor-1, interleukin-1, interleukin-6, and tumor necrosis factor-α, and mean 24-hour residual urine volume (P<0.05), while there were no significant differences in albumin, prealbumin, CONCLUSIONS: urea clearance index (Kt/V), and measured resting energy expenditure.. Anthropometric parameters, biochemical parameters, residual renal function, and inflammatory factors have an important value in evaluating the nutritional status of children with stage 5 CKD on maintenance hemodialysis. Further studies are needed to investigate the value of the measurement of resting energy expenditure in the evaluation and monitoring of nutritional status in children with stage 5 CKD on maintenance hemodialysis.

Topics: Adolescent; Child; Energy Metabolism; Female; Humans; Interleukin-6; Leptin; Male; Nutritional Status; Renal Dialysis; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

Fibroblast growth factor 23 (FGF-23) may be involved in signaling between bone and adipose tissue in dialysis patients, but its role is uncertain. We sought to examine the association between FGF-23 and adiposity and whether this association is mediated in part by leptin.. We performed univariate and multivariate linear regression analyses using data from 611 participants in a cohort of prevalent hemodialysis patients recruited from dialysis centers in Atlanta, GA and San Francisco, CA from 2009 to 2011. We also investigated the role of leptin in these relationships.. Participants were aged ≥18 years, English or Spanish speaking, and receiving hemodialysis for at least 3 months.. Outcome measures of adiposity included body mass index, waist circumference, and body fat measured by bioelectrical impedance spectroscopy.. Mean age was 56 ± 14 years, 39.8% were female, and median serum FGF-23 was 807 pg/mL. In fully adjusted models, FGF-23 was inversely associated with body mass index (-0.24 kg/m. We found a negative association between FGF-23 and adiposity that appears to be mediated in part by leptin. As adipose tissue provides a "protective energy depot" for patients with chronic illness, a decrease in adipose tissue may be one mechanism in which higher FGF-23 levels may contribute to increased mortality in dialysis patients.

Topics: Adipose Tissue; Adiposity; Body Mass Index; Cohort Studies; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Leptin; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Waist Circumference

Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular complications and plasma leptin level is elevated in cardio renal syndrome. We wanted to explore leptin levels in patients with different stages of CKD and find its association with risk of cardiovascular disease. This cross-sectional study was conducted in Nephrology Department of Jinnah Post Graduate Medical Centre (JPMC) from January 2014 to September 2014. Group I comprised of controls (GFR=116±8.3, n = 44) acquired from general population, CKD patients were grouped as II, III and IV respectively with GFR; 85.77±9.9 (n = 42), 53.84±9.9 (n=42) and 20.22±8.4 (n = 42).CKD patients with any inflammatory disease, Diabetes Mellitus and on steroid therapy were excluded. Serum leptin, lipid profile and C reactive proteins (CRP) were measured. Leptin and CRP levels increased significantly with progression of CKD. High density lipoproteins (HDL) to low density lipoproteins (LDL) ratio was significantly high in control as compared to CKD groups (p<0.001). A positive correlation of leptin was observed with CRP and HDL/LDL ratio (r= 0.994,p<0.001 and r=-0.403 p<0.001) respectively. Hyperleptinemia observed with progression of CKD contributed to pathogenesis of cardiovascular disease by decreasing HDL/LDL ratio.

Topics: Adult; Biomarkers; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Leptin; Male; Middle Aged; Renal Insufficiency, Chronic

This study aimed to evaluate plasma concentrations of leptin and total ghrelin in children with chronic kidney disease (CKD) and assess their roles in protein-energy wasting (PEW).. This study consisted of three different CKD populations [CKD group (20 patients with non-dialysis CKD), dialysis group (39 patients on dialysis), and kidney transplant (KTx) group (35 KTx recipients)] and control group (18 healthy children). Plasma leptin and total ghrelin levels were measured. Multi-frequency bioimpedance analysis was used for the assessment of fat and lean mass. PEW was defined using criteria including body mass, muscle mass, growth, serum albumin level, and protein intake.. While plasma leptin levels did not differ among the study groups, total ghrelin levels were significantly higher in the dialysis group (P < 0.001). Seven dialysis patients (18%) and one CKD patient (5%) but none of the KTx recipients met the criteria of PEW. Dialysis patients with PEW had lower plasma leptin levels compared to their counterparts (P = 0.018); however, total ghrelin levels did not differ between the two groups (P = 0.10). Low leptin level in dialysis patients was independently associated with lower fat mass index (P < 0.001) and lower height-specific SD scores of BMI (P = 0.019).. PEW is prevalent in dialysis patients. Low levels of leptin seem to be associated with PEW. Our result suggests that low leptin levels may be a consequence rather than a cause of PEW. Longitudinal studies are required to investigate this complex relationship between leptin and PEW in pediatric dialysis patients.

Topics: Adolescent; Body Fat Distribution; Body Mass Index; Child; Female; Ghrelin; Humans; Kidney Transplantation; Leptin; Male; Prevalence; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency, Chronic

Patients with early-stage chronic kidney disease (CKD) are susceptible to changes in metabolic processes. Partial loss of kidney function leads to homoeostatic disturbances in bone and fatty tissue. The aim of this study was to investigate the association between plasma concentrations of Klotho protein, FGF23, leptin, adiponectin, osteocalcin, and bone mineral density (BMD) in patients with CKD in the pre-dialysis period. The study involved 52 patients with CKD and 23 patients with no kidney disease. In both groups, BMD, body mass index and serum or plasma concentrations of lipids, glucose, creatinine, calcium, phosphorus, parathormone, leptin, adiponectin, osteocalcin, Klotho, and FGF23 were measured. The group with CKD had statistically significant higher concentrations of leptin (p<0.001), parathormone (p<0.001), and osteocalcin (p<0.001) in comparison with the control group. Patients with CKD also had statistically significant lower BMD in the femoral neck in comparison with the control group. Osteocalcin correlated negatively with BMD. The results of our study suggest that elevated osteocalcin is the most sensitive marker of decreased bone mass in patients with CKD. Osteocalcin correlated negatively with BMD and GFR. The loss of bone mass in CKD patients was greatest in the femoral neck.

Topics: Adiponectin; Adult; Aged; Bone Density; Case-Control Studies; Female; Femur Neck; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glucuronidase; Humans; Klotho Proteins; Leptin; Male; Middle Aged; Osteocalcin; Renal Insufficiency, Chronic

Hypogonadism is a common endocrine disorder in men with chronic kidney disease (CKD), but its pathophysiology is poorly understood. We here explore the plausible contribution of abdominal adiposity and leptin hyperproduction to testosterone deficiency in this patient population.. Cross-sectional analysis with all men included the Malnutrition, Inflammation and Vascular Calcification cohort, which enrolled consecutive nondialyzed patients with CKD stages 3-5.. A total of 172 men with CKD stages 3-5 nondialysis (median age 61 [45-75] years, median glomerular filtration rate 24 [9-45] mL/min/1.73 m. None, observational study.. Total testosterone, hypogonadism.. The median level of total testosterone was 11.7 (7.3-18.4) nmol/L, with hypogonadism (<10 nmol/L) present in 52 (30%) patients. Testosterone-deficient patients presented with significantly higher body mass index, waist circumference, and VAT. An inverse correlation between testosterone and VAT (rho = -0.25, P = .001) or waist circumference (rho = -0.20, P = .008) was found, also after multivariate adjustment including sex hormone binding globulin and estrogen. Total testosterone was inversely correlated with serum leptin (rho = -0.22, P = .003), and the ratio of leptin/VAT, an index of leptin hyperproduction, was strongly and independently associated with the prevalence of hypogonadism in multivariable regression analyses.. Visceral adiposity independently associated with lower testosterone levels among men with CKD stage 3-5 nondialysis. The observed link between hyperleptinemia and hypogonadism is in line with previous evidence on direct effects of leptin on testosterone production.

Topics: Adiposity; Aged; Body Mass Index; C-Reactive Protein; Cholesterol; Cross-Sectional Studies; Estrogens; Glomerular Filtration Rate; Hand Strength; Humans; Hypogonadism; Intra-Abdominal Fat; Leptin; Logistic Models; Male; Middle Aged; Prevalence; Renal Insufficiency, Chronic; Sex Hormone-Binding Globulin; Testosterone; Waist Circumference

The negative relation of serum adiponectin to atherosclerosis becomes a positive association in patients with chronic kidney disease (CKD). We conducted a small-scale cross-sectional observational study, in 101 Japanese male hemodialysis patients, to examine the relationship of serum adiponectin and leptin to abdominal aortic calcification (AAC). The presence of AAC was evaluated from simple X-ray radiographs of the left lateral abdomen. Serum adiponectin was significantly higher in AAC-positive patients [18.8 (13.0-28.1) μg/mL] than in AAC-negative patients [15.4 (8.9-22.8) μg/mL] (p = 0.03), whereas serum leptin did not differ significantly between the two groups. Multiple logistic regression analysis showed that log adiponectin, but not log leptin, was independently and significantly associated in a positive manner with AAC (odds ratio: 16.31, 95% confidence interval: 1.70-156.41, p = 0.02), after adjustment for age, body weight, percentage body fat, hemodialysis duration, prevalence of diabetes mellitus, and other risk factors. In conclusion, we found a positive and independent association of serum adiponectin with AAC in male hemodialysis patients, indicating that the reversed association between serum adiponectin and atherosclerosis in patients with CKD dose not result from increased serum adiponectin due to the impaired urinary secretion.

Topics: Adiponectin; Aged; Aorta, Abdominal; Asian People; Cross-Sectional Studies; Humans; Leptin; Logistic Models; Male; Middle Aged; Radiography; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification

Chronic kidney disease (CKD) results in decreased bone strength. Serotonin (5-HT) is one of the critical regulators of bone health, fulfilling distinct functions depending on its synthesis site: brain-derived serotonin (BDS) favors osteoblast proliferation, whereas gut-derived serotonin (GDS) inhibits it. We assessed the role of BDS and peripheral leptin in the regulation of bone metabolism and strength in young rats with 5/6 nephrectomy. BDS synthesis was accelerated during CKD progression. Decreased peripheral leptin in CKD rats was inversely related to BDS content in the hypothalamus, brainstem and frontal cortex. Serotonin in these brain regions affected bone strength and metabolism in the studied animals. The direct effect of circulating leptin on bone was not shown in uremia. At the molecular level, there was an inverse association between elevated GDS and the expression of cAMP responsive element-binding protein (Creb) gene in bone of CKD animals. In contrast, increased expression of activating transcription factor 4 (Atf4) was shown, which was associated with GDS-dependent transcription factor 1 (Foxo1), clock gene - Cry-1, cell cycle genes: c-Myc, cyclins, and osteoblast differentiation genes. These results identified a previously unknown molecular pathway, by which elevated GDS can shift in Foxo1 target genes from Creb to Atf4-dependent response, disrupting the leptin-BDS - dependent gene pathway in the bone of uremic rats. Thus, in the condition of CKD the effect of BDS and GDS on bone metabolism and strength can't be distinguished.

Topics: Alkaline Phosphatase; Animals; Biomarkers; Biomechanical Phenomena; Bone and Bones; Bone Remodeling; Brain; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Femur; Gastrointestinal Tract; Leptin; Male; Rats, Wistar; Renal Insufficiency, Chronic; Serotonin; Signal Transduction; Vanilmandelic Acid; X-Ray Microtomography

Inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia but why uremia up-regulates pro-inflammatory cytokines is unknown. Toll-like receptors (TLRs) regulate locally the innate immune responses, but it is unknown whether in chronic kidney disease (CKD) TLR4 muscle signalling is altered. The aim of the study is to investigate whether in CKD muscle, TLRs had abnormal function and may be involved in transcription of pro-inflammatory cytokine.. TLR4, phospho-p65, phospho-ikBα, tumour necrosis factor (TNF)-α, phospho p38, Murf 1, and atrogin were studied in skeletal muscle from nondiabetic CKD stage 5 patients (n = 29) and controls (n = 14) by immunohistochemistry, western blot, and RT-PCR. Muscle cell cultures (C2C12) exposed to uremic serum were employed to study TLR4 expression (western blot and RT-PCR) and TLR-driven signalling. TLR4 signalling was abrogated by a small molecule chemical inhibitor or TLR4 siRNA. Phospho AKT and phospho p38 were evaluated by western blot.. CKD subjects had elevated TLR4 gene and protein expression. Also expression of NFkB, p38 MAPK and the NFkB-regulated gene TNF-α was increased. At multivariate analysis, TLR4 protein content was predicted by eGFR and Subjective Global Assessment, suggesting that the progressive decline in renal function and wasting mediate TLR4 activation. In C2C12, uremic serum increased TLR4 as well as TNF-α and down-regulated pAkt. These effects were prevented by blockade of TLR4.. CKD promotes muscle inflammation through an up-regulation of TLR4, which may activate downward inflammatory signals such as TNF-α and NFkB-regulated genes.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Animals; C-Reactive Protein; Cell Line; Cytokines; Female; Humans; Inflammation; Leptin; Male; Mice; Middle Aged; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Rectus Abdominis; Renal Insufficiency, Chronic; Resistin; Signal Transduction; Toll-Like Receptor 4; Transcription Factor RelA; Uremia

Topics: Asian People; Female; Homocysteine; Humans; Leptin; Male; Renal Insufficiency, Chronic

Chronic kidney disease (CKD) leading to kidney failure and end stage renal disease (ESRD) is a common health problem associated with wasting syndrome characterized by inadequate nutrient intake and decrease tissue anabolism and/or catabolism. In CKD adipokines, especially leptin and adiponectin (ADPN), accumulate in serum due to reduced renal clearance. Although, rapidly growing, knowledge of adipocytokines is limited and much is still unknown of the altered adipocytokine pattern in patients with impaired renal function. The aim of this study is to assess the adipocytokines, leptin, and adiponectin in relation to weight loss in pediatric patients with CKD stage-5 treated conservatively (CT) or undergoing maintenance hemodialysis (MHD).. 41 CKD stage-5 patients and 20 healthy controls were included in this study. Serum levels of leptin and adiponectin were determined by ELISA. Leptin gene expression was analyzed using quantitative real time-polymerase chain reactions (QPCR).. Patients had significantly elevated ADPN levels and non significantly elevated serum leptin levels as compared to controls (p < 0.001, p = 0.354, respectively). Leptin gene expression and body mass index (BMI) were highly significantly reduced in CKD stage-5 compared to controls (p < 0.001 for each). There were no significant differences between patients treated conservatively and those undergoing MHD with respect to all studied parameters. Finally, univariate logistic regression analysis revealed no association between leptin, ADPN, and weight loss in CKD stage-5 patients.. The present study showed non significantly elevated or even normalized serum leptin levels, elevated serum adiponectin level and reduced leptin gene expression in CKD stage-5 patients as compared to healthy controls. Patients had significantly lower weight than healthy controls but there was no association between leptin, adiponectin, and weight loss in CKD stage-5 studied patients so, further studies are needed to clarify the role of the two adipokines in body weight loss in those patients.

Topics: Adipokines; Adiponectin; Adolescent; Age Factors; Biomarkers; Body Mass Index; Case-Control Studies; Child; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Logistic Models; Male; Nutritional Status; Predictive Value of Tests; Real-Time Polymerase Chain Reaction; Renal Dialysis; Renal Insufficiency, Chronic; Severity of Illness Index; Treatment Outcome; Weight Loss

Endothelial dysfunction (ED) is a well-recognized instigator of cardiovascular diseases and develops in chronic kidney disease (CKD) with high rate. Recent studies have implicated that leptin is associated with endothelial dysfunction. We investigated the relationship between leptin and markers of ED in CKD patients and how leptin contributed to endothelial damage. 140 CKD patients and 140 healthy subjects were studied. Serum leptin levels were significantly higher in CKD than in controls and displayed significantly positive association with the increase levels of sICAM-1 and sVCAM-1 but negative correlation with flow-mediated dilatation (FMD) reduction in patients. Our in vitro study demonstrated that leptin induced overexpression of ICAM-1 and VCAM-1, led to f-actin reorganization and vinculin assembly, increased endothelial monolayer permeability for FITC-dextran, and accelerated endothelial cell migration; these changes were markedly reversed when the cells were transfected with AKT or β-catenin shRNA vectors. Notably, high leptin resulted in hyper-phosphorylation of AKT and GSK3β, along with nuclear accumulation of β-catenin. In conclusion, serum leptin was elevated in CKD patients and it might contribute to endothelial dysfunction by disarrangement of f-actin cytoskeleton via a mechanism involving the AKT/GSK3β and β-catenin pathway.

Topics: beta Catenin; Endothelium, Vascular; Female; Glycogen Synthase Kinase 3 beta; Humans; Leptin; Male; Middle Aged; Proto-Oncogene Proteins c-akt; Renal Insufficiency, Chronic; Signal Transduction; Vascular Resistance

Protein-energy wasting (PEW) contributes to mortality in hemodialysis (HD) patients. Adipokines regulate energy homeostasis and body weight. Circulating gelsolin can modulate inflammation and is correlated with HD mortality. Whether adipokines and gelsolin play important roles in PEW remains unclear. Based on the criteria proposed by the International Society of Renal Nutrition and Metabolism, we examined the associations between PEW and biomarkers (gelsolin, leptin, adiponectin, interleukin-6, tumor necrosis factor alpha [TNF-α]) in 188 stable HD patients. Patients with PEW had significantly lower serum leptin levels, and tended to have higher adiponectin, TNF-α, and lower gelsolin levels. Logistic regression analysis revealed that gelsolin, leptin, adiponectin, and blood urea nitrogen were independently associated with PEW score. Serum creatinine, TNF-α, gender, renin-angiotensin system (RAS) blockade, and lipid-lowering agents were not associated with PEW score. Patients on lipid-lowering agents had lower PEW scores and those with RAS blockade had higher PEW scores. Our study confirms that gelsolin, adiponectin, and leptin are significant associates with PEW in HD patients. Further understanding of how these factors contribute to PEW may help design novel therapeutic strategies for PEW in chronic kidney disease.

Topics: Adipokines; Aged; Biomarkers; Female; Gelsolin; Humans; Interleukin-6; Leptin; Male; Middle Aged; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha

Higher levels of leptin and homocysteine (Hcy) have been evaluated as risk factors of chronic kidney disease in patients and general population. The aim of this study was to examine gender differences in the associations of leptin and Hcy levels and renal function a representative healthy young population in Taiwan.. The participants aged ≥18 years who underwent health examinations were included and categorized into three groups by gender-specific tertiles of leptin and Hcy levels. Estimated glomerular filtration rates (eGFR) were estimated according to the modified equation of Modification of Diet in Renal Disease (MDRD).. A higher mean Hcy level was found in male subjects than females. Mean values of metabolic syndrome risk factors significantly elevated with increasing leptin levels in both genders. Both male and female subjects with higher plasma Hcy levels were more likely to have a lower eGFR. Plasma Hcy levels were significantly negatively correlated with eGFR in linear regression models adjusted for age and smoking. The associations persisted even after mean arterial pressure and fasting plasma glucose were included for adjustments both genders. Plasma Hcy level was negatively associated eGFR and the association was more profound for females.. Leptin levels did not reveal strong or consistent evidence to support a significant association with eGFR. Hcy had a more decisive effect on renal function impairment than leptin and may be considered a more sensitive biomarker for Taiwanese adults.

Topics: Adult; Asian People; Body Mass Index; Creatinine; Cross-Sectional Studies; Female; Glomerular Filtration Rate; Homocysteine; Humans; Leptin; Linear Models; Male; Metabolic Syndrome; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Sex Factors; Smoking; Taiwan

Topics: Female; Humans; Leptin; Male; Renal Insufficiency, Chronic

Adiponectin and leptin, two of the key cytokines secreted by adipocytes, have been shown to be associated with cardiovascular disease. However, the association of these adipocytokines with chronic kidney disease (CKD) is not clear. We examined the association of serum adiponectin, leptin levels and leptin to adiponectin ratio (LAR) with CKD in a population-based sample of Asian adults.. We conducted a case-control study (450 CKD cases and 920 controls matched for age, sex and ethnicity) involving Chinese and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases Study (2007-2011). CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73m2 from serum creatinine. Serum adiponectin and leptin levels were measured using commercially available ELISA. Odds ratio of CKD associated with elevated adiponectin and leptin levels were estimated using logistic regression models adjusted for age, gender, ethnicity, education, smoking, body mass index, diabetes, blood pressure, total and HDL cholesterol.. CKD cases had higher levels of leptin (mean [SD] 9.7 [11.5] vs.16.9 [20.2] ng/mL, p<0.0001) and adiponectin (10.4 [7.4] vs. 9.2 [4.2], p = 0.001) compared to controls. In multi-variable models, compared to those in the lowest quartile, the OR (95% confidence interval) of CKD among those in the highest quartile were: 6.46 (3.84, 10.88), 1.94 (1.32-2.85) and 2.88 (1.78-4.64) for leptin, adiponectin and LAR. Similar associations were also observed when adiponectin and leptin were analyzed as continuous variables. This positive association of serum adiponectin, leptin and LAR with CKD was consistently present in subgroups of gender, ethnicity, diabetes, hypertension and overweight status (all P-interaction >0.1).. Higher levels of serum adiponectin, leptin and LAR were positively associated with CKD independent of traditional risk factors in this Asian population.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Asian People; Case-Control Studies; Female; Glomerular Filtration Rate; Humans; Leptin; Male; Middle Aged; Renal Insufficiency, Chronic

Topics: Female; Humans; Leptin; Male; Renal Insufficiency, Chronic

The feasibility and benefits of lifestyle intervention in chronic kidney disease (CKD) patients who are obese has not been well studied. We examined the early effects of an exercise plus weight loss intervention on body composition, exercise capacity, metabolic parameters and kidney function in obese subjects with CKD.. Nine subjects (median age 57 years, body mass index (BMI) 43.9) underwent a lifestyle intervention program that included supervised aerobic exercise (i.e. ∼85% maximum heart rate) and dietary counseling (500 kcal reduction in daily caloric intake). Body composition (iDXA), exercise capacity (maximal oxygen consumption), quality of life, insulin resistance (Matsuda index), inflammation (high sensitivity C-reactive protein), adipokines (leptin and total adiponectin) and kidney function (iothalamate glomerular filtration rate) were measured at baseline and after 12 weeks of the intervention. Changes in parameters were compared using the Wilcoxon signed-rank test.. After 12 weeks of intervention, there was a significant decrease in BMI and fat mass (median -4.9 kg (25th-75th percentile -5.9 to -3.0)). There was a significant increase in exercise capacity (3.7 ml/kg/min (3.0-4.7)), along with improvements in insulin sensitivity (0.55 (0.43-1.2)), total adiponectin (780.9 μg/ml (262.1-1,497.1)) and leptin (-5.1 ng/ml (-14.5 to -3.3)). There were improvements in biomarkers of kidney disease very quality of life measures, but kidney function remained unchanged.. Lifestyle modification is feasible in obese patients with CKD and produces weight loss that is related to improvements in exercise capacity, insulin resistance and adipokines. Whether lifestyle-induced weight loss and fitness can be sustained and whether it will mediate improvements in kidney function over time merits further investigation.

Topics: Absorptiometry, Photon; Adiponectin; beta 2-Microglobulin; Blood Glucose; Body Composition; Body Mass Index; C-Reactive Protein; Cystatin C; Diet, Reducing; Exercise Therapy; Exercise Tolerance; Female; Glomerular Filtration Rate; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Life Style; Male; Middle Aged; Obesity; Quality of Life; Renal Insufficiency, Chronic

Elevated serum leptin levels correlate with inflammation and predict changes in lean body mass in patients with CKD, and activation of the melanocortin system by leptin signaling mediates the pathophysiology of CKD-associated cachexia. We tested whether treatment with a pegylated leptin receptor antagonist (PLA) attenuates cachexia in mice with CKD. CKD and Sham mice received vehicle or PLA (2 or 7 mg/kg per day). At these doses, PLA did not influence serum leptin levels in mice. Treatment with 7 mg/kg per day PLA stimulated appetite and weight gain, improved lean mass and muscle function, reduced energy expenditure, and normalized the levels of hepatic TNF-α and IL-6 mRNA in mice with CKD. Furthermore, treatment with 7 mg/kg per day PLA attenuated the CKD-associated increase in the transcriptional and protein abundance of uncoupling proteins that mediates thermogenesis, and it normalized the molecular signatures of processes associated with muscle wasting in CKD, including proteolysis, myogenesis and muscle regeneration, and expression of proinflammatory muscle cytokines, such as IL-1α, -1β, and -6 and TNF-α. Our results suggest that leptin antagonism may represent a viable therapeutic strategy for cachexia in CKD.

Topics: Animals; Anorexia; Cachexia; Energy Metabolism; Gene Expression; Leptin; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Receptors, Leptin; Renal Insufficiency, Chronic; Signal Transduction; Weight Loss

To investigate the relative associations of renal function, obesity, and inflammation with serum leptin levels in children with chronic kidney disease (CKD).. This was a cross-sectional analysis of 317 children from the Chronic Kidney Disease in Children study, a large cohort of pediatric patients with stage II-IV CKD. Linear regression modeling was used to evaluate the association of serum leptin level with glomerular filtration rate calculated using the plasma iohexol disappearance curve, demographics, body mass index (BMI), and cardiovascular risk factors, including inflammatory cytokines, insulin resistance, and serum lipid levels.. In univariate analyses, elevated serum leptin level was significantly associated with increased BMI, older age, and female sex (P < .001 for all). Leptin level also correlated positively with serum triglycerides and insulin resistance (P < .001) and negatively with serum high-density lipoprotein cholesterol (P = .002). Leptin level was not associated with glomerular filtration rate calculated using the plasma iohexol disappearance curve or inflammatory cytokines. In multivariate analysis, BMI, age, female sex, and serum triglyceride levels were significantly associated with serum leptin level.. Increased leptin production was associated with female sex, older age, and adiposity in children with mild to moderate CKD. Renal function was not associated with serum leptin level, indicating that decreased clearance does not contribute to elevated leptin levels.

Topics: Adolescent; Body Mass Index; Child; Cholesterol, HDL; Cohort Studies; Contrast Media; Cross-Sectional Studies; Cytokines; Dyslipidemias; Female; Glomerular Filtration Rate; Humans; Insulin; Insulin Resistance; Iohexol; Leptin; Linear Models; Male; Multivariate Analysis; Renal Insufficiency, Chronic; Risk Factors; Triglycerides

High body fat (BF) is an alarming condition that also affects nondialyzed chronic kidney disease (CKD) patients. Distinct methods are used to evaluate BF; however, in CKD population it remains unclear which one is more reliable showing high accuracy. Dual-energy X-ray absorptiometry (DXA), used as reference method to estimate adiposity, is expensive and time consuming to be applied in clinical settings. Recently, a new body adiposity index (BAI), that estimates BF from easily accessible measures, was validated in the general population. The aim of this study was to evaluate which simple and practical method, routinely used to estimate BF, shows the highest accuracy compared with DXA, in nondialyzed CKD patients.. In this cross-sectional study BF was estimated by DXA, bioelectrical impedance analysis (BIA), anthropometry (ANTHRO), and BAI. Serum leptin levels were determined.. Studied patients (n = 134) were 55% males, 54% overweight/obese, and 64.9 ± 12.5 years old, with estimated glomerular filtration rate (eGFR) = 29.0 ± 12.7 ml/min. The correlation coefficient was higher between DXA vs. ANTHRO (r = 0.76) and BAI (r = 0.61) than with BIA (r = 0.57), after adjusting for gender, age, and eGFR (P < 0.0001). Therefore, the Lin's concordance correlation coefficient and Bland-Altman plots were performed to measure the accuracy (C_b) between DXA with both ANTHRO and BAI. A higher accuracy (C_b = 0.82) and lower mean difference (-3.4%) was observed for BAI than for ANTHRO (C_b = 0.61; -8.4%). Leptin levels correlated (P < 0.0001) with DXA (r = 0.56) and BAI (r = 0.59).. These findings suggest that BAI estimates BF with high accuracy in nondialyzed CKD patients and may be helpful in the treatment of this population with increased BF.

Topics: Absorptiometry, Photon; Adipose Tissue; Adiposity; Aged; Anthropometry; Biomarkers; Body Mass Index; Cross-Sectional Studies; Electric Impedance; Evaluation Studies as Topic; Female; Humans; Leptin; Male; Middle Aged; Obesity; Overweight; Renal Insufficiency, Chronic

Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized.. We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors.. Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001) and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001) were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval) of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9) for leptin and 12.7 (6.5, 24.6) for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6). In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels.. These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.

Topics: Adiponectin; Adult; Aged; Female; Glomerular Filtration Rate; Humans; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Renal Insufficiency, Chronic; Resistin; Risk Factors; Severity of Illness Index

Adiponectin and leptin are two adipokines playing important roles in the regulation of body weight, appetite, carbohydrate and lipid metabolism. In patients with chronic kidney disease (CKD) adipokines accumulate in serum due to reduced renal clearance. Since adipokines have pleiotropic actions, the adipokine balance may have an impact on peritoneal membrane transport. The aim of this study was to assess whether serum adiponectin and leptin levels were related to peritoneal transport and residual renal function (RRF) in newly started peritoneal dialysis patients.. 25 clinically stable patients, 4 to 6 weeks after the onset of PD, were included in the study. For each patient clinical and laboratory data were reviewed and standard PET test was performed. Serum adiponectin and leptin concentrations were determined and leptin/adiponectin (L/A) ratio was calculated.. Serum adiponectin correlated negatively with weight, BMI and glucose concentration. Serum leptin and L/A ratio correlated positively with BMI. Serum adiponectin correlated positively with dialysate to plasma (D/P) creatinine ratio and ultrafiltration in PET test. Serum leptin level and L/A ratio correlated strongly negatively with peritoneal creatinine clearance.. Serum adiponectin concentration is positively associated with baseline solute transport. Leptin concentration and L/A ratio are negatively associated with dialysis adequacy in newly started PD patients.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Body Weight; Female; Humans; Leptin; Male; Membrane Transport Modulators; Middle Aged; Peritoneal Dialysis; Positron-Emission Tomography; Renal Insufficiency, Chronic

Recognition of adipose-related signaling in surgery is increasing, although direct interrogation of human adipose has been sparse. Few scenarios rival uremia for health impact. We hypothesized that adipose from uremic patients holds a relatively higher adipose-derived hormone and proinflammatory adipokine signature; we simultaneously evaluated the impact of clinical parameters on adipose phenotype.. Adipose was harvested from surgical patients. Histology and protein analyses were completed for select mediators.. In the overall cohort of 71 patients, the mean age was 63.4 y; 46.4% of patients had diabetes mellitus, 49.2% had hyperlipidemia, and 53.5% had coronary artery disease. Compared with nonuremic patients, uremic patients had one-tenth of the levels of leptin (P < 0.001), one-third of the levels of adiponectin (P < 0.001), and threefold higher levels of resistin (P < 0.001). Females had sixfold higher levels of leptin, 1.5-fold higher levels of adiponectin, and twofold higher levels of tumor necrosis factor alpha but equivalent resistin. There were differences in mediators when stratified by age. In both the obese and nonobese strata, we observed a concordant pattern of association (magnitude or significance) of uremia and leptin, adiponectin, and resistin. No differentials in other mediators emerged on body mass index stratification. Multiple regression analysis for leptin, adiponectin, and resistin (with age, gender, and uremia as independent variables) showed uremia as the highest independent predictor of all the three mediators.. Advanced chronic kidney disease is associated with perturbations in adipose-derived hormones (leptin, adiponectin, and resistin). Adipose adiponectin and leptin (in contrast to reported plasma levels) were lower in uremic patients; there is an inverse correlation between adipose resistin and renal function. Compared with other clinical parameters including body mass index, uremia dominates overall in determining adipose phenotype, highlighting the complex biological interplay between uremia and adipose biology.

Topics: Adiponectin; Aged; Aged, 80 and over; Cohort Studies; Female; Humans; Kidney; Leptin; Male; Middle Aged; Phenotype; Prospective Studies; Renal Insufficiency, Chronic; Resistin; Subcutaneous Fat; Uremia

Chronic low-grade inflammation and/or obesity are suggested to induce chronic kidney disease (CKD) in patients with type 2 diabetes. This cross-sectional study was performed to investigate the relationship between inflammatory biomarkers and CKD in non-obese patients with type 2 diabetes.. 106 non-obese Japanese patients with type 2 diabetes were recruited for the measurement of GFR, TNF, HMW adiponectin, leptin, hsCRP and some variables including urinary albumin. BMI, serum creatinine, and urinary albumin levels were 22.2 ± 0.2 kg/m(2) (17.1-24.9 kg/m(2)), 0.76 ± 0.02 mg/dl (0.39-1.38 mg/dl), 40.4 ± 4.3mg/gCr (1.6-195.0mg/gCr), respectively. They were stratified into two groups based on the value of eGFR: low eGFR (eGFR<60 ml/min/1.73 m(2)) and normal eGFR (eGFR>60 ml/min/1.73 m(2)). Logistic regression analysis was used for statistical analysis.. Whereas univariate logistic regression analysis showed that gender, diabetes duration, triglyceride, HDL cholesterol, uric acid, urinary albumin, and soluble TNF receptors (sTNF-R1, sTNF-R2) are associated with the development of stage 3 CKD, multivariate logistic regression analysis revealed that sTNF-R2 (Odds ratio 1.003, 95% confidence interval 1.000 to 1.005, P=0.030) showed significant associations with the development of stage 3 CKD.. Circulating TNF receptor 2 is an independent risk factor for CKD in non-obese Japanese patients with type 2 diabetes.

Topics: Adiponectin; Aged; Asian People; Creatinine; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Humans; Leptin; Male; Middle Aged; Obesity; Receptors, Tumor Necrosis Factor; Renal Insufficiency, Chronic

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

Protein-energy wasting is a common problem in pediatric patients with chronic kidney disease (CKD). Disturbances in appetite-regulating hormones have been suggested as causative factors. Acyl ghrelin is a potent orexigenic hormone, whereas desacyl ghrelin and obestatin have the opposite effect. The regulation of acyl ghrelin and its anorexigenic opponents and its role in the development of CKD-associated protein-energy wasting is poorly understood. We measured total and acylated ghrelin, obestatin, leptin, and adiponectin in children with CKD (n=29), children undergoing hemodialysis (HD) or peritoneal dialysis (PD; n=29), renal transplant recipients (RTx; n=91), and healthy controls (n=27), and analyzed the data in relation to body mass index (BMI) and height. Patients with renal insufficiency showed lower BMI standard deviation score (SDS) values and height SDS compared with controls and RTx patients. Total ghrelin was elevated in CKD and dialyzed patients compared with controls or transplant recipients (P<0.001). Acyl ghrelin did not differ between groups, and the acyl ghrelin/total ghrelin ratio was reduced in uremic patients (P<0.05). Obestatin plasma levels were increased in patients with renal insufficiency compared with controls and RTx patients (P<0.01). Uremia leads to an accumulation of the anorexigenic hormones desacyl ghrelin and obestatin. Orexigens like acyl ghrelin are not elevated. A disturbed balance between anorexigenic and orexigenic hormones may influence development of CKD-associated protein-energy wasting in pediatric patients.

Topics: Adiponectin; Body Height; Body Mass Index; Child; Female; Ghrelin; Humans; Leptin; Male; Renal Insufficiency, Chronic; Wasting Syndrome

This study was designed to investigate bone mineral density (BMD), growth parameters and biochemical markers in children with chronic kidney disease (CKD).. Sixteen patients, 4-18 years, with CKD were prospectively followed for 1 year. Auxological data, body composition, BMD by dual-energy X-ray absorptiometry, bone age, bone turnover markers, vitamin D, parathyroid hormone (PTH), leptin, osteoprotegerin, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were measured. A questionnaire regarding bone health and diet was also performed.. Delayed bone age was observed (n = 11) and the BMD Z-scores for total body were below zero in seven patients. However, total body BMD (TBBMD) increased in 12 patients. Most patients had increased osteocalcin and carboxy-terminal telopeptide of type I collagen, but normal alkaline phosphatase, type I procollagen intact amino-terminal propeptide and tartrate-resistant acid phosphatase 5b. Ten patients had increased PTH. Most children had normal levels of leptin, osteoprotegerin, IGF-I and IGFBP-3. Leptin, at baseline, correlated with differences in TBBMD over 1 year.. Only seven (44%) had negative Z-scores and TBBMD increased over 1 year. Bone markers at baseline did not predict the longitudinal changes in BMD.

Topics: Acid Phosphatase; Adolescent; Biomarkers; Bone Density; Child; Child, Preschool; Collagen Type I; Female; Humans; Isoenzymes; Leptin; Male; Parathyroid Hormone; Peptides; Prospective Studies; Renal Insufficiency, Chronic; Tartrate-Resistant Acid Phosphatase

The aim of the present study is: (i) to evaluate the serum concentrations of leptin and resistin in the paediatric patients with chronic renal impairment (CRI), on haemodialysis (HD) and on peritoneal dialysis (PD) treatment; (ii) to examine the relationship between these hormones; and (iii) to investigate the possible influence of these hormones on the insulin resistance and sensitivity indexes as well as on serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels.. In total, 52 patients (15 patients with CRI, 24 PD patients and 13 HD patients) and 23 healthy age- and sex-matched control subjects were included in the present study.. Homeostasis model assessment of insulin resistance (HOMA-IR) was higher than 2.5 in 47.1% of the patients. IGF-1 levels of patients with CRI, PD and HD patients were significantly lower than those in the controls (P < 0.001, P < 0.001, P < 0.001, respectively). The leptin levels of patients with CRI and on PD and HD treatment were significantly higher than the control group (P = 0.038, P = 0.002, P = 0.006, respectively). Similarly, serum resistin levels of patients with CRI and those of PD and HD patients were higher when compared with healthy controls (P = 0.037, P < 0.001, P = 0.005, respectively).. Leptin and resistin levels were increased in the children with CRF; however, this elevation was not found to be associated with hyperinsulinism. Further studies to explain the mechanisms and consequences of the accumulation of these hormones in CRF may provide the therapeutical approach aiming to normalize their circulating levels.

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Glucose; Humans; Leptin; Male; Renal Dialysis; Renal Insufficiency, Chronic; Resistin