neuropeptide-y and Renal-Insufficiency--Chronic

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

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

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system.

Topics: Cognitive Dysfunction; Humans; Hypertension, Renal; Neuropeptide Y; Receptors, Neuropeptide Y; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors

Increased activity of the sympathetic nervous system (SNS) has been proposed as a risk factor for increased cardiovascular mortality in patients with chronic kidney disease (CKD). Information on the activity of cardiac sympathetic innervation is non-homogeneous and incomplete. The aim of our study was to evaluate the tonic effect of SNS on heart rate, norepinephrine turnover and direct and indirect effects of norepinephrine in left ventricles of subtotally nephrectomized rats (SNX) in comparison with sham-operated animals (SHAM). Renal failure was verified by measuring serum creatinine and urea levels. SNX rats developed increased heart rates and blood pressure (BP). The increase in heart rate was not caused by sympathetic overactivity as the negative chronotropic effect of metipranolol did not differ between the SNX and SHAM animals. The positive inotropic effects of norepinephrine and tyramine on papillary muscle were not significantly different. Norepinephrine turnover was measured after the administration of tyrosine hydroxylase inhibitor, pargyline, tyramine, desipramine, and KCl induced depolarization. The absolute amount of released norepinephrine was comparable in both groups despite a significantly decreased norepinephrine concentration in the cardiac tissue of the SNX rats. We conclude that CKD associated with renal denervation in rats led to adaptive changes characterized by an increased reuptake and intracellular norepinephrine turnover which maintained normal reactivity of the heart to sympathetic stimulation.

Topics: Animals; Calcitonin Gene-Related Peptide; Cardiovascular Diseases; Disease Models, Animal; Heart Rate; Heart Ventricles; Kidney; Male; Nephrectomy; Neuropeptide Y; Norepinephrine; Rats, Wistar; Renal Insufficiency, Chronic; Sympathetic Nervous System

Neuropeptide Y (NPY) is a multifaceted sympathetic neurotransmitter regulating reflex cardiovascular control, myocardial cell growth, inflammation and innate immunity. Circulating NPY levels predict cardiovascular mortality in patients with end stage kidney disease on dialysis but this relationship has never been tested in predialysis chronic kidney disease (CKD) patients.. We investigated the relationship between circulating NPY and the risk for cardiovascular events (Fine & Gray competing risks model) in a cohort of 753 stages 2-5 CKD patients over a median follow-up of 36 months.. Independently of other risk factors, plasma NPY was directly related with the glomerular filtration rate (β = -0.19, P < 0.001) but was independent of systemic inflammation as quantified by serum IL6 and C reactive protein. Over follow-up 112 patients had cardiovascular events and 12 died. In analyses fully adjusted for traditional risk factors and a large series of CKD-specific risk factors and considering death as a competing event (Fine and Gray model) a 0.25 μmol/l increase in NPY robustly predicted the incident risk for cardiovascular events (subdistribution hazard ratio: 1.25; 95% confidence interval: 1.09-1.44; P = 0.002). Furthermore, the fully adjusted NPY - cardiovascular outcomes relationship was modified by age (P = 0.012) being quite strong in young patients but weaker in the old ones.. NPY is an independent, robust predictor of cardiovascular events in predialysis CKD patients and the risk for such events is age-dependent being maximal in young patients. These findings suggest that NPY may play a role in the high risk of cardiovascular disease in this population.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Incidence; Male; Middle Aged; Neuropeptide Y; Renal Insufficiency, Chronic; Risk Factors

Loss of appetite affects one-third of patients with CKD and is the leading cause of malnutrition in this population. Orexigenic Agouti-related peptide (AgRP) with neuropeptide-Y (NPY) and anorexigenic melanocyte-stimulating hormone-α (MSH-α) with cocaine- and amphetamine-regulated transcript (CART) are known to regulate appetite. In this study, we aimed to evaluate the levels of these peptides in CKD patients compared to healthy subjects and demonstrate the effects of dialysis treatment and erythropoiesis-stimulating agent (ESA) therapy. The cross-sectional study is composed of consecutive inclusion of 20 healthy individuals, 20 predialysis CKD patients, 20 HD, and 20 peritoneal dialysis (PD) patients. Exclusion criteria were an active infection, history of malignancy, hypo- or hyperthyroidism, and diabetes. Patients on dialysis had targeted Kt/Vs. Demographic features and BMIs of the four groups were similar. Levels of AgRP, NPY, AMSH, and CART were significantly different between groups. Nondialysis CKD patients had significantly lower hypothalamic hormones compared to healthy individuals, HD and PD patients (P = 0.02, P = 0.03, and P = 0.07 for AgRP; P = 0.02, P = 0.01, and P = 0.09 for NPY; P = 0.02, P = 0.02, and P = 0.03 for AMSH; P = 0.02, P = 0.005, and P = 0.030 for CART). Dialysis patients with or without ESA treatment had similar hormone levels (P = 0.13 for AgRP; P = 0.11 for NPY; P = 0.23 for AMSH, and P = 019 for CART). Predialysis CKD patients have lower orexigenic and presumably indirectly lower anorexigenic peptides compared to healthy subjects and dialysis patients. ESA treatment does not affect these hypothalamic peptides in dialysis patients.

Topics: Adult; Agouti-Related Protein; alpha-MSH; Appetite; Case-Control Studies; Cross-Sectional Studies; Female; Hematinics; Humans; Hypothalamus; Male; Middle Aged; Nerve Tissue Proteins; Neuropeptide Y; Peritoneal Dialysis; Renal Insufficiency, Chronic

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that has been implicated in various disorders including obesity, gastrointestinal and cardiovascular diseases.. We investigated the relationship between circulating NPY and the progression of the glomerular filtration rate (GFR) and proteinuria and the risk for a combined renal endpoint (>30% GFR loss, dialysis/transplantation) in two European chronic kidney disease (CKD) cohorts including follow-up of 753 and 576 patients for 36 and 57 months, respectively.. Average plasma NPY was 104 ± 32 pmol/L in the first CKD cohort and 119 ± 41 pmol/L in the second one. In separate analyses of the two cohorts, NPY associated with the progression of the estimated GFR (eGFR) and proteinuria over time in both unadjusted and adjusted {eGFR: -3.60 mL/min/1.73 m2 [95% confidence interval (CI): -4.46 to - 2.74] P < 0.001 and -0.83 mL/min/1.73 m2 (-1.41 to - 0.25, P = 0.005); proteinuria: 0.18 g/24 h (0.11-0.25) P < 0.001 and 0.07 g/24 h (0.005-0.14) P = 0.033} analyses by the mixed linear model. Accordingly, in a combined analysis of the two cohorts accounting for the competitive risk of death (Fine and Gray model), NPY predicted (P = 0.005) the renal endpoint [sub-distribution hazard ratio (SHR): 1.09; 95% CI: 1.03-1.16; P = 0.005] and the SHR in the first cohort (1.14, 95% CI: 1.04-1.25) did not differ (P = 0.25) from that in the second cohort (1.06, 95% CI: 0.98-1.15).. NPY associates with proteinuria and faster CKD progression as well as with a higher risk of kidney failure. These findings suggest that the sympathetic system and/or properties intrinsic to the NPY molecule may play a role in CKD progression.

Topics: Aged; Cross-Sectional Studies; Disease Progression; Female; Glomerular Filtration Rate; Humans; Longitudinal Studies; Male; Middle Aged; Neuropeptide Y; Prognosis; Proteinuria; Renal Insufficiency, Chronic

Neuropeptide Y (NpY) is an important factor in neuropeptide signalling, and significantly change in the blood and cerebrospinal fluid (CSF) during chronic kidney disease (CKD) progression. However, the role of NpY remains unclear. We aimed to investigate the associations between NpY levels, nutritional status and cardiovascular disease (CVD) in patients with CKD.. In this cohort study, we performed Pearson's correlation analysis and multiple linear regressions to assess the relationship between CSF and serum NpY levels, as well as nutritional indices. Receiver operating characteristic curves were used to evaluate the sensitivity and specificity of CSF NpY levels. As NpY affects the cardiovascular system, Kaplan-Meier analysis was used to investigate the relationship between serum NpY levels and CVD.. CSF NpY levels and nutritional indices were related during CKD progression (energy intake: β=0.236, P<0.001; mid-arm muscle circumference: β=0.953, P=0.014; prealbumin: β=0.067, P<0.001), and had high specificity (79.9%). High serum NpY levels may be a risk factor associated with CVD (relative risk=1.8015, 95% confidence interval: 1.0509-3.0881).. Our results suggested a relationship between CSF NpY levels and nutritional indices in CKD patients. High serum NpY concentrations may be a risk factor associated with CVD.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; China; Cohort Studies; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neuropeptide Y; Nutritional Status; Prognosis; Prospective Studies; Renal Insufficiency, Chronic; Risk Factors; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Up-Regulation