Leptin and resistin levels and their relationships with glucose metabolism in children with chronic renal insufficiency and undergoing dialysis
ABSTRACT 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.
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ABSTRACT: Resistin is an adipocytokine that recently generated much interest. Because of the fact that inflammation, endothelial cell damage or injury is invariably associated with such clinical conditions as thrombosis, atherosclerosis and their major clinical consequences, that is, cardiovascular disease and resistin play a role in linking inflammation and cardiovascular disease, the aim of the study was to assess resistin in correlation with markers of inflammation, endothelial cell injury and residual renal function in haemodialysed (HD) patients. We assessed resistin, markers of coagulation: thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2; fibrinolysis: tPA, plasminogen activator inhibitor type 1, plasmin-antiplasmin complexes (PAP); endothelial function/injury: von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM); inflammation: high sensitivity C-reactive protein (hsCRP), tumour necrosis factor alpha and interleukin-6 (IL-6). Healthy volunteers and HD patients did not differ significantly regarding age, leucocyte count, serum iron, aspartate and alanine aminotransferases activities, calcium, cholesterol, tPA concentration. Triglycerides, CRP (assessed by high sensitivity method), phosphate, urea, creatinine, IL-6, tumour necrosis factor alpha, vWF, prothrombin fragments 1+2, TAT, PAP, thrombomodulin, ICAM, plasminogen activator inhibitor type 1 and resistin, were elevated in HD patients when compared with the control group. Serum albumin, total protein, haemoglobin and haematocrit were significantly lower in HD patients when compared with the control group. In HD patients with hsCRP 0e; 6 mg/L, resistin, IL-6, vWF and F1+2 were significantly higher, whereas tPA was significantly lower than in patients with hsCRP<6 mg/L. Moreover, HD patients with residual renal function have significantly lower resistin when compared with patients without it. Resistin was significantly higher in diabetics. In HD patients, resistin correlated significantly, in univariate analysis, with calcium, phosphate, PTH, TIBC, vWF residual renal function, urea, hsCRP, IL-6 and tended to correlate with tPA and ferritin. In the healthy volunteers, resistin was related to IL-6 and hsCRP. In multiple regression analysis, resistin was independently related to hsCRP, IL-6, residual renal function in HD patients. Elevated resistin related to markers of inflammation may represent a novel link between inflammation and adipocytokines in HD patients. Impaired renal function and inflammation are responsible for elevated resistin in HD patients.Nephrology 06/2007; 12(3):246-53. DOI:10.1111/j.1440-1797.2007.00782.x · 1.86 Impact Factor
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ABSTRACT: We sought to determine the prevalence of hyperinsulinemia and insulin resistance in pediatric patients with chronic kidney disease (CKD) stages 2-4. Data were collected on 43 subjects, aged 6-21 years with mean glomerular filtration rate (GFR) = 47 ml/min per 1.73 m(2) body surface area. Patients were grouped by body mass index (BMI) as either non-lean (>85th percentile) or lean (<or=85th percentile). Fourteen (33%) subjects had hyperinsulinemia, and seven (16%) had elevated homeostasis model assessment of insulin resistance (HOMA-IR). Non-lean subjects had a higher serum insulin level (21.0 microU/ml vs 13.4 microU/ml, P < 0.0001) and HOMA-IR (4.9 vs 3.2, P < 0.001) than lean subjects had. The prevalence of hyperinsulinemia was higher in non-lean patients (40%) than in lean patients (29%) but was not statistically significant. High HOMA-IR was present in six (40%) non-lean subjects and in one lean subject (P < 0.001). Correlation analysis demonstrated that serum insulin level was significantly associated with BMI, leptin and tumor necrosis factor (TNF)-alpha. Stepwise regression determined that increased BMI (P = 0.003) and TNF-alpha (P = 0.01) independently predicted higher insulin level in the whole cohort. Separate analysis for lean subjects showed no significant associations between serum insulin level and BMI; TNF-alpha was the only independent predictor of serum insulin (beta = 1.11, P = 0.01). We conclude that hyperinsulinemia and insulin resistance are frequent in pediatric CKD. In lean patients inflammation appears to be an important determinant of serum insulin level.Pediatric Nephrology 11/2007; 22(10):1751-6. DOI:10.1007/s00467-007-0533-z · 2.88 Impact Factor
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ABSTRACT: Patients with renal insufficiency often suffer from cachexia and growth retardation due to low appetite and increased resting metabolic rate. The neuroendocrine hormone ghrelin, a growth hormone secretagogue, enhances food intake, but its role in the development of a cachectic state in renal insufficiency is unclear. Objective. The aim of our study was to investigate the plasma concentration of total ghrelin and other hormones involved in appetite regulation in children with preterminal chronic renal failure (CRF, n = 24), children undergoing dialysis (n = 19), children after renal transplantation (RTx, n = 59) and healthy controls (n = 10). Total ghrelin was significantly elevated in CRF patients (1370 +/- 182 pg/ml; mean +/- SEM) when compared to control subjects (682 +/- 106 pg/ml; P = 0.016) or patients following RTx (859 +/- 51 pg/ml; P = 0.002). Furthermore, a negative correlation between glomerular filtration rate and total ghrelin was observed in CRF and transplant recipients (r = 0.36, P = 0.0006). BMI SDS (standard deviation score) is lower in CRF patients compared to the other groups (P < 0.0001). Leptin, adiponectin, blood glucose, insulin, IGF-I, IGFBP-3 and growth hormone concentrations did not differ among groups. We observed elevated ghrelin levels in uraemic patients despite poor appetite, but the underlying reasons remain unclear. Normal ghrelin levels can be re-achieved following RTx.Nephrology Dialysis Transplantation 09/2008; 24(2):643-6. DOI:10.1093/ndt/gfn529 · 3.49 Impact Factor