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The article focuses on clinical trials on ghrelin for the treatment of uremic anorexia and wasting. A study by A. Yoshimoto et al. found that predominant accumulation of the desacyl form of ghrelin happens when renal function fails. A research by K. Wynne et al. demonstrated that the administration of acyl ghrelin in patients on peritoneal dialysis resulted in an increase in food and energy intake. According to a study by D. R. Ashby et al., the administration of acyl ghrelin raised the acyl ghrelin to total ghrelin ratio.

Background. Chronic inflammation influences renal anaemia and reduce erythropoetin effectiveness. Chronic kidney disease and haemodialysis (HD) induce elevated cytokine and C-reactive protein (CRP) levels at an inter-individually variable extent. These differences are in part due to polymorphisms within cytokine genes, e.g. for pro-inflammatory interleukin-6 (IL-6) and anti-inflammatory interleukin-10 (IL-10). We hypothesized that these polymorphisms influence erythropoetin effectiveness. Methods. Genotyping for polymorphisms of IL-6 (−174G/C) and IL-10 (−1082G/A) genes was done in 460 prevalent HD patients. Erythropoetin requirements were determined after three months of stable dosing of erythropoesis stimulating proteins (ESP). The effect of the cytokine genotypes was evaluated by multiple regression analysis. Results. The presence of the IL-6 –174G allele (found to be related with higher secretion of IL-6) was associated with a 26% higher ESP dose compared with individuals without the G allele (P = 0.008). The IL-10 –1082 G/A polymorphism was not associated with ESP needs. Multivariate analysis detected a predictive value for ESP dose of the IL-6 polymorphism (P = 0.022), the haemoglobin level and the dose of i.v. iron, but not of age, gender, dialysis vintage, ferritin or the CRP value. Conclusions. Presence of the IL-6 allele –174G is related to higher ESP doses in chronic HD patients. The polymorphism of the anti-inflammatory IL-10 does not influence ESP dose, probably due to the fact that this cytokine has directly inhibitory effects on haematopoiesis in addition to its beneficial effects on inflammation. [ABSTRACT FROM AUTHOR]

AbstractBackground:Bone and mineral disorders may contribute to extraosseous ossifications and cardiovascular disease (CVD) in end-stage renal disease (ESRD) patients. We have investigated the relationship between bone mineral density (BMD) and inflammation, wasting, CVD and mortality in ESRD patients. Methods:BMD (dual energy X-ray absorptiometry) and biochemical, nutritional and inflammatory markers were assessed in 277 incident ESRD patients (GFR 7.1 ± 0.2 ml/min) who were then followed prospectively for a mean of 27 (range 1–60) months. Carotid plaques were determined in 103 patients. Results:Patients with carotid plaques, clinical manifestation of CVD and wasting (assessed by subjective global assessment) had significantly lower BMD than their counterparts. Low BMD was associated with high all-cause and cardiovascular mortality. Even after adjustment for several confounders and risk factors, all-cause (HR = 2.1, CI: 1.1–3.9, p = 0.02) and cardiovascular (HR = 2.8, CI: 1.2–6.3, p = 0.02) mortality remained significantly associated with low BMD. Conclusions:Low BMD is associated with wasting and CVD, and is an independent predictor of all-cause and cardiovascular mortality in ESRD patients.Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractAs the kidney is the major site for elimination of many cytokines, the delicate equilibrium of pro-inflammatory cytokines and their inhibitors is clearly dysregulated in chronic kidney disease (CKD) patients. The consequences of the altered immune response in uremia lead to a state of persistent inflammation which is highly prevalent among CKD patients and is linked to complications such as the development of protein-energy wasting and atherosclerotic vascular disease. The present review aims at reviewing this complex orchestration of uremic cytokines beyond the well-studied interleukin-6 and tumor necrosis factor-α. Finally, we update our current understanding on anti-inflammatory treatment strategies in CKD patients, including nutritional and lifestyle measurements, pharmacological intervention and specific anticytokine strategies targeting the dialytic procedure.Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Inflammatory markers predict mortality in hemodialysis (HD) patients, whereas a possible association between oxidative stress (OS) markers and survival is less clear. We assessed the impact on all-cause mortality of baseline inflammatory [high-sensitivity C-reactive protein and interleukin-6 (IL-6)] and OS markers (advanced oxidation protein products, pentosidine, homocysteine) in 112 HD patients. We found no significant correlations between inflammatory and OS markers. During the 5.5 years of follow-up, 51 patients died. In a Kaplan-Meier analysis, the survival rate was reduced in patients with IL-6 higher than the median (IL-6 >4.2 pg/ml) (log- rank = 6.47; p = 0.01), in diabetics (log-rank = 12.26; p = 0.0005) and in older patients (log-rank = 11.22; p = 0.0008). Moreover, in Cox analysis only IL-6 and age were independently associated with mortality. We conclude that in this group of prevalent Brazilian HD patients, IL-6 was a better predictor of survival than other inflammatory and OS markers.Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Type-2 diabetes and diabetic kidney disease have additive effects on cardiovascular risk. Furthermore, the degree of proteinuria is an independent predictor of mortality in this patient group. We hypothesized that altered kidney clearance and/or metabolism of vasoactive peptides occurring during proteinuria could link early diabetic nephropathy to cardio vascular disease (CVD). Methods. We performed a cross-sectional study of 85 incident patients (51 ± 5 years, 49 males) with type-2 diabetes and 38 age- and sex-matched controls. We further divided patients by the presence of minor (<500 mg/day; n = 40) or severe (≥500 mg/day; n = 45) proteinuria. Clinical and anthropometric data, along with ultrasonographic flow-mediated dilatation (FMD) of the brachial artery and carotid intima-media thicknesses (CIMT), were recorded in each group. Circulating NAMPT/visfatin, adiponectin (normalized to BMI), AHSG/fetuin-A and hsCRP levels were also measured using commercial ELISA. Results. Plasma NAMPT/visfatin, CIMT, HOMA index and hsCRP levels were all significantly higher in diabetics than in control subjects, and all but CIMT correlated with proteinuria (ρ = 0.46; P < 0.001, ρ = 0.54; P > 0.05, ρ = 0.32; P = 0.003, ρ = 0.76; P < 0.001, respectively). FMD, adiponectin and AHSG/fetuin-A levels were significantly lower, and negatively correlated with proteinuria (ρ = −0.54; P < 0.001, ρ = −0.56; P < 0.001, ρ = −0.48; P < 0.001, respectively). In a multivariate regression analysis, the degrees of proteinuria (r2 = −0.32, P = 0.04) and plasma levels of NAMPT/visfatin (r2 = −0.33, P = 0.006) were independently related to FMD. Conclusions. The present study suggests that the presence of proteinuria, regardless of the degree of renal function impairment, is an important predictor of endothelial dysfunction in early diabetic nephropathy and that it is associated with altered circulating levels of NAMPT/visfatin and adiponectin. [ABSTRACT FROM AUTHOR]

Background. Endothelial dysfunction (ED) is common in patients with moderate to advanced chronic kidney disease (CKD). Recently, visfatin, a protein with insulin-mimetic properties, was shown to be associated with sVCAM-1. Thus, we hypothesised that visfatin may be a marker of ED in CKD. Methods. We studied 406 patients with different stages of non-diabetic CKD (50% males, 46 ± 12 years), testing the relationship between flow-mediated dilatation (FMD), assessed by high resolution brachial ultrasonography, and plasma adiponectin and visfatin concentrations. Eighty healthy volunteers (50% males, 46 ± 11 years) served as matched controls. Results. Compared to healthy controls, ED was observed in all stages of CKD (Stages 1–5) and correlated strongly with the reduction in estimated glomerular filtration rate (eGFR). Whereas visfatin concentrations were found to be increased in all but CKD stages 1 and 2, adiponectin levels were found to be increased in all patients but CKD stage 1. Visfatin and adiponectin levels were strongly correlated with eGFR (rho = −0.62 and rho = −0.72, respectively, P P P P P P P P Conclusions. We conclude that the circulating levels of visfatin and adiponectin are associated with ED in all stages of CKD, independently of inflammation and insulin resistance. [ABSTRACT FROM AUTHOR]

Background. In the general population, genetic variations in the oestrogen receptor α (ERα) gene may influence lipid abnormalities, cardiovascular disease (CVD), and mortality, but this has not previously been studied in end-stage renal disease (ESRD) patients. Methods. A total of 227 ESRD (141 men and 86 women) patients starting renal replacement therapy (RRT) were genotyped for three ERα gene polymorphisms (Ser10Ser, PvuII and XbaI) and the associations between these polymorphisms and clinical and laboratory parameters and survival were analysed. Patients were followed for a median period of 55 months (range 1–126 months). Results. The PvuII and XbaI polymorphisms were not associated with any of the clinical parameters. The ERα Ser10Ser CC genotype was present in 24 (28%) of the female and in 37 (26%) of the male patients. When comparing the CC genotype with the CT and TT genotypes, there were significant differences in lipid levels and inflammatory marker levels, especially in female patients. In female patients, the CC genotype was associated with lower prevalence of protein energy wasting (PEW) (17.4% vs 43.1%; P = 0.03), lower median serum triglyceride (1.7 vs 2.1 mmol/l; P = 0.001), higher median serum albumin (34.0 vs 32.5 g/l; P = 0.03) and lower median high sensitivity-CRP (hsCRP) (2.2 vs 5.5 mg/l; P = 0.03) levels compared with the CT plus TT genotypes. In male patients only HDL-cholesterol and ApoA levels were associated with this polymorphism. Whereas this polymorphism did not influence survival in males, the mortality was lower in female patients with the CC genotype (Kaplan–Meier; Log-rank 2.2, P = 0.02). Moreover, female patients with the CT plus TT genotypes had a borderline significant increased relative risk (Cox hazard model; 6.6, 95% CI: 0.87–49.9 P = 0.06) of death as compared with those with the CC genotype, even after adjustment for age and prevalence of CVD. Conclusions. Female, but not male ESRD patients with the ERα Ser10Ser CC genotype had lower prevalence of PEW, lower serum triglyceride, higher serum albumin and lower hsCRP levels. As this genotype was associated with a significantly decreased risk of all-cause death during the initial years of RRT, its protective properties need further study. [ABSTRACT FROM AUTHOR]