Obese sarcopenia in patients with end-stage renal disease is associated with inflammation and increased mortality.

Background: Adipose tissue in overweight patients with end-stage renal disease (ESRD) is a source of proinflammatory mediators, which could contribute to protein-energy wasting (PEW), cardiovascular disease, and increased mortality. Overweight in ESRD patients, however, is reported to be associated with better survival.

Objective: We investigated the associations between overweight [body mass index (BMI; in kg/m2) > 25], inflammation, PEW, and mortality in ESRD patients starting dialysis.

Low-grade inflammation in chronic kidney disease patients before the start of renal replacement therapy: sources and consequences.

Low-grade inflammation is a common feature of chronic kidney disease (CKD) already before the start of renal replacement therapy, and evidence suggests that persistent inflammation may also be per se a risk factor for progression of CKD and vascular disease. Many factors, including retention of pro-inflammatory cytokines, advanced glycation end products, reactive oxygen species, autonomic dysfunctions and volume overload may contribute to inflammation when renal function declines. The aim of the present review is to summarize the causes and consequences of a chronic inflammatory state in the CKD population before start of renal replacement therapy, with special emphasis in polymorphnuclear leukocyte priming, which may be a key mediator in the induction of a vicious circle of oxidative stress and inflammation in CKD.

Statin treatment and diabetes affect myeloperoxidase activity in maintenance hemodialysis patients.

Myeloperoxidase (MPO), which is secreted during activation of neutrophils, may serve as one mechanistic link among persistent inflammation, oxidative stress, and cardiovascular disease. This study related MPO activity to inflammatory and oxidative stress biomarkers, comorbidity, and ongoing medication in prevalent hemodialysis (HD) patients. In a cross-sectional evaluation of 115 prevalent (vintage 25 mo) HD patients (62 men; 63 +/- 1 yr), data on comorbidity (Davies score), diabetes, medication (statins and antihypertensive drugs), nutritional status (subjective global assessment), blood lipids (cholesterol, HDL cholesterol, and triglycerides), inflammatory biomarkers (serum albumin, C-reactive protein, TNF-alpha, and IL-6), oxidative stress biomarkers (pentosidine, 8-hydroxydeoxyguanosine, and MPO activity) were recorded.

Plasma pentraxin 3 in patients with chronic kidney disease: associations with renal function, protein-energy wasting, cardiovascular disease, and mortality.

Background And Objectives: Plasma protein pentraxin 3 concentrations are elevated in a wide range of diseased states. However, no study has evaluated protein pentraxin 3 in patients with chronic kidney disease.

Design, Setting, Participants, & Measurements: Plasma protein pentraxin 3 concentrations were analyzed in relation to GFR, inflammation, cardiovascular disease, and protein-energy wasting in 71 patients with stages 3 to 4 chronic kidney disease, 276 patients with stage 5 chronic kidney disease, and 61 control subjects.

Polymorphisms in cytokine genes influence long-term survival differently in elderly male and female patients.

Objectives: We asked if single nucleotide polymorphisms (SNP) in inflammatory cytokine genes related to 3-year survival in ill elderly subjects and if genotypes differed between the elderly and a younger control population.

Design: Prospective observational study.

Setting: Two geriatric departments at a university hospital.

Cytokine gene polymorphism and progression of renal and cardiovascular diseases.

Cytokines are important modulators of inflammation. The balance between pro- and anti-inflammatory cytokines determines whether the intensity of inflammatory response is within physiological limits or in the pathological range. The cytokine network is highly complex, containing interactive cascades of gene activation and suppression.

Association between oestrogen receptor alpha gene polymorphism and mortality in female end-stage renal disease patients.

Background: In the general population, genetic variations in the oestrogen receptor alpha (ERalpha) 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 ERalpha 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).

Impact of inflammation on epigenetic DNA methylation - a novel risk factor for cardiovascular disease?

Objective: The lifespan of dialysis patients is as short as in patients with metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA methylation is an important cellular mechanism modulating gene expression associated with ageing, inflammation and atherosclerotic processes.

Design: DNA methylation was analysed in peripheral blood leucocytes from three different groups of chronic kidney disease (CKD) populations (37 CKD stages 3 and 4 patients, 98 CKD stage 5 patients and 20 prevalent haemodialysis patients).

Comparison of nutritional and inflammatory markers in dialysis patients with reduced appetite.

Background: Anorexia is common in chronic kidney disease and worsens as the disease progresses. Sex hormones and inflammatory cytokines may be related to feeding behavior.

Objective: We hypothesized that appetite would be related to inflammation and outcome in hemodialysis patients but that sex may account for differences in the symptoms associated with poor appetite.

Associations between the CYBA 242C/T and the MPO -463G/A polymorphisms, oxidative stress and cardiovascular disease in chronic kidney disease patients.

Genetic variations in the NADPH/MPO system in chronic kidney disease (CKD) patients might lead to altered activity of these enzymes, and thus to altered risk for oxidative stress (OS) and cardiovascular disease (CVD). We evaluated the impact of 242C/T CYBA and -463G/A MPO polymorphisms on OS and CVD mortality in stage 5 CKD patients starting dialysis. Two hundred and fifty-seven patients were genotyped using Pyrosequencing.

Insulin resistance is associated with circulating fibrinogen levels in nondiabetic patients receiving peritoneal dialysis.

Background: Insulin resistance (IR) and inflammation are associated with increased risk of cardiovascular disease in the general population. Continuous glucose absorption in peritoneal dialysis (PD) may induce hyperglycemia and hyperinsulinemia.

Methods: We evaluated IR in nondiabetic patients receiving PD, and analyzed the association between IR and systemic inflammation biomarkers by performing a cross-sectional study on ambulatory dialysis.

Overestimation of advanced oxidation protein products in uremic plasma due to presence of triglycerides and other endogenous factors.

Background: Advanced oxidation protein products (AOPP), a suggested protein biomarker of oxidative stress, are elevated in patients with chronic kidney disease (CKD), who also often suffer from hypertriglyceridemia.

Methods: The analysis included plasma AOPP, TG, cholesterol, albumin and total protein, inflammation and oxidative stress markers from healthy subjects, non-dialyzed CKD, HD and CAPD patients. We studied, at two different European centres, effects of a meal, comparison between serum and plasma, L-index (indicating turbidity), spiking with fat and protein, and centrifugation on the AOPP concentrations.

Circulating levels of visfatin/pre-B-cell colony-enhancing factor 1 in relation to genotype, GFR, body composition, and survival in patients with CKD.

Background: Visfatin, also known as pre-B-cell colony-enhancing factor 1 (PBEF-1), recently was shown to be secreted from adipocytes and have insulin-mimetic properties in mice. Because renal failure per se is associated with both increased levels of circulating peptides and marked insulin resistance, even in the absence of diabetes mellitus, we hypothesized that visfatin could be a factor linking inflammation, kidney disease, and insulin resistance in this patient group.

Methods: Altogether, we studied 189 patients with chronic kidney disease (CKD), comprising 149 patients with CKD stage 5 (glomerular filtration rate [GFR] < 15 mL/min; mean, 7 +/- 2 mL/min [<0.

Use of single-nucleotide polymorphisms in the search for genetic modifiers of the uremic phenotype.

As the modern nephrology community continues to be burdened with growing numbers of patients with end-stage renal disease (ESRD) and exceptionally high mortality rates, it is obvious that progress in the development of preventive and therapeutic strategies has not been sufficient. This urges nephrologists to focus on the underlying mechanisms for ESRD morbidity and mortality, and in particular on cardiovascular disease (CVD), which is the major contributor to premature death in this patient group. The high prevalence of inflammation, vascular ossification, and oxidative stress in ESRD predisposes these patients to CVD.

Plasma pentosidine and total homocysteine levels in relation to change in common carotid intima-media area in the first year of dialysis therapy.

Background: Homocysteine and advanced glycation end-products (AGEs), which accumulate in chronic kidney disease (CKD), are recently proposed cardiovascular risk factors. In this study, we evaluated the association between changes in calculated intima media (cIM) area of the common carotid artery during the first year of dialysis therapy and plasma total homocysteine (tHcy) level as well as circulating AGEs such as plasma pentosidine level.

Methods: We studied 63 CKD patients (38 males) aged 52 +/- 12 years at a time-point close to start of dialysis treatment and after 12 months of dialysis treatment (41 on peritoneal and 22 on hemodialysis).

Changes in fat mass correlate with changes in soluble sCD163, a marker of mature macrophages, in patients with CKD.

Background: Recently, adipose tissue was shown to contain macrophages capable of contributing to systemic inflammation and cardiovascular disease (CVD). Here, we investigate this putative relationship in patients with chronic kidney disease (CKD) by using the novel macrophage marker soluble (s)CD163.

Methods: One hundred twenty patients with CKD stage 5 (mean glomerular filtration rate [GFR], 7 +/- 1 mL/min [0.

Peroxisome proliferator-activated receptor-gamma agonists diminish peritoneal functional and morphological changes induced by bioincompatible peritoneal dialysis solution.

Background: To evaluate if peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists have a potential protective effect on the peritoneum changes induced by bioincompatible peritoneal dialysis (PD) solution in vivo.

Methods: Male Wistar rats were dialyzed three times daily for 28 days with 1.36% Dianeal (two groups: with (D+R) or without (D) rosiglitazone) or 1.

Place of genotyping and phenotyping in understanding and potentially modifying outcomes in peritoneal dialysis patients.

With the landmark publication of the human genome sequence and its subsequent division into haplotype blocks, the characterization of genetic variations is becoming a feasible approach to study both the pathophysiology and risk factors of complex traits. A number of strategies are available today for identifying candidate genes or polymorphisms associated with pertinent phenotypes. For Mendelian diseases with high penetrance owing to mutations in a single gene, such as polycystic kidney disease, linkage studies have been very successful in mapping the disease loci owing to the availability of families with multiple affected members.

J-shaped mortality relationship for uric acid in CKD.

Background: Hyperuricemia is a common feature in patients with chronic kidney disease (CKD). Hyperuricemia has been associated with increased cardiovascular mortality in the general population, but less is known about this association in patients with CKD.

Methods: To explore possible associations of serum uric acid with all-cause mortality and comorbidity in patients with CKD, we studied 294 incident patients with CKD stage 5 (185 men; age, 53 +/- 12 years) starting renal replacement therapy with a median glomerular filtration rate of 6.

Elevated serum 8-oxo-dG in hemodialysis patients: a marker of systemic inflammation?

Does inflammation, as assessed by high sensitivity C-reactive protein (hs-CRP), in patients with end-stage renal disease (ESRD) tightly associate with increased serum levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8- oxo-dG)? Increased oxidative stress and inflammation have both been highlighted among several nontraditional risk factors for cardiovascular disease, which is the main cause of mortality in ESRD patients. In contrast to oxidative stress effects on proteins and lipids, DNA base damage has not been well demonstrated in ESRD. Two groups of hemodialysis patients were studied, one group with persistent inflammation (n = 13, with constant elevation of CRP > 10 mg/L for 6 months) and one group of noninflamed patients (n = 19, with constant CRP < 10 mg/L for 6 months).

The reverse epidemiology of plasma total homocysteine as a mortality risk factor is related to the impact of wasting and inflammation.

Background: The reason(s) for the apparently paradoxical 'reverse' association in end-stage renal disease (ESRD) patients in whom a low, rather than a high, total plasma total homocysteine (tHcy) level is an indicator of poor outcome remains unclear. The aim of this study was to examine whether the inverse association maintains, mitigates or reverses after comprehensive multivariate adjustment for the presence of wasting and inflammation as well as other potential confounders.

Methods: We studied 317 ESRD patients starting dialysis therapy.

Changes in fat mass after initiation of maintenance dialysis is influenced by the uncoupling protein 2 exon 8 insertion/deletion polymorphism.

Background: A high body mass index (BMI) has been reported to confer a survival advantage in end-stage renal disease (ESRD) patients. On the other hand, body fat accumulation, especially visceral adipose tissue, is an important risk factor for cardiovascular disease, as well as a clinically important source of adipokines. Uncoupling protein 2 (UCP2) uncouples respiration from ATP synthesis, thus regulating energy expenditure and fat oxidation.

Adipose tissue and inflammation in chronic kidney disease.

Cardiovascular disease remains a major cause of morbidity and mortality in end-stage renal disease patients. As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of cardiovascular disease in this high-risk population, inflammation (interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Recent studies show that the adipose tissue is a complex organ with functions far beyond the mere storage of energy.

New insights on inflammation in chronic kidney disease-genetic and non-genetic factors.

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in chronic kidney disease (CKD). As traditional risk factors cannot alone explain the unacceptable high prevalence and incidence of CVD in this population, inflammation (which is interrelated to insulin resistance, oxidative stress, wasting and endothelial dysfunction) has been suggested to be a significant contributor. Indeed, several different inflammatory biomarkers, such as high sensitivity C-reactive protein (CRP) has been shown to independently predict mortality in CKD patients.