Michał Chmielewski

Aspects of Immune Dysfunction in End-stage Renal Disease

End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area.

Muscle atrophy, inflammation and clinical outcome in incident and prevalent dialysis patients

BACKGROUND & AIMS Muscle wasting is considered the best marker of protein-energy wasting in end-stage renal disease (ESRD). We tested the usefulness of a simple observer subjective muscle atrophy (MA) grading in relation to morbidity and mortality in ESRD patients. METHODS In two different ESRD cohorts (265 incident patients starting dialysis and 221 prevalent hemodialysis patients), each patients degree of MA was visually graded by a trained nurse on a scale from 1 to 4 as part of the subjective global assessment. This score was confronted with inflammatory and nutritional indexes as well as objective measurements of muscle atrophy. Patients were then prospectively followed for up to four or six years, depending on the cohort. RESULTS Thirty percent of the incident and 39% of the prevalent patients presented signs of MA. Across worsening MA scale, nutritional and anthropometric markers of muscle loss were incrementally poorer. Inflammation markers as well as the proportion of women became progressively higher. Female sex, presence of cardiovascular disease, inflammation and low insulin-like growth factor-1 levels were associated with increased significant odd ratios of MA in each cohort. After adjustment for age, sex, inflammation, diabetes, cardiovascular disease, glomerular filtration rate and/or time on hemodialysis, the hazard ratio of death for moderate/severe MA was 2.62 (95% CI: 1.34, 5.13; p=0.001) and 3.04 (95% CI: 1.61, 5.71; p=0.0001) in the incident and prevalent cohorts respectively. CONCLUSION Increased MA is more common in female dialysis patients and associated with inflammation, poor nutritional and anthropometric status, as well as a 3-fold increased 4-6 year mortality. Our data support the use of frequent MA and/or nutritional assessments in the clinical practice.

Metabolic abnormalities in chronic kidney disease that contribute to cardiovascular disease, and nutritional initiatives that may diminish the risk.

Purpose of review Chronic kidney disease (CKD) is associated with a wide range of severe metabolic and nutritional disturbances that directly or indirectly contribute to left ventricular hypertrophy, ischemic heart disease, vascular calcification, heart failure and other manifestations of cardiovascular disease (CVD). The CVD mortality rate in CKD patients is far higher than in the general population, and CKD is today recognized as one of the most important risk factors for CVD. In this review, we discuss the links between metabolic abnormalities and CVD in CKD patients and nutritional initiatives that may reduce this risk. Recent findings Certain nontraditional risk factors, such as protein-energy wasting, inflammation, and biomarkers reflecting bone and mineral disorders, are strong predictors of CVD mortality in CKD patients. Although several small nutritional intervention studies have been performed and nutritional guidelines have been introduced in order to minimize metabolic disorders and improve nutritional status, they have so far not been proven to reduce morbidity nor mortality. Summary Although the pathophysiological mechanisms involved in the markedly increased CVD risk of CKD patients are becoming more evident, still few nutritional randomized controlled studies have been conducted in this high-risk patient group.

Associations of VEGF and its receptors sVEGFR-1 and -2 with cardiovascular disease and survival in prevalent haemodialysis patients

BACKGROUND Vascular endothelial growth factor (VEGF) was recently shown to predict survival in prevalent haemodialysis patients. Soluble VEGF receptors (sVEGFR)-1 and -2 are circulating endogenous modulators of VEGF activity. We thus studied the relationship between sVEGFR-1 and -2 and survival in a cohort of prevalent haemodialysis (HD) patients. METHODS Components of the VEGF system were measured (ELISAs) in 185 prevalent HD patients and levels related to clinical characteristics, biochemical markers and survival. The patients were followed up prospectively for a median 31 (20-37) months. RESULTS While ischaemic heart disease was independently associated with a lower sVEGFR-2 (OR = 2.75, P = 0.02), sVEGFR-1 was positively associated with IL-6 (rho = 0.22, P = 0.003) and white blood cell count (rho = 0.22, P = 0.002). In survival analysis, the patients with a high sVEGFR-1 level had a higher all-cause mortality (Kaplan-Meier Chi-Square = 5.6, P = 0.02) and a higher adjusted mortality risk (Cox HR = 1.93, P = 0.009) than those with low levels. CONCLUSION In the first clinical study of sVEGFR-1 and -2 in CKD, we found novel associations between the sVEGFRs and cardiac disease. This may be of clinical importance, as a high sVEGFR-1 was an independent risk factor for all-cause mortality.

Temporal discrepancies in the association between the apoB/apoA-I ratio and mortality in incident dialysis patients

Background.  In the general population, a high apoB/apoA‐I ratio is a strong risk factor for cardiovascular disease and mortality. However, whether this is the case in chronic kidney disease (CKD) patients is currently unknown.

Analysis of Outcomes of the NRS 2002 in Patients Hospitalized in Nephrology Wards

Introduction: Malnutrition is a common problem among hospitalized patients. In chronic kidney disease, it affects up to 50% of the population. Undernourishment has an adverse effect on prognosis and prolongs convalescence. The aim of the study was to test the effectiveness of NRS (Nutrition Risk Screening) -2002 in the assessment of risk of malnutrition for patients hospitalized in nephrology wards. The aim was to develop clinical characteristics of malnourished patients and to assess the relationship between nutritional status and patient outcome. Methods: The analysis included 292 patients, consecutively admitted to nephrology wards. NRS-2002 was assessed in comparison to subjective global assessment. Associations with patient characteristics and outcome were evaluated. Results: Out of all the respondents, 119 patients (40%) suffered from malnutrition. The NRS-2002 showed a very strong relationship with Subjective Global Assessment (SGA) (p < 0.0001). Malnourished patients were older, were characterized by a significantly lower body mass index (BMI), and had a much longer hospitalization duration. In multiple regression analysis, the presence of malnutrition proved to be an independent predictor of the duration of hospital stay. CONCLUSIONS: Malnutrition is highly prevalent among patients hospitalized in nephrology wards, and it affects the length of hospitalization. Identification of malnourished patients and patients at serious risk of malnutrition progression allows the implementation of appropriate nutritional intervention.

Lipoprotein Lipase 1595 C/G and Hepatic Lipase –480 C/T Polymorphisms – Impact on Lipid Profile in Incident Dialysis Patients

Background: Dyslipidemia is a common complication of chronic kidney disease. Lipoprotein lipase (LPL) 1595 C/G and hepatic lipase (HL) –480 C/T single nucleotide polymorphisms (SNPs) influence lipid profile and predisposition for cardiovascular disease in the general population. The present study was undertaken to clarify the impact of the two polymorphisms on lipid parameters and cardiovascular risk in incident dialysis patients. Methods: LPL 1595 C/G and HL –480 C/T SNPs were evaluated in 293 chronic kidney disease patients close to dialysis initiation. Associations with lipid parameters, presence of cardiovascular disease, and survival were assessed. Results: LPL 1595 C/G SNP was associated with significantly lower triglyceride levels [1.55 (1.00–2.20) vs. 1.90 (1.40–2.48) mM; p < 0.01], while HL –480 C/T polymorphism was associated with increased high density lipoprotein cholesterol concentration [1.30 (1.00–1.60) vs. 1.10 (0.90–1.40) mM; p < 0.05]. Neither of the polymorphisms showed any relationship with patient survival. Conclusions: LPL 1595 C/G and HL –480 C/T polymorphisms affect lipid profile in incident dialysis patients.

Mechanisms and clinical implications of lipid disorders in chronic kidney disease

Abstract Deranged lipid metabolism is a common complication of chronic kidney disease (CKD). Uremia, and metabolic and endocrinological disturbances associated with uremia, as well as the high prevalence of comorbidities, wasting and inflammation in CKD patients, all play their role in promoting and modifying CKD-associated dyslipidemia. However, the exact pathomechanisms leading to lipid disorders are still poorly understood. Similarly, the impact of lipid disturbances on patient outcome is unclear. Many studies in dialysis patients have documented the, so called, ‘reverse epidemiology’, with low plasma cholesterol being an apparent risk factor for mortality. Potential explanations for this phenomenon include confounding by wasting and comorbidities, reverse causation, and also causal relationships with hypocholesterolemia having a direct impact on poor outcome. To elucidate the question of ‘reverse epidemiology’ some novel approaches have been introduced, for example, Mendelian randomization and time-dependent conditional survival analysis. This review aims to outline the major mechanisms responsible for the uremic dyslipidemia, and will attempt to shed light on the issue of CKD-associated reverse association between lipid risk factors and mortality.

Contents Vol. 26, 2008

163 13th International Conference on Continuous Renal Replacement Therapies (CRRT) February 27–March 1, 2008, San Diego, Calif. Editor: Mehta, R.L. (San Diego, Calif.) (Available online only)