Estimated glomerular filtration rate is a poor predictor of the concentration of middle molecular weight uremic solutes in chronic kidney disease

Background: Uremic solute concentration increases as Glomerular Filtration Rate (GFR) declines. Weak associations were demonstrated between estimated GFR (eGFR) and the concentrations of several small water-soluble and protein-bound uremic solutes (MW500Da). Materials and Methods: In 95 CKD-patients (CKD-stage 2-5 not on dialysis), associations between different eGFR-formulae (creatinine, CystatinC-based or both) and the natural logarithm of the concentration of several LMWP's were analyzed: i.e. parathyroid hormone (PTH), Cystatin C (CystC), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), leptin, retinol binding protein (RbP), immunoglobin light chains kappa and lambda (Ig-kappa and Ig-lambda), beta-2-microglobulin (beta M-2), myoglobin and fibroblast growth factor-23 (FGF-23)). Results: The regression coefficients (R-2) between eGFR, based on the CKD-EPI-Crea-CystC-formula as reference, and the examined LMWP's could be divided into three groups. Most of the LMWP's associated weakly (R-2 0.7). Almost identical R-2-values were found per LMWP for all eGFR-formulae, with exception of CystC and beta M-2 which showed weaker associations with creatinine-based than with CystC-based eGFR. Conclusion: The association between eGFR and the concentration of several LMWP's is inconsistent, with in general low R-2-values. Thus, the use of eGFR to evaluate kidney function does not reflect the concentration of several LMWP's with proven toxic impact in CKD

Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease

Dialysis water and fluid purity: more than endotoxin

The evolution of extracorporeal treatment of end-stage renal failure has enforced focus on the purity of dialysis fluid. A major challenge of high-flux haemodialysis (HD) and haemodiafiltration relates to the necessity for ultrapure dialysis fluid and for sterile non-pyrogenic substitution fluid. The present review focuses especially on the possible microbial contamination including, next to intact micro-organisms, a variety of microbial derivatives. It is pointed out that there are conditions (e.g. contamination by non-culturable micro-organisms or bacterial derivatives other than lipopolysaccharides) where the detection of biologically relevant contaminants can be missed when applying the recommended standard detection methods such as bacterial culture and limulus amoebocyte lysate test. Possible approaches for action upon positive sampling results, exceeding the levels recommended in the latest ISO 11663:2009, are described in detail and illustrated with flow charts. The issue of purity of dialysis fluids is highly relevant, since the chronic exposure of HD patients to low levels of cytokine-inducing microbial components can significantly contribute to the micro-inflammatory status of these patients

Home haemodialysis and uraemic toxin removal: does a happy marriage exist?

Home-based methods of haemodialysis are becoming of increasing interest. In this article, we review theoretical and evidence-based aspects of dialysis adequacy in the home setting compared with those of standard in-centre dialysis. Owing to the flexibility it enables, home haemodialysis may allow reduced blood flow rates and the successful use of less-efficient access systems. With home haemodialysis, Kt/V-urea targets should be pursued as recommended in current guidelines, taking into account that this parameter does not reflect a number of essential elements that affect adequacy, such as dialyser pore size or alternative timeframes-factors that might be applicable to modern home haemodialysis. The use of high-flux, large-pore haemodialysers is associated with improved removal of large uremic toxins and should be considered as standard in home haemodialysis where possible, although dialysis water purity is crucial. Large molecule removal is further enhanced by applying convective strategies (such as haemo[dia]filtration), but these strategies greatly increase technical complexity. Alternate-day haemodialysis is more desirable than the usual thrice-weekly approach to avoid complications at the end of the long weekend interval, and it is easier to implement such a regime at home than in-centre. Frequent, prolonged, and combined frequent and prolonged dialysis regimes are all associated with improved removal and improved outcomes. All three alternative timeframes are easier to apply at home than in-centre. Home haemodialysis offers increased flexibility in adopting dialysis regimes that make it possible to improve solute removal and, therefore, outcomes