Clinical and biochemical aspects of hemodialysis and hemodiafiltration

Abstract

In hemodialysis (HD) clearance of uremic toxins occurs as a result of a concentration gradient between the blood and the dialysate, a process called diffusion. During hemodiafiltration (HDF), diffusion is combined with pressure driven fluid transport across the dialysis membrane, a process called convection. Convection increases removal of middle molecular weight toxins, and the combination with diffusion in HDF may have a beneficial effect on biochemical and clinical outcomes in dialysis patients. The CONvective TRAnsport STudy (CONTRAST) is a randomized clinical trial comparing morbidity and mortality between patients treated with low-flux HD and online HDF. In this thesis clinical and biochemical aspects of HD and HDF are described. Connective tissue growth factor (CTGF) is a profibrotic growth factor of middle molecular weight. CTGF plasma concentrations are elevated in patients with chronic kidney disease. We studied CTGF in HD patients and found that patients with plasma CTGF in the highest quartile had an increased risk for all-cause mortality. In patients treated with HDF, CTGF concentrations significantly decreased after a year of treatment as compared to patients treated with HD. It remains to be determined whether CTGF is a uremic toxin with pathologic effects or a biomarker reflecting fibrotic damage, which is associated with poor outcome. We found no difference in concentrations of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) and the negative acute phase protein albumin between the HD and HDF treated patients up to three and six years respectively. Irrespective of treatment, CRP, IL-6, albumin and body mass index (BMI) all deteriorated over time. We found an excess decline of albumin and BMI in older patients, in patients with diabetes mellitus and in men. Furthermore, we found a trend towards a larger increase of CRP and IL-6 in men as compared to women. HDF did not reduce all-cause mortality and fatal- and non-fatal cardiovascular (CV) events as compared to HD. In patients treated with the highest tertile of convection volume, post-hoc analysis showed that the risk of mortality was reduced by 38%. The risk of fatal- and non-fatal infections was not reduced by HDF. Of all infections, the category of respiratory infections was most common, followed by skin/musculoskeletal infections. Thirty-two percent of deaths was of cardiovascular origin, 23% of patients died after dialysis withdrawal and 22% died because of an infection. CV death was more common in patients <60 years old. The proportions of CV deaths in CONTRAST and the Dutch dialysis registry (Renine) were similar to the proportion of CV death of the general population of the Netherlands. The proportion of patients dying after dialysis withdrawal was higher than anticipated, these patients were older, had more comorbidity and a lower mental quality of life at the beginning of the study.