The Immune System in End Stage Chronic Kidney Disease (CKD) Patients - Comparison Among Different Modalities of Renal Replacement Therapy (RRT)

The sustained inflammatory state in CKD is of complex pathogenesis and is believed to be in part attributable to the augmented activation of innate immune system cell subsets. The activation of the innate immune system plays an essential role within all the spectrum of cardiovascular disease in CKD, including accelerated atherosclerosis, left ventricular hypertrophy and heart failure. However, the intricate immunological mechanisms involved in the pathogenesis of CKD-associated cardiovascular disease remain to be clarified.The hemodialysis procedure itself is associated with an increased inflammatory burden. Considering the fact that middle molecules lie at the crossroads of chronic inflammation and immune dysregulation, oxidative stress as well as cardiovascular morbidity of CKD, efforts have focused on improving the clearance of larger middle molecules in dialysis. Hemodiafiltration is considered to further improve the clearance of larger toxins by utilizing large-volume ultrafiltration, also known as convection. HDF compared with standard hemodialysis, may have beneficial effects with regard to micro-inflammation, as indicated by lower levels of inflammatory markers, C-reactive protein (CRP), and Interleukin 6 (IL-6). However, evidence from large outcome trials comparing HDF to hemodialysis is controversial The introduction of the newest generation of highly selective and permeable MCO, which have an increasingly porous membrane but with tightened distribution of pore sizes, is associated with increased removal of large middle-molecules up to a molecular weight of 45,000 Dalton (Da). On the other hand safety concerns regarding MCO membranes such as albumin loss and back filtration of endotoxins have proven to be inconsistent by clinical studies run so far. Accordingly the clinical benefits of MCO membranes with regard to patient outcomes,chronic inflammation, immune dysregulation, atherosclerosis or structural heart disease, remains to be evaluated by future clinical studies. Until now there are no data regarding the effects of expanded hemodialysis on immune cell subsets or comparative studies regarding the influence of the currently available methods of RRT on immune cell subsets with expanded hemodialysis. Whether expanded hemodialysis with MCO membranes is associated with "improved" patterns of immune cell subsets with regard to chronic micro-inflammation as compared to the currently available methods, including HDF, and whether this translates into improved clinical outcomes remains to be elucidated, this being the aim of our study.

30 patients undergoing conventional hemodialysis and 15 patients undergoing PD will be enrolled in the study. The study will be designed in two arms - the cross-sectional arm and the prospective arm during which patients will be under follow-up for 12 months.

The cross-sectional study:

Immune cell subtypes will be measured at baseline in all patients. In patients undergoing hemodialysis, measurements will be performed in the midweek dialysis session and for PD patients during a programmed visit at the PD unit.

Regarding patients undergoing conventional hemodialysis: