Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients. The Dutch CONvective TRAnsport STudy (CONTRAST).

Today, an increasing number of patients with end stage renal failure (ESRF) is treated with on-line hemodiafiltration (HDF). This practice is based on the assumption that the high incidence of cardiovascular (CV) disease, as observed in patients with ESRF, is at least partially related to the retention of uremic toxins in the middle and large-middle molecular (MM) range. As HDF lowers these molecules more effectively than hemodialysis (HD), it has been suggested that this treatment improves CV outcome, if compared to standard HD. Thus far, no definite data on the effects of HDF on CV parameters and/or clinical end-points are available.
As the accumulation of MM weight substances has been implicated in increased oxidative stress and endothelial dysfunction, a reduction of these compounds might improve these derangements. In addition, cardiac dysfunction, atherosclerosis (as measured by left ventricular mass index [LVMi], carotid intima media thickness [CIMT]) and vascular stiffness (as measured by pulse wave velocity [PWV]) might be reduced during HDF, as compared to low-flux HD.
Therefore, we propose a prospective, randomized multicenter trial, comparing (on-line) HDF with HD. After a stabilization period, an expected number of 800 chronic HD patients will be randomized to either HDF or low-flux HD for three years. Primary end points are all cause mortality and combined CV events and mortality. In addition, LVMi, PWV, CIMT and various parameters of oxidative stress, acute phase reaction (APR) and endothelial function will be assessed and compared between treatment groups.
This study will provide strong evidence on the efficacy of HDF compared to low flux HD on CV morbidity and mortality, which is currently lacking but urgently needed. It is possible that the outcome of this study will affect current clinical practice considerably. Moreover, the study will point towards the mechanisms underlying the effects of HDF.

The high incidence of cardiovascular disease in patients with end stage renal disease (ESRD) is related with the accumulation of uremic toxins in the middle and large-middle molecular weight range. As online hemodiafiltration (HDF) lowers these molecules more effectively than standard hemodialysis (HD), it is suggested that this treatment may improve cardiovascular outcome.

Patients will be randomised between:
- online hemodiafiltration
- (continuation with) low-flux hemodialysis