LAUSR

“Classic”, low-flux, hemodialysis (HD) was the most common form of renal-replacement-therapy for decades, offering appreciable prolongation of life to millions of patients with end-stage kidney disease (ESRD). However, the overall 5-year survival rate of HD patients is slowly improving over the years, currently reaching at best 40– 50% in different countries [1]; this comes in contrast with improvements in life-expectancy and quality of life in patients affected with other major diseases, especially many forms of cancer. Low-flux HD provides, through diffusion, effective clearance of low-molecular weight solutes, such as urea and creatinine, but much less or negligible clearance of middleand high-weight substances. As elevated levels of middle-weight molecules (i.e., β2microglobulin) in HD patients were associated with increased mortality in observational studies, it was hypothesized that better clearance of such solutes through high-flux HD, hemodiafiltration (HDF), and particularly online-HDF, which can add high convective volumes, would be associated with decreased cardiovascular events and mortality [2]. For several years, however, the issue of superiority of HDF over HD has been surrounded by substantial controversy. As in many other concepts involving real clinical practice, observational studies indicated that HDF improved intermediate and hard endpoints, but early clinical trials could not clarify the field due to limitations in methodology and reporting [2]. In recent years, 3 rigorously performed clinical trials were published, with 2 showing no difference and one suggesting a 30% reduction in mortality with online HDF [3]. Furthermore, a pooled individual data analysis including those 3 and a fourth trial involving a total of ∼2,800 patients and 2.5 years of follow-up showed that online HDF reduced the relative risks of all-cause and cardiovascular mortality by 14 and 23%, with the largest benefit in the patient subgroup of the highest convection volume (>23 L/1.73 m2/ session) where respective reductions of 22 and 31% were noted [3], as was the case in several observational efforts. Importantly, all these trials included patients with prevalent ESRD who were already on conventional HD and randomized them either to continue HD or switch over to online-HDF, and this could be considered a critical limitation.