The rationale and clinical potential of on-line hemodiafiltration as renal replacement therapy.

On-line hemodiafiltration (ol-HDF) was developed in the 1980s in response to the unmet medical needs observed with conventional low- and high-flux hemodialysis. Firstly, the limited overall efficacy of conventional HD treatment programs as compared to native kidney function has been consistently documented over the broad MW spectrum of uremic toxins as well as fluid volume and hemodynamic control. Secondly, the unphysiological profile of intermittent treatment leading to repetitive dialysis-induced hemodynamic stress is now a well-recognized component of cardiovascular disease and end organ damage. Thirdly, the bioincompatibility of patient-dialysis system leading to dialysis-induced biological reactions also identified as contributing to dialytic morbidity and mortality. To overcome these limitations and pitfalls, alternative convective-based therapies (hemofiltration and hemodiafiltration), using higher hemoincompatible membranes and ultrapure dialysis fluid, were proposed as a solution to enhance and enlarge MW spectrum of uremic compounds cleared and to reduce dialysis-patient biological interactions. In this context, online HDF appeared soon as the best viable and efficient renal replacement modality to cover these needs. Clinical development and implementation of ol-HDF showed also that dialytic convective dose matters with a threshold point (23 L/1.73 m 2 in postdilution mode) to observe clinical benefits and outcomes improvements.