**6. Conclusions**

decrease in therapy‐related hypotension (RR 0.55) and cardiovascular mortality (RR 0.84) was reported. The authors concluded that convective therapies were associated with improved clearance of uremic solutes, but the potential long‐term benefits of specific convective modal‐

Wang et al. [68] conducted a systematic review and meta‐analysis that included 16 trials and 3220 patients treated with convective‐based therapies (HDF and HF) and with standard HD (low- and high-flux). Convection volume was not considered as a confounder in this analysis. On the one hand, the authors concluded that convective modalities did not significantly reduce the risk of cardiovascular events (RR 0.85) or all‐cause mortality (RR 0.83). On the other hand, they noted that convective modalities reduced intradialytic symptomatic hypotension (RR

Mostovaya et al. [69] compared exclusively HDF to HD (low- and high-flux) including 2402 patients. The meta‐analysis identified six RCTs. The convective arm consisted exclusively of HDF patients treated with different HDF modes (a mixture of postdilution, mid‐dilution, and predilution HDF, and of online HDF and HDF with bags) and achieving a specified minimum convection volume. All‐cause and cardiovascular mortality were reduced with HDF compared

Nistor et al. [70, 71] from the Cochrane group updated the previous systematic review of 2005 and compared HD (low- and high-flux) to convective‐based modalities (HF, AFB, bag HDF, and online HDF) without considering convection volume. Thirty‐five trials (4039 patients) were included in this meta‐analysis and the effects on mortality were estimated. The convective group consisted of 1648 patients, but 227 of them were treated with low convection volumes. Within the limitations of the review (e.g., studies reviewed were partially old and referred to a diverse mixture of HDF modalities), the authors concluded that convective therapies had no significant effect on reducing all‐cause mortality (RR 0.87), cardiovascular mortality (RR 0.75), and intradialytic hypotension (RR 0.72) but had uncertain effects on nonfatal cardiovascular

An alternative to the aggregated data meta‐analysis approach is to perform meta‐analysis of individual participant data in which the raw "individual level data" for each study are obtained and analyzed. The term "individual participant data" relates to the data recorded for each participant in a study. Individual participant data sets of four randomized trials were pooled and used to compare online HDF to HD. The four studies aggregated 2793 patients and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. HRs comparing the effect of online HDF versus HD on all‐ cause and cause‐specific mortality were calculated using Cox proportional hazard regression

In the first part of this individual participant data meta‐analysis, Davenport et al. [72] analyzed the relationship between convection volume and patient outcomes. After a median follow‐up time of 2.5 years, 769 of the 2793 participants had died (292 cardiovascular deaths). Convection

ities could not be confirmed.

92 Advances in Hemodiafiltration

0.49) and reduced serum β2M levels (‐5.95 mg/L).

to HD (RR 0.8 and 0.73, respectively).

events (RR 1.14) and hospitalization (RR 1.21).

*5.2.4. Individual participant data meta‐analysis*

models.

Online HDF can no longer be considered an experimental treatment; it is a mature RRT that is applied daily to sustain the lives of more than 160,000 ESKD patients worldwide, including 80,000 in Europe, Middle East, and Africa. Europe has played a leading role in developing this therapy, where the prevalence of HDF is close to 18% with variations across countries from 0 to 100%.

Interestingly, it has recently been also shown that clinical benefits associated with HDF were directly correlated with the total ultrafiltered volume delivered, either per session or per week. This finding adds a new component, namely convective dose, that needs to be integrated into our conventional dialysis adequacy concept. In addition, accumulating evidence from both retrospective and prospective RCT studies confirm the clinical safety and sustainability of HDF therapy and support its superiority over conventional HD in terms of morbidity and mortality.

In line with these facts, the remaining and crucial challenges today are to implement best clinical practices to achieve the optimal convective dose required, to define which subset of ESKD patients should benefit most, and to evaluate new tools facilitating and fine‐tuning HDF prescription according to ESKD patient needs (e.g., electrolyte balancing and quantification and homeostasis).
