Hemodiafiltration Reduces Mortality Risk in Patients With ESRD

The rates of morbidity and mortality among patients with end-stage renal disease (ESRD) undergoing hemodialysis remain high. The leading cause of death in this patient population is cardiovascular disease, accounting for more than half of deaths with a known etiology (52.2%). One approach to improving the prognosis of patients receiving hemodialysis is the use of alternative hemodialysis modalities.

One such alternative is hemodiafiltration (HDF), a hybrid renal replacement therapy combining the principles of hemodialysis with hemofiltration. HDF provides the benefits of solute removal via blood diffusion and convection, resulting in more efficient clearance of medium and small molecular substances, compared to hemodialysis or hemofiltration alone.

Results of previous trials and meta-analyses comparing HDF to hemodialysis have resulted in contrasting findings. Yifan Zhu, MM, Juan Li, MM, and colleagues conducted a systematic review and meta-analysis to examine the most current and reliable data on the impact of HDF in patients with ESRD.

The researchers performed a systematic review of studies published in PubMed, EMBASE, and the Cochrane Library. Inclusion criteria were randomized controlled trial; study population ≥18 years of age; eligible patients receiving maintenance hemodialysis for at least three months, three times per week for a minimum of four hours each session; and patients receiving either hemodialysis or HDF. The search was conducted through January 14, 2024. Relevant data and evaluation of the quality of evidence were analyzed using Review Manager 5.3 software.

The analysis included data from 10 randomized controlled trials, representing a total of 4,654 patients. One study was conducted in South Korea and one in Turkey, and the remainder were conducted in Europe. The intervention group received HDF mode dialysis; seven used postdilution, two had an unknown dilution method, and one used predilution. Patients in the control group received hemodialysis; five used high-flux, three used low-flux, and the remaining two did not specify flux type.

The outcomes of interest included all-cause mortality (10 trials; 4,654 participants), cardiovascular mortality (six trials; 4,215 participants), sudden death (four trials; 2,783 participants), and infection-related mortality (three trials; 3,048 participants). Baseline data were generally evenly distributed across all trials.

Among the 10 studies that reported on all-cause mortality, 4,613 patients were followed for an average of 24 months. Of them, 21% (n=981) died from any cause. There was a significant reduction in mortality among patients in the intervention group compared to the control group (relative risk [RR], 0.84; 95% CI, 0.72-0.99; P=.04).

In the six trials reporting cardiovascular mortality, 9.2% of patients (n=383/4,141) died from cardiovascular causes during the follow-up period. In the four trials that reported sudden deaths, 3.9% (n=108/2,783) experienced sudden death. In the three trials that reported infection-related death, 5.0% (n=151/3,048) had an infection-related death.

There was a 26% reduction in cardiovascular mortality in the HDF group compared to the control group (95% CI, 0.61-0.90; P=.002). There were no statistically significant differences between the two groups in the incidence of sudden death (RR, 0.92; 95% CI, 0.64-1.34; P=.68) or infection-related mortality (RR, 0.70; 95% CI, 0.47-1.03; P=.07).

The researchers also performed subgroup analyses based on hemodialysis flux. Results revealed an association between HDF and a reduction in all-cause mortality and cardiovascular mortality when compared to high-flux hemodialysis (RR, 0.81; 95% CI, 0.69-0.96; P=.01 and RR, 0.76; 95% CI, 0.59-0.98; P=.04, respectively). There was no statistically significant difference in all-cause mortality between HDF and low-flux hemodialysis (RR, 0.93; 95% CI, 0.77-1.12; P=.44).

In results of subgroup analyses of all-cause mortality and cardiovascular mortality based on convection volume, there was an association between HDF with a convection volume of 22 L or greater and a reduction in both all-cause mortality and cardiovascular mortality (RR, 0.76; 95% CI, 0.65-0.88; P=.0002 and RR, 0.73; 95% CI, 0.57-0.94; P=.01, respectively). There was no statistically significant reduction in all-cause mortality (RR, 0.98; 95% CI, 0.66-1.47; P=.93) or cardiovascular mortality (RR, 0.76; 95% CI, 0.57-1.03; P=.08) with HDF with a convection volume less than 22 L.

The researchers cited some limitations to the findings, such as the study population including primarily individuals of European descent, possibly limiting the generalizability of the findings to other populations. In addition, the accuracy of the study conclusions may have been limited due to the inability to access individual-level data. Finally, the limited number of studies on sudden death and infection-related death may have had an impact on the precision of the conclusions drawn.

In summary, the authors said, “This meta-analysis suggests that hemodiafiltration leads to better outcomes for patients with end-stage renal disease, particularly a reduction in overall mortality and cardiovascular mortality. Notably, this benefit seems to be more pronounced for patients receiving HDF with a high convection volume.”

Source: BMC Nephrology.