Sex Differences in Associations Between Measures of Hemodialysis Adequacy and Quality, Cardiovascular Outcomes, and Mortality: A Systematic Review

Rationale & Objective The female survival advantage is diminished with hemodialysis. We evaluated the associations between measures of hemodialysis adequacy and quality and cardiovascular outcomes and mortality by sex. Study Design Systematic review of randomized controlled trials (RCTs) and observational studies. Electronic databases (Medline, EMBASE, CENTRAL) were searched from inception to August 01, 2024. Setting & Study Populations Adults living with kidney failure treated with maintenance hemodialysis, stratified by sex. Selection Criteria for Studies Studies comparing measures of higher versus lower hemodialysis adequacy and quality (Kt/V, urea reduction ratio (URR), ultrafiltration rate (UFR), treatment time) as exposures and reporting mortality (cardiovascular-related, all-cause), major adverse cardiovascular events or cardiovascular-related hospitalization as outcomes. Data Extraction Data were extracted independently in duplicate. Analytical Approach Results were synthesized following Synthesis Without Meta-analysis reporting guidelines. Results Thirty-one studies (n=1,402,002 participants) reported results by sex; only 10 studies reported the interaction by sex. Multiple measures of adequacy with varying definitions of “higher” and “lower” were reported with Kt/V being the most common. Three studies reported a greater decrease in all-cause mortality in females compared to males with higher spKt/V; one study reported no difference by sex. One study reported a greater decrease in all-cause mortality in females compared to males with higher URR; one study reported no difference by sex. One study reported a greater decrease in all-cause mortality in females compared to males with greater weekly hemodialysis treatment time; one study reported no difference by sex. Two studies reported greater all-cause mortality with higher UFR in females compared to males. Limitations Inconsistent reporting of hemodialysis adequacy and quality measures. Inconsistent inclusion of factors known to impact important clinical outcomes. Conclusions While results should be interpreted with caution due to significant study heterogeneity, females may derive greater benefit with higher measures of hemodialysis adequacy and quality compared to males.