The hidden interplay between sex and adverse outcomes in incident dialysis patients: The role of aortic calcification

Background: Research on the sex disparity in the prognosis of chronic kidney disease (CKD), particularly among those who are newly initiating dialysis, is limited and inconclusive. This study aimed to investigate the associations between sex, and all-cause mortality and major cardiovascular adverse events (MACE), with a particular focus on the presence of aortic calcification (AC). Methods: We conducted a post hoc analysis of 1459 incident dialysis patients included in this prospective cohort study. The primary outcome of interest was all-cause mortality, and the secondary endpoint was a composite of MACE. Results: During a median follow-up period of 3.55 years, 362 (269 male and 93 female) patients died and 477 (342 male and 135 female) patients developed MACE. The risks for all-cause mortality [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.47-0.79] and MACE (HR 0.74, 95% CI 0.60-0.93) were lower in females than in males. This finding was robust across multiple sensitivity analyses and most subgroups. Moreover, the associations between sex and adverse outcomes were significantly modified by AC status at dialysis initiation (P for interaction <.05). Specifically, among patients without AC, females exhibited lower risks for all-cause mortality (HR 0.45, 95% CI 0.29-0.69; P <. 001) and MACE (HR 0.67, 95% CI 0.49-0.93; P =. 015), whereas no differences were observed for all-cause mortality (HR 0.82, 95% CI 0.59-1.15; P =. 256) or MACE (HR 0.80, 95% CI 0.59-1.10; P =. 174) among patients with AC. Conclusions: In patients with renal failure receiving dialysis, AC abolished the survival and cardiovascular protection observed in female versus male patients. This finding supports the need for greater awareness of the AC burden in female dialysis patients.