Association of sex with all-cause and cause-specific peritoneal dialysis discontinuation

Rationale & Objective: Little is known about the association between sex and specific causes of peritoneal dialysis (PD) discontinuation. This study assessed the association of sex with all-cause and cause-specific PD discontinuation and explored the factors mediating these relationships. Study Design: Retrospective cohort study. Setting & Participants: All patients with kidney failure who started PD between 2005 and 2019 in Australia. Exposure: Sex. Outcome: All-cause (transfer to hemodialysis for ≥30 days or death) PD discontinuation, PD discontinuation related to inadequate dialysis, and PD discontinuation related to infection. Analytical Approach: Adjusted cause-specific proportional hazards regression models were used to assess the association of sex with all-cause and cause-specific PD discontinuation. Counterfactual mediation analysis was conducted to explore potential mediators (sociodemographic status, geographical remoteness, cardiovascular disease, diabetes, history of peritonitis, late referral, smoking status, and body mass index) of these associations. Sensitivity analyses using the Fine and Gray method were implemented to address the competing risks of death, kidney transplantation, and other causes of PD discontinuation. Results: Of 9,748 incident patients, 6,001 experienced PD discontinuation from any cause (2,098 died, 793 were inadequate dialysis related, 1,442 were infection related, and 1,668 were other cause), with a median follow-up of 1.47 years (IQR, 0.67-2.73). Men were more likely to experience PD discontinuation from any cause (HR, 1.09 [95% CI, 1.03-1.14], P = 0.002) or for inadequate dialysis (HR, 1.71[95% CI, 1.47-1.99], P < 0.001) but not for infection (HR, 0.95[95% CI, 0.85-1.05], P = 0.3). The mediation analyses found that 76.9% of the total effect of sex on all-cause PD discontinuation was explained by mediators, including cardiovascular disease, smoking status, and diabetes, whereas less than 10% of the total effect of sex on PD discontinuation from inadequate dialysis was explained by mediators. Limitations: Residual and unmeasured confounders, such as biological differences, behavioral patterns, hospitalizations, frailty, and severity of comorbidities. Conclusions: Men were more likely than women to experience PD discontinuation from any cause and from inadequate dialysis. This relationship was mediated by multiple morbidities for PD discontinuation from any cause but not for PD discontinuation for inadequate dialysis. These findings may inform future studies evaluating biological and sociodemographic factors that may contribute to these observed sex differences. Plain-Language Summary: Sex and gender differences can influence kidney disease risk, progression, access to care, and outcomes. However, their role in peritoneal dialysis (PD) discontinuation is not well understood. We studied the association between sex and PD discontinuation in Australian patients with kidney failure from 2005 to 2019, and whether sociodemographic factors and comorbidities influenced this relationship. We found that men were more likely to discontinue PD overall and because of inadequate dialysis but not because of infectious complications. Cardiovascular disease, smoking, and diabetes explained most of the differences between men and women for all-cause PD discontinuation but not for discontinuation due to inadequate dialysis. These findings may inform future studies evaluating biological and sociodemographic factors that may contribute to these observed sex differences.