Sex Differences in the Progression of CKD Among Older Patients: Pooled Analysis or 4 Cohort Studies

Rationale & Objectives: Data for the association of sex with chronic kidney disease (CKD) progression are conflicting, a relationship this study sought to examine. Study Design: Pooled analysis of 4 Italian observational cohort studies. Setting & Participants: 1,311 older men and 1,024 older women with estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m(2) followed up in renal clinics. Predictor: Sex. Outcomes: End-stage kidney disease (ESKD), defined as maintenance dialysis or kidney transplantation, as the primary outcome; all-cause mortality and eGFR decline as secondary outcomes. Analytical Approach: Cox proportional hazard analysis to estimate the relative risk for ESKD and mortality and linear mixed models to estimate the rate of eGFR decline. Results: Age, systolic blood pressure, and use of renin-angiotensin system inhibitors were similar in men and women. Baseline eGFRs were 27.6 +/- 10.2 in men and 26.0 +/- 10.6 mL/min/ 1.73 m(2) in women (P < 0.001), while median proteinuria was lower in women (protein excretion, 0.45 [IQR, 0.14-1.10] g/d) compared with men (0.69 [IQR 0.19-1.60] g/d; P < 0.001). During a median follow-up of 4.2 years, 757 developed ESKD (59.4% men) and 471 died (58.4% men). The adjusted risks for ESKD and mortality were higher in men (HRs of 1.50 [95% CI, 1.28-1.771 and 1.30 [95% CI, 1.06-1.601, respectively). This finding was consistent across CKD stages. We observed a significant interaction between sex and proteinuria, with the risk for ESKD in men being significantly greater than for women at a level of proteinuria of similar to 0.5 g/d or greater. The slope of decline in eGFR was steeper in men (-2.09; 95% CI, -2.21 to -1.97 mL/min/1.73 m(2) per year) than in women (-1.79; 95% CI, -1.92 to -1.66 mL/min/1.73 m(2) per year; P < 0.001). Although sex differences in eGFR decline were not different across CKD stages (P = 0.3), the difference in slopes between men and women was progressively larger with proteinuria > 0.5 g/d (P = 0.04). Limitations: Residual confounding; only whites were included. Conclusions: Excess renal risk in men may, at least in part, be related to higher levels of proteinuria in men compared with women.