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

Abstract

Rationale & objective: 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)<45mL/min/1.73m² 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±10.6mL/min/1.73m² 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, 1.28-1.77] and 1.30 [95% CI, 1.06-1.60], 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 ∼0.5g/d or greater. The slope of decline in eGFR was steeper in men (-2.09; 95% CI, -2.21 to-1.97mL/min/1.73m² per year) than in women (-1.79; 95% CI, -1.92 to-1.66mL/min/1.73m² 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 >0.5g/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.

Keywords: Chronic kidney disease (CKD); eGFR decline; end-stage kidney disease (ESKD); epidemiology; estimated glomerular filtration rate (eGFR); older adults; outcomes; proteinuria; renal disease progression; sex; sex differences.