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

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/1.73m 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/1.73m 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/1.73m per year) than in women (-1.79; 95% CI, -1.92 to-1.66mL/min/1.73m 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.