Sex Hormones and Measures of Kidney Function in the Diabetes Prevention Program Outcomes Study

Context: Despite sex differences in chronic kidney disease (CKD) onset and progression, it is unclear whether endogenous sex hormones are associated with kidney function in persons without CKD. Design and Methods: We conducted a secondary analysis of the Diabetes Prevention Program (DPP) and its follow-up observational study, the DPP Outcomes Study, over 11 years. Participants included overweight and glucose-intolerant men (n = 889) and pre- and postmenopausal women (n = 1281) not using exogenous sex hormones and whose urine albumin-to-creatinine ratio (ACR) was <30 mg/g and normal estimated glomerular filtration ratio (eGFR) was >= 60 mL/min/1.73 m(2) at randomization. We examined the association between sex hormone levels and incidence of low eGFR and/or ACR >= 30 mg/g on at least one measurement. Results: At randomization, the mean (SD) eGFR was 94 (15) mL/min/1.73 m(2); the median ACR (interquartile range) was 4.5 (3.3 to 7.6) mg/g. During follow-up, 187 men (24.6%) and 263 women (24.2%) had incident albuminuria and 136 men (17.9%) and 123 women (11.3%) had incident low eGFR. Among men, higher baseline sex hormone-binding globulin (SHBG) level was associated with reduced low eGFR risk (hazard ratio per SD, 0.80; 95% CI, 0.57 to 0.90) in adjusted analyses. No significant associations were observed among women. There were significant interactions between sex steroid levels and low eGFR by randomization arm. Conclusion: Sex steroids were not associated with development of low eGFR or albuminuria. Among men, higher SHBG level was associated with reduced risk of low eGFR on at least one measurement.