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

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.

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 m2 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.

At randomization, the mean (SD) eGFR was 94 (15) mL/min/1.73 m2; 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.

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.