Associations of endogenous androgens and sex hormone-binding globulin with kidney function and chronic kidney disease

INTRODUCTION: The role of endogenous androgens in kidney function and disease has not been extensively explored in men and women.

RESEARCH DESIGN AND METHODS: We analyzed data from the observational KORA F4 study and its follow-up examination KORA FF4 (median follow-up time 6.5 years) including 1293 men and 650 peri- and postmenopausal women, not using exogenous sex hormones. We examined the associations between endogenous androgens (testosterone [T], dihydrotestosterone [DHT], free T [fT], free DHT [fDHT], and T/DHT), with estimated glomerular filtration rate (eGFR) at baseline and follow-up, prevalent, and incident chronic kidney disease (CKD) adjusting for common CKD risk factors.

RESULTS: At baseline, 73 men (5.7%) and 54 women (8.4%) had prevalent CKD. Cross-sectionally, no significant associations between androgens and kidney function were observed among men. In women, elevated T (β=-1.305, [95% CI -2.290; -0.320]) and fT (β=-1.423, [95% CI -2.449; -0.397]) were associated with lower eGFR. Prospectively, 81 men (8.8%) and 60 women (15.2%) developed incident CKD. In women, a reverse J-shaped associations was observed between DHT and incident CKD (Pnon-linear=0.029), while higher fDHT was associated with lower incident CKD risk (odds ratio per 1 standard deviation=0.613, [95% CI 0.369; 0.971]. Among men, T/DHT (β=-0.819, [95% CI -1.413; -0.226]) and SHBG (Pnon-linear=0.011) were associated with eGFR at follow-up but not with incident CKD. Some associations appeared to be modified by type 2 diabetes (T2D).

CONCLUSION: Suggestive associations are observed of androgens and SHBG with kidney impairment among men and women. However, larger well-phenotyped prospective studies are required to further elucidate the potential of androgens, SHBG, and T2D as modifiable risk factors for kidney function and CKD.