Low Testosterone Accelerates Age-Associated Declines in Kidney Function Assessed Via Estimated Glomerular Filtration Rate in Men

Kidney function declines with increasing age and more than 50% of seniors over the age of 75 years are believed to have overt kidney disease. Data regarding declines in kidney function around the age of menopause in women are consistent with what would be expected of age alone, suggesting that the loss of estrogens do not contribute to declines in kidney function. In contrast, reports indicate that androgen deprivation therapy reduces estimated glomerular filtration rate (eGFR) and increases the risk of acute kidney injury, highlighting a possible influence of testosterone (T) on kidney function. The influence of age-related declines in T on declines in kidney function in otherwise healthy aging men has yet to be determine. PURPOSE: To determine the influence of low T on age-related declines in eGFR in men. Methods: Healthy young (YM; 18-40 years) and middle-aged/older (MA/O; 50-75 years) men participated. MA/O men were categorized as having either low (<300 ng/dL) or normal (400-1000 ng/dL) T via a venous blood draw. Serum creatinine and blood urea nitrogen (BUN) were quantified and eGFR was calculated using the 2021 CKD-EPI creatinine equation. Differences in eGFR and BUN were examined using the Kruskal-Wallis test with Dunn’s multiple comparisons test in the case of a significant main effect. Results: 23 YM (age: 29±4 y, T: 508±60 ng/dL), 23 MA/O men with low T (age: 59±7 y, T: 267±44 ng/dL), and 58 MA/O men with normal T (age: 58±6 y, T: 480±72 ng/dL) participated. Serum creatinine was significantly higher in MA/O men with low T (1.05±0.12 mg/dL) compared to YM (0.95±0.14 mg/dL, p=0.043) and MA/O men with normal T (0.96±0.11 mg/d, p=0.019). There were no differences between YM and MA/O men with normal T (p=0.956). There were significant age-associated declines in eGFR (YM= 109.9±14.3 vs. MA/O men with normal T= 90.1±9.3 mL/min/1.73m2, p<0.001) that were exaggerated in MA/O men with low T (82.6±10.4 mL/min/1.73m2, p=0.044 vs. MA/O men with normal T). BUN was significantly higher in MA/O men (normal T=17.2±3.4 mg/dL, low T=19.2 mg/dL) compared to YM (15.1±3.7 mg/dL, p=0.033 vs. normal T and p<0.001 vs. low T), but there was no difference between MA/O men with normal or low T (p=0.110). CONCLUSIONS: These data suggest that age-associated declines in testosterone contribute to declines in kidney function in otherwise healthy men. These data contrast evidence in women suggesting that the loss of estrogen during the menopause transition does not accelerate kidney dysfunction, suggesting sex differences in the mechanisms of kidney dysfunction. This work was supported by NIH grants R01AG049762, K01HL164978, U54A062319, T32AG000279, the Colorado Clinical and Translational Sciences Institute UL1TR001082, Colorado Nutrition and Obesity Research Center P30DK048520, and the Eastern Colorado GRECC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.