The Renal Iohexol Clearance Survey examined whether testosterone is a risk factor for age-related measured glomerular filtration rate decline in males.

INTRODUCTION

Testosterone has been hypothesized to contribute to glomerular filtration rate (GFR) decline in males through its effects on kidney cells and the renin-angiotensin system. However, prior research relied on creatinine-based estimated GFR (eGFR), which may be biased by the association between testosterone and muscle mass, as increased muscle mass raises serum creatinine independently of true GFR. Here, we investigate the association between serum levels of total testosterone (TT), free testosterone (FT), and sex hormone-binding globulin (SHBG) and age-related decline in measured GFR (mGFR).

METHODS

We included a representative sample of 800 males aged 50-62 years old from the general population without self-reported cardiovascular disease, diabetes, or kidney disease. All participants underwent plasma iohexol clearance measurements between 2007-2009, with follow-ups in 2013-2015 (656 individuals) and 2018-2020 (578 individuals). The association of FT, TT, and SHBG with mGFR decline and accelerated mGFR decline, defined as the 10% with the steepest GFR decline (-1.64 mL/min per 1.73 m2 or more per year), was assessed using linear mixed models and logistic regression.

RESULTS

Both TT and SHBG were associated with a higher mGFR at baseline (0.27 ml/min/1.73 m2 [95% confidence interval: 0.09-0.45] per 1 nmol/L higher TT and 0.79 ml/min per 1.73 m2 [0.18- 1.41] per 10 nmol/L higher SHBG). Neither TT, FT, nor SHBG were associated with mGFR decline in the multivariable-adjusted linear mixed model analyses (-0.02 [-0.04 to 0.01] and -0.03 [-0.15 to 0.08] ml/min per 1.73 m2 per year for each nmol/L increase in TT and FT, respectively, and -0.04 [-0.12 to 0.05] ml/min per 1.73 m2 per year for each 10 nmol/L increase in SHBG).

CONCLUSION

Testosterone was not associated with age-related GFR decline in males aged 50 to 62 years at baseline in the general population over a median follow-up of 10.9 years.