Testosterone supplements exacerbate renal injury in hypertensive rats with reduced renal mass

Abstract

Men with end-stage renal disease are frequently given androgen supplements to improve sexual function. We have previously shown that endogenous androgens contribute to hypertension and renal injury in various animal models. We hypothesized that testosterone supplements exacerbate hypertension and renal injury in rats with reduced renal mass (RRM). Sprague Dawley rats were subjected to surgical ablation of 80% of the renal mass or left intact. The rats were then given 8% NaCl diet for 6 weeks. Testosterone was administered in Silastic pellets throughout the study to groups of rats with intact or ablated kidneys. Arterial pressure was continuously monitored by telemetry. Renal injury was assessed by measurements of urinary protein and neutrophil gelatinase-associated lipocalin (NGAL) excretion. RRM developed hypertension on the high salt diet as compared with intact rats (154±12 vs 111±3mmHg). Testosterone supplementation did not alter the course of hypertension in RRM, nor increased blood pressure in intact rats (156±12 vs 113±8mmHg, RRM vs intact). Starting at week 2 until the end of the study, testosterone-supplemented RRM consistently excreted 20 to 30% more protein than untreated RRM. Urinary levels of NGAL, an index of tubulointerstitial injury, were also higher in RRM as compared to intact rats and were further augmented by testosterone supplements. Our data indicate that testosterone supplements worsen renal injury in a model of chronic hypertensive renal disease without affecting blood pressure.