Romanian Society of Pharmaceutical Sciences

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TESTOSTERONE SUPPLEMENTS ACCELERATE PROGRESSION OF KIDNEY INJURY IN A RAT MODEL OF REDUCED RENAL MASS

RADU ILIESCU1,2,*, MONICA HĂNCIANU3, JANE F. RECKELHOFF2

1.Department of Physiology, University of Medicine and Pharmacy “Gr. T. Popa” Iasi,16 Universitatii St., Iasi, Romania,
2.Department of Physiology, University of Mississippi Medical Center, 2500 North State St., Jackson, MS, USA
3.Faculty of Pharmacy, University of Medicine and Pharmacy “Gr. T. Popa” Iasi,16 Universitatii St., Iasi, Romania,

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Men with end-stage renal disease are frequently given androgen supplements to improve sexual function. 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). Rats subjected to surgical ablation of 80% of renal mass were 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 Sham rats (156±12 vs 113±8mmHg, RRM vs Sham). 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.