Lack of Testosterone (TST) Worsens Ischemia/Reperfusion– Induced Acute Kidney Injury (I/R‐AKI) and its Deleterious Cardiac Effects

Abstract

Renal I/R‐AKI results in systemic inflammation, including the heart. We recently reported that plasma TST is reduced during AKI, and its supplementation improves renal injury and inflammation by increasing cytoprotective factors. We now extended this study to test whether the lack of TST exacerbates I/R‐AKI and its cardiac abnormalities. Intact and castrated males (Cast) SD rats were treated with either vehicle or TST (20 ng/kg/min × 10min IV) given 3 hours after subjecting the rats to 40 min of bilateral renal I/R. After 48 hs, we harvested the kidney and the heart, and evaluated renal function and injury (PlCr ‐KIM‐1), cardiac stress (pro‐BNP), and cytoprotective factors (renal and cardiac heme oxygenase‐ HO‐1). PlCr mg/dl KIM‐1 pg/ml BNP ng/ug Renal HO‐1 ng/ml Cardiac HO‐1 ng/ml Sham 0.4 ±0.3 712 ±53 0.18 ±0.02 0.52±0.4 0.4 ±0.06 AKI 1.9 ±1.9* 4576 ±185* 3.8 ±0.1* 5.8±1.2* 5 ±0.1* AKI‐Cast 2.5 ±2.3& 8972 ±708& 4.4 ±1& 3±0.1& 3.7 ±0.1& AKI‐Cast‐TST 1.6 ±1# 2348 ±85 # 2.4 ±0.6# 4.4±0.2# 4.6 ±0.1# Data: Mean±SEM: p<0.05 vs Sham; vs AKI; vs AKI‐CT Lack of TST exacerbates I/R‐AKI and cardiac stress. Despite the increased injury, HO‐1 is decreased, suggesting that TST may be facilitating HO‐1 expression post AKI.