Effect of Diazepam Premedication on Acute Kidney Injury Due to Ischemia-Reperfusion in Rats

Background: Ischemia-reperfusion injury (IRI) impairs kidney transplants. Diazepam can reduce IRI through peripheral benzodiazepine receptors. We aimed to evaluate the effect of diazepam premedication on the IRI of the rat kidney. Methods: Fourteen days after unilateral nephrectomy, male Sprague-Dawley rats underwent a 45 min sole kidney ischemia. Sixty minutes prior to ischemia, the animals were randomly assigned to a subcutaneous injection of 0.75 mg diazepam (n = 28) or 0.5 mL 0.9% NaCl (n = 31). Results: After 48 h, serum creatinine of diazepam-administered rats was lower and creatinine clearance was higher than in controls (119.8 ± 73.3 vs. 217.5 ± 105.3 µmol/L, p < 0.01 and 0.14 ± 0.07 vs. 0.08 ± 0.05 mL/min/100 g BM, p < 0.01, respectively). Moreover, the former had lower urinary losses of sodium and potassium (fractional excretions of 1.24 ± 1.39% vs. 2.87 ± 3.66%, p = 0.02 and 111.1 ± 95.7% vs. 199.0 ± 143.3%, p < 0.01, respectively). After 7 days, diazepam-treated rats remained superior vs. controls, regarding serum creatinine (53.7 ± 12.7 vs. 77.6 ± 21.3 µmol/L, p < 0.01), creatinine clearance (0.22 ± 0.08 vs. 0.17 ± 0.06 mL/min/100 g BM, p < 0.01), potassium sparing (50.2 ± 31.7% vs. 73.4 ± 38.7% excretion, p < 0.01), and renal edema (1.92 ± 0.45 vs. 2.30 ± 0.61 g of kidney mass, p < 0.01). Furthermore, their 24 h proteinuria was marginally reduced (4.03 ± 2.62 vs. 5.06 ± 2.74 mg, p = 0.06). Conclusions: Administration of diazepam preceding renal ischemia attenuates subsequent kidney injury in rats. Benzodiazepines may be beneficial prior to kidney transplantation.