Naloxone in renal ischemia: a functional and microanatomical study.

Naloxone HCl (Nx) improves cardiopulmonary performance, reverses cellular hypoxia, and stabilizes lysosomal membranes in shock states. However, no detailed study has yet explored its potential role in renal ischemia, which is inevitable in transplantation and surgical and nonsurgical conditions associated with hypotension and shock. This functional and microanatomical study was carried out on dogs subjected to renal warm ischemia with contralateral nephrectomy. Group I (control; N = 4) had bilateral renal dissection and right nephrectomy. Groups II-IV had their kidney pedicles cross-clamped for 60 min and then reperfused. Group II (N = 9) ischemic kidneys received no treatment. Group III (N = 6) kidneys were flushed with pure Nx HCl (2 mg/kg) during ischemia. Group IV (N = 6) dogs received one iv Nx bolus (2 mg/kg) before clamping and another dose before declamping. Biopsies for adenine nucleotides, histology, and ultrastructure were obtained before ischemia, before reflow, and 15 min and 7 days after reflow. Serum creatinine and blood urea nitrogen were measured daily. Ischemia induced significant renal dysfunction, which was reversed by systemic Nx. Nx offered a remarkable protection against postischemic structural damage. Seventy percent of Group II cortical sections showed grade 4 acute tubular necrosis (ATN), and severe residual damage after a week. Eighty-three percent of Group IV sections showed grade 1 ATN and no residual damage after a week. One week survival was 33% in Group II and 100% in Group IV. Nx can be useful in prevention of acute renal failure in clinical situations with arterial hypotension and shock.