Effects of verapamil in the prevention of warm ischaemia induced acute renal failure in dogs

Acute renal failure in the immediate postoperative period remains a significant complication of renal transplantation. A major factor in the pathogenesis may be warm ischaemia (WI). Recent evidence implicates a calcium mediated mechanism as a final common pathway in certain models of acute renal failure. This study was undertaken to evaluate the effects of Verapamil, a calcium antagonist, in the prevention of warm ischaemiainduced acute renal failure following renal autotransplantation in the dog. Twenty‐one mongrel dogs were randomly allocated to three groups. Group 1 (control, 8 dogs) received 20 ml normal saline before a standardized 60 min warm ischaemic insult to the left kidney. Group 2 (6 dogs) received Verapamil (0.3 mg/kg) by intravenous injection and Group 3 (7 dogs) received Verapamil (0.3 mg/kg) by intra‐arterial injection into the left renal artery prior to the same ischaemic insult. The left kidney was heterotopically grafted to the right iliac fossa in the warm ischaemic period. Contralateral nephrectomy was performed. The dogs were followed up to 7 days after operation by serial creatinine estimation. Histological examination of some autografts was performed. Of the eight controls, six showed marked renal impairment (serum creatinine greater than 800, or death in renal failure). Three of the six dogs given intravenous Verapamil showed marked renal impairment. None of the seven dogs receiving intra‐arterial Verapamil showed marked renal impairment (P= 0.013, χ² test). The mean rate of serum creatinine rise for each group was analysed by multivariate analyses of variance. There was a significant reduction in the rate of creatinine rise in the intra‐arterial group (P= 0.03). There was a significant association (Spearman rank correlation, P= 0.005) between the creatinine levels and the severity of histological damage. It is concluded that intra‐arterial administration of Verapamil prior to warm ischaemic insult reduced the incidence of marked renal failure and rate of post ischaemia serum creatinine rise.