Differentiation between acute cyclosporine nephrotoxicity and acute tubular necrosis using enalaprilat renal scintigraphy in rats.

Abstract

Acute cyclosporine (CsA) nephrotoxicity cannot be easily differentiated from other renal parenchymal complications, such as acute tubular necrosis (ATN), that cause renal function impairment at the early posttransplantation period. The purpose of this study was to differentiate acute CsA nephrotoxicity from ATN using enalaprilat renal scintigraphy in rats. Twenty-six rats were divided into 4 experimental groups: CsA group, who were treated with CsA (50 mg/kg/d) for 2 days; ATN group, who received clamping of both renal arteries for 45 minutes; vehicle group, who were treated with olive oil (1 mL/kg/d) for 2 days; and sham-operated group, who received the same surgical procedure as ATN group without clamping of renal arteries. The baseline study was performed with 300 microCi of technetium-99m diethylenetriaminepentaacetic acid and enalaprilat scintigraphy with 2 mCi of technetium-99m diethylenetriaminepentaacetic acid 5 minutes after intravenous enalaprilat injection (30 microg/kg). The changes of renogram grade and the renal function indices such as T(max), T(1/2), residual cortical activity, and mean transit time between 2 studies were analyzed. Immediately after renal scintigraphy, blood urea nitrogen and serum creatinine levels were measured and renal tissues stained by periodic acid Schiff reaction were examined in each group. Blood urea nitrogen and serum creatinine levels in the CsA and ATN groups were higher than their control groups (P < 0.05). Histologic study revealed severe ischemic necrosis of tubular epithelium in ATN group, but the other groups remained with essentially normal morphology. After enalaprilat injection, renal function indices became improved in CsA group, whereas they deteriorated in ATN group. The renogram grade was decreased in CsA group and increased or unchanged in ATN group after enalaprilat injection. The T(max), residual cortical activity, and mean transit time ratio were statistically different between the 2 groups on enalaprilat study (P < 0.05). These results suggest that enalaprilat renal scintigraphy could be used clinically in differentiating acute CsA nephrotoxicity from ATN after renal transplantation.