An investigation of cyclosporine A (CyA) nephrotoxicity by lithium clearance

Abstract

It has been widely recognized that cyclosporine A (CyA) is useful in transplantation of the kidneys. On the other hand, the nephrotoxicity as one of its adverse effects is clinically important. There have been accumulated pieces of pathological evidence that CyA causes the renal proximal tubule damage. However, there are few reports available on the changes in the proximal tubular function. Recently, lithium clearance (CLi) has been employed to assess the proximal tubular function in CyA nephrotoxicity, because lithium ions are mainly reabsorbed throughout the proximal tubules in the same proportion as sodium and water. Several studies have already shown that long-term CyA administration results in a decrease in CLi reflecting enhanced lithium ion reabsorption. I studied, in male Sprague-Dawley rats, 1) whether short term and small dose of CyA administration which does not induce the renal tubular cell damage affects CLi and 2) the possibility that high salt intake influences CLi in CyA nephrotoxicity. Then, I divided rats into 6 groups: three groups were allowed the access to water, but the other three groups of rats were allowed to drink only saline. Group 2 and 3 were received 12.5 mg/kg and 25 mg/kg, respectively, of CyA intraperitoneally every day. As for creatinine clearance (Ccr), Ccr of group 3 (CyA 25) was the lowest, being significantly different from the other two groups. The most important result is fractional reabsorption of sodium and water in the proximal tubule. There is a significant difference between 1-A (vehicle, H2O) and 2-A (CyA 12.5, H2O), but no significant difference between 1-B (vehicle, saline) and 2-B (CyA 12.5, saline).(ABSTRACT TRUNCATED AT 250 WORDS)