NEPHROTOXICITY OF CEPHALORIDINE IN NEWBORN RABBITS - ROLE OF RENAL ANIONIC TRANSPORT-SYSTEM

Abstract

The nephrotoxicity of cephaloridine [a wide spectrum antibiotic used i.m. for a variety of bacterial infections], cefazolin and mercuric chloride was studied in rabbits of various ages. Cephaloridine produced dose-related elevations in serum urea N, creatinine and renal tubular necrosis in adult and 30-day-old rabbits, only slight changes at 15 days of age and no effect in 5-day-old rabbits. Cefazolin also produced dose-related nephrotoxicity in adult rabbits but no effect in 15-day-old rabbits. Mercuric chloride administration resulted in similar nephrotoxicity in 5-, 15- and 30-day-old rabbits and adults. The development of susceptibility to cephaloridine nephrotoxicity paralleled the maturation of the renal anionic transport system as determined by the accumulation of p-aminohippurate by renal cortical slices in vitro. Substrate stimulation of the anionic transport system by p-aminohippurate or penicillin increased the nephrotoxicity of cephaloridine in newborn rabbits. Lack of cephaloridine nephrotoxicity in newborn rabbits is apparently due to the incomplete development of the renal anionic transport system.