Cyclosporine and renal enzyme excretion

The measurement of enzyme activity in the urine provides a sensitive assessment of renal tubular cell damage. In addition, the presence of particular enzymes indicates both the subcellular origin and likely site of damage within the nephron. Cyclosporine (CsA) nephrotoxicity in the rat, characterized by reduced glomerular filtration rate and structural damage to the proximal renal tubule, is associated with elevated activities of the lysosomal hydrolase, N-acetyl-beta-D-glucosaminidase (NAG), in the urine. The degree of enzymuria is dose dependent, reversible on drug withdrawal and related to the severity of the histological damage. Moreover, increased enzymuria usually precedes both the reduction in renal function and the presence of structural abnormalities. The co-administration of other potentially nephrotoxic agents (e.g., gentamicin), the diuretic frusemide, or inhibitors or suppressors of hepatic drug metabolism increases the degree of NAG enzymuria, whilst inducers of drug metabolism (e.g., phenobarbitone) have the reverse effect. Urine levels of gamma-glutamyl transpeptidase (gamma GT) are also increased following CsA administration indicating an injurious effect on the brush border of the renal tubule.