URINARY PI-CLASS GLUTATHIONE TRANSFERASE AS AN INDICATOR OF TUBULAR DAMAGE IN THE HUMAN KIDNEY

Glutathione transferase-pi released from kidney tubular epithelial cells was analyzed in the urine of recipients of renal allografts. Urinary content of alpha-class glutathione transferase was also determined for comparison. Control urine from healthy individuals contained detectable levels of the pi-isoenzyme (6.6 +/- 0.46 ng/ml, mean +/- SEM) and this concentration was not increased in the urine of patients demonstrating cyclosporine A-induced nephrotoxicity (6.3 +/- 0.29 ng/ml), in contrast to the alpha-form. Acute rejection increased excretion of the pi-isoenzyme (19.0 +/- 2.0 ng/ml), but not of the alpha-glutathione transferase. Thus, while the serum creatinine level increases in connection with both cyclosporine A-induced nephrotoxicity and acute rejection, analyses of urinary glutathione transferases distinguish well between these conditions. Acute tubular necrosis and renal transplant infarction resulted in a rapid elevation in urinary levels of both alpha- and pi-transferase. The advantages of this approach are that release of the protein into the urine occurs rapidly after tubular damage, the assay is sensitive and specific and can also distinguish between certain pathological conditions. These studies thus indicate that the urinary level of glutathione transferase-pi can be used for monitoring certain pathological processes in the kidney. Quantitation of this enzyme complements the information obtained by measurement of glutathione transferase-alpha.