THE RELATIONSHIP BETWEEN ENZYMURIA AND KIDNEY ENZYME-ACTIVITIES IN EXPERIMENTAL GENTAMICIN-NEPHROTOXICITY

The aim of this study was to investigate the relationship between the urine excretion and kidney activities of enzymes predominantly located in the proximal renal tubule, viz. the lysosomal hydrolase N-acetyl-b eta-D-glucosaminidase (NAG) and the predominantly brush border enzymes alanine aminopeptidase (AAP) and gamma-glutamyltransferase (GGT) in a n experimental model of gentamicin nephrotoxicity. Groups of six anima ls received either gentamicin (50 mg/kg/day by intraperitoneal injecti on) or saline daily and were killed after 4, 7, 10, or 14 days of trea tment. Gentamicin nephrotoxicity was characterized by reduced creatini ne clearance rates and increased urinary flow rate and glycosuria, but only on day 14. Structural changes included a similar degree of vacuo lation of the renal proximal convoluted tubules (PCT) in all animals s acrificed on days 11 and 14, some evidence of PCT brush border loss, a nd the presence of protein casts on day 14. Following gentamicin treat ment, increased NAG, AAP, and GGT enzymuria were noted at all time poi nts tested. However while the increases in urine AAP and GGT activity were paralleled by decreased total renal activity, total kidney NAG ac tivity increased on days 4, 7,and 11 before falling back to pretreatme nt values on day 14. Interestingly, NAG enzymuria was highest in those animals with protein casts in the lumen of the PCT. The results sugge st that increased AAP and GGT enzymuria reflect loss of brush border i ntegrity while increased NAG enzymuria is consistent with the autophag ic response of the kidney to acute injury.