Urinary Enzymes as Indicators of Aminoglycoside Nephrotoxicity

František Trejtnar (trejtfr@faf.cuni.cz),

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Hradec Králové

Summary

An optimalized methodical arrangement for testing of enzymuria in rats was used in this study to asses the diagnostic value of urinary excretion of selected enzymes with different localization in renal tubules for detection of gentamicin-induced kidney damage. For this purpose, changes of excretion of two brush border enzymes, alaninaminopeptidase (AAP) and gamma-glutamyl-transferase (GGT), and a lysosomal enzyme, N-acetyl-beta-D-glucosaminidase (NAG), were studied during eight-day administration of gentamicine in nephrotoxic doses (40 and 80 mg/kg/day). The rate of enzymuria was compared to changes of other parameters of renal function such as creatinine and urea excretion. The increase of urinary excretion of AAP and GGT was characterized by a rapid appearance (the 2nd day after the start of treatment) and not distinct gradation with continuing nephrotoxine administration. Excretion of lysosomal NAG was clearly dose-dependent and was marked by a progressive rise up to the end of treatment indicating cummulative intensification of renal damage. Elevated enzymuria indicated gentamicine-induced dysfunction with a greater sensitivity than impairment of creatinine or urea excretion. A normalization of increased AAP and GGT excretion after higher dosage of gentamicin was preceded by a marked decrease below control values. This finding could give evidence for a limited character of enzyme sources and their subsequent exhaustion by excessive washing into urine during previous damage to tubular cells. Determination of excretion values of all of studied urinary enzymes can be used as an early marker of acute tubulotoxicity. NAG is the best indicator of the development of aminoglycoside renal damage.