Value of enzyme determinations in urine for the diagnosis of nephrotoxicity in rats

Excretion of urinary lactate dehydrogenase (LDH, EC 1.1.1.27), gamma-glutamyltransferase (gamma-GT, EC 2.3.2.2), alkaline phosphatase (ALP, EC 3.1.3.1), alanine aminopeptidase (AAP, EC 3.4.11.-), alanine aminotransferase (GPT, EC 2.6.1.2) and N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) was studied following a single i.v. application of 1 mg mercuric chloride/kg body weight or a radio contrast medium (SH H 340 AB) at a dose of 7.5 g iodine/kg body weight in rats. Measurements of urinary enzymes and serum urea nitrogen and creatinine were carried out on the second, third, fourth and ninth days after treatment. Histological examinations of kidneys were performed on day 9. A drastic increase in urinary LDH and moderate increase in gamma-GT, ALP and AAP and a very slight increase in GPT was observed in the first 18-h urine samples after mercuric chloride. This increase in enzymuria was associated with a drastic increase in serum urea nitrogen and creatinine, with a maximum on day 4. The radio contrast medium-treated animals showed a similar but less pronounced pattern of urinary enzymes excretion and only a slight increase of serum urea nitrogen on day 2. A good correlation was found between histological findings and enzymuria as well as serum urea nitrogen and creatinine. Thus, determination of only some urinary enzymes (LDH and gamma-GT) is valuable in predicting early nephrotoxicity and sufficient for the diagnosis of proximal tubule damage in rats.