Urinary Excretion of Three Specific Renal Tubular Enzymes in Patients Treated with Nonsteroidal Anti-Inflammatory Drugs (NSAID)

Abstract

Ten patients, mean age 51.50 ± 3.03 years, with degenerative rheumatism on NSAID treatment without any sign of renal desease, and 11 control subjects, mean age 43.50 ± 1.51 years, were studied. NSAID treatment was of 11.30 ± 5.60 weeks duration in average, with ibuprofen, naproxen, or indomethacin. Urinary excretion of three specific renal tubular enzymes—AAP: alanine-amino-peptidase, GGT: γ-glutamyl-transpeptidase, and β-NAG: β-N-acetyl-glucosaminidase, were determined in 8-h overnight urine samples, as well as GFR creatinine clearancel 1.73 m², urinary volume/8 h, specific gravity of the urine, proteinuria and glucosuria. In the group treated with NSAIDs, urinary excretion of the enzymes was significantly higher than in the control group—AAP: 1414.20 ± 317.60, 864.20 ± 94.42, p < 0.00001; GGT: 8034.6 ± 1378.55, 5095.64 ± 614.40, p < 0.00001, and β-NAG: 1644.60 ± 299.97, 964.82 ± 142.00, p < 0.00001. Patients on NSAID treatment showed abnormal urinary excretion of AAP in 7/10 cases, of GGT in 6/10, and of β-NAG in 7/10 cases. Duration of the treatment did not correlate with the urinary excretion of the enzymes. Age was in correlation with the urinary excretion of the enzymes only in the control group, r = 0.52, p < 0.005 for AAP, r = -0.43, p < 0.02 for GGT, and r = -0.23, p < 0.05 for β-NAG. Our results suggest that after long-term administration of NSAIDs, toxic renal tubular involvement is frequent, that urinary excretion of three specific renal tubular enzymes could be a suitable tracer of the toxic effects of the drugs at the cellular level, and that prolonged cellular injury could lead toward progressive renal damage, with a rather “silent” clinical picture.