Nephrotoxicity of tobramycin. Value of examining various protein and enzyme markers.

The value of various protein and enzyme markers for the assessment of early nephrotoxicity of tobramycin was studied in 18 patients with febrile infection. The renal clearance of creatinine and the excretion of the following protein and enzyme markers were measured on the first and the last day of the 5-8 day treatment period: albumin, N-acetyl-beta-D-glucosaminidase (NAG), beta 2-microglobulin, alpha-amylase, lysozyme and retinol-binding protein (RBP). Diurnal excretions of beta 2-microglobulin, lysozyme and RBP, all markers of tubular dysfunction, were already increased on the first treatment day, compared to similar control patients treated with non-aminoglycoside antibiotics and reference values of our laboratory. The excretion of NAG, an enzyme released from tubular cell lysosomes, was not increased initially, but on the last treatment day it was increased most consistently of all the markers studied. Glomerular filtration rate was halved in 5 of the patients. The results suggest that the initial increase in beta 2-microglobulin, lysozyme and RBP excretion is a result of an early tubular transfer block by tobramycin, whereas the late increase in NAG excretion probably reflects the progress of tubular cell damage during the course of aminoglycoside therapy.