Effects of Gentamicin Therapy on Urinary Excretion of Retinol-Binding Protein, Lysozyme and Electrolytes

Abstract

The urinary excretions of the low molecular weight proteins, retinol binding protein (RBP) and lysozyme, were investigated in 28patients treated with gentamicin (an aminoglycoside antibiotic) at East Birmingham Hospital. A control group of 21 surgical patients, not receiving aminoglycoside antibiotics, was also studied. The aim of the study was to investigate these two proteins as urinary indicators of drug-induced proximal tubular damage, such as that caused by the aminoglycoside antibiotics. The urinary excretions and plasma levels of calcium and magnesium were also studied in these patients to investigate any changes in electrolyte homeostasis due to aminoglycoside therapy. Lysozyme was measured by an established turbidometric assay. An enzyme-linked immunosorbent assay for determination of RBP was specially developed for this study. Calcium and magnesium were determined by atomic absorption spectrophotometry. RBP and lysozyme both proved too sensitive and non-specific to use in clinical practice as urinary markers of drug-induced proximal tubular damage. It was not possible to identify those patients who later developed nephrotoxicity, as excretion of both proteins was raised in most patients treated with gentamicin, whether or not plasma creatinine was significantly raised. Urinary excretions of both these proteins were also raised, after surgery, in patients who did not receive aminoglycosides and showed no significant rise in Pcr. The highest excretions of RBP and lysozyme were shown by gentamicin-treated surgical patients, possibly due to a combination of surgery, infection and gentamicin therapy. Patients with cystic fibrosis who were treated with gentamicin had normal or only slightly raised excretions of both proteins despite longer courses of therapy. Hypomagnesaemia and hypocalcaemia, which were very mild, occurred in only a few patients and no evidence was found for an effect of gentamicin on electrolyte excretion. The absence of significant effects on electrolyte homeostasis may be attributable to the relatively short courses of gentamicin therapy, whereas previously published reports of hypomagnesaemic hypocalcaemia involved long-term, high-dose gentamicin therapy.