Investigation of Aminoglycoside Nephrotoxicity in Cystic Fibrosis Patients

Abstract

Cystic flbrosis patients are a special risk group for nephrotoxic effects of aminoglycosides (AG). The traditional methods of assessing renal damage are very insensitive, and toxicity is not detected until serious functional damage is evident. The aims of the present study were to monitor early markers of nephrotoxicity in cystic fibrosis patients treated with gentamicin. Urinary excretion of β-N-acetylglucosaminase β-NAG, a lysosomal enzyme) and low molecular weight proteins as identified on sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) were prospectively studied in cystic fibrosis outpatients and inpatients. Urinary excretions of β-N AG and low molecular weight proteins were normal in cystic fibrosis patients not being treated with gentamicin. All patients being treated with intravenous gentamicin (average dose, 2.5 g over 9 days) showed markedly elevated urinary excretion of β-NAG. SDS-PAGE of serial urine samples from CF patients during intravenous AG therapy showed increasing excretion of low molecular weight proteins. Protein excretion profiles from control subjects showed no change over equivalent time periods. CF patients receiving nebulized AG did not show altered protein excretion. β-NAG excretion patterns were similar to changes detected in the SDS-PAGE system. No gross nephrotoxicity developed in these patients. Blood urea nitrogen, plasma creatinine, and plasma magnesium concentrations remained within normal limits. The pattern of protein excretion on SDS-PAGE was consistent with renal tubular rather than glomerular damage. The SDS-PAGE system provides an additional means of monitoring early subclinical nephrotoxicity of AG in CF patients.

Key Words:

• β-N-Acetylglucosaminidase
• cystic fibrosis
• gentamicin
• nephrotoxicity
• low molecular weight proteins