Aminoglycoside nephrotoxicity in cirrhosis. Value of urinary β2-microglobulin to discriminate functional renal failure from acute tubular damage

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Abstract

Thirty-five cirrhotics with suspected severe gram-negative infections, treated with aminoglycosides, were investigated to determine the incidence of aminoglycoside nephrotoxicity. The urinary concentration of β2-microglobulin (normal: 16-760 μg/ L), which was found to be normal in control patients with cirrhosis, either with or without functional renal failure, but very high in noncirrhotic patients with acute tubular necrosis (range: 3286-100,540 μg/L), was used as a marker of tubular damage. Twelve cases (group I) developed acute tubular damage during therapy (β2-microglobulin increased from normal to >3000 μg/L); none received aminoglycoside overdosage. In 1 patient tubular damage was due to hypovolemic shock; in the remaining 11 cases (31.4% of the whole series) no cause other than aminoglycoside treatment was found. All but one of these patients developed a decrease in renal function, which was severe in most cases. There was a closed chronological relationship between the increase of urinary β2-microglobulin and the appearance of renal function deterioration, suggesting aminoglycoside toxicity as the cause. Nine patients (group II) developed a functional renal impairment during therapy (decrease in renal function with no increase of β2-microglobulin). In 14 patients (group III) neither tubular damage nor a decrease in renal function occurred. On the day of highest serum creatinine, patients of groups I and II could not be differentiated on the basis of urine volume, urine sodium concentration, and urine-plasma osmolality ratio. Cases with and without nephrotoxicity differed with respect to pretherapy liver and renal function, both being worse in the first group. The incidence of nephrotoxicity was 52.9% in patients who had abnormal serum creatinine (>1.2 mg/100 ml) before therapy and only 11.1% in those with normal serum creatinine. Patients with nephrotoxicity also showed higher trough serum levels of aminoglycosides before the appearance of tubular damage. Our results indicate that aminoglycoside nephrotoxicity is frequent in advanced cirrhosis and that the measurement of markers of tubular damage is the only way to differentiate this condition from functional renal failure. © 1982.

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Cabrera, J., Arroyo, V., Ballesta, A. M., Rimola, A., Gual, J., Elena, M., & Rodes, J. (1982). Aminoglycoside nephrotoxicity in cirrhosis. Value of urinary β2-microglobulin to discriminate functional renal failure from acute tubular damage. Gastroenterology, 82(1), 97–105. https://doi.org/10.1016/0016-5085(82)90129-9

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