A focus of tissue necrosis increases renal susceptibility to gentamicin administration

Abstract

The purpose of this study was to determine whether a retained focus of necrotic tissue predisposes to aminoglycoside-induced acute renal failure (ARF). Rats were subjected to either (1) 25% liver ligation, creating a focus of ischemic tissue which was left in place; (2) 25% liver resection; or (3) sham liver ligation. Gentamicin, 80 mg/kg bid, was administered for two days after surgery to all three groups. A fourth group was subjected to 25% liver ligation but no gentamicin therapy. Only rats subjected to partial liver ligation plus gentamicin treatment developed ARF, manifested by azotemia (BUN 80 ± 2; creatinine 1.63 ± 0.21; mg/dl) and tubular necrosis. This occurred in the absence of any discernible reduction in arterial blood pressure, renal blood flow, excessive weight loss, or ascites formation. The partial liver ligation-gentamicin group had 70% higher renal gentamicin concentrations than the liver resection-gentamicin controls (P = 0.01). To assess whether factors released from necrotic liver might account for these findings, additional rats were infused with: (1) 1 ml of a soluble liver extract alone; (2) 1 ml of liver extract plus gentamicin; or (3) 1 ml of saline plus gentamicin. Only the liver extract/gentamicin group developed ARF (BUN 88 ± 13; creatinine 1.46 ± 0.25). This occurred in association with a 110% increase in renal gentamicin uptake (P < 0.03). In separate experiments, 5 ml liver extract infusions caused ARF (BUN 118 ± 7; creatinine 2.1 ± 0.18) without gentamicin treatment. In conclusion, a focus of liver necrosis can predispose to experimental gentamicin nephrotoxicity. This effect appears to be mediated by increased renal gentamicin uptake and possibly by release of nephrotoxic factors from necrotic tissue.