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Background & aims: Administration of glutamine in patients with renal dysfunction is considered to be potentially adverse. In a rat model of moderate kidney dysfunction dose-dependent effects of intravenous alanyl-glutamine infusion on possible biochemical and histological signs of toxicity were investigated. Methods: Rats with renal dysfunction resulting from 5/6 nephrectomy received a 9 days continuous intravenous infusion of either saline or 0.5 g/kg/day or 3.0 g/kg/day alanyl-glutamine (Dipeptiven ®) or 3.0 g/kg/day alanine. Dose-dependent effects on kidney and other organs were assessed by analyzing blood levels of creatinine, ammonia, urea, ALT, AST, ALP, pH, pO 2 , pCO 2 , glutamine, and histopathology. Results: Continuous intravenous infusion of 3.0 g/kg/day alanylglutamine increased plasma glutamine concentrations up to 60% without aggravating the underlying kidney injury. In contrast, the morphology of the kidneys was improved due to reduced glomerulosclerosis and tubular proteinaceous casts. An increase in plasma urea concentrations observed in the 3.0 g/kg/day alanylglutamine group only was not associated with worsening of the phenotype. Conclusions: Continuous intravenous infusion of alanyl-glutamine at 0.5 and 3.0 g/kg/day up to 9 consecutive days is safe in a rat Abbreviations: Ala-Gln, alanyl-glutamine; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPN, chronic progressive nephropathy; eGFR, estimated glomerular filtration rate; HCO 3 À , hydrogen carbonate; pO 2 , partial pressure of oxygen; pCO 2 , partial pressure of carbon dioxide; tCO 2 , total carbon dioxide; sO 2 , oxygen saturation.

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s u m m a r yBackground & aims: Administration of glutamine in patients with liver failure is thought to possibly increase blood ammonia levels, thereby contributing to hepatic encephalopathy. In a rat model of moderate liver dysfunction with elevated plasma glutamine concentrations dose-dependent effects of intravenous alanylglutamine infusion on possible biochemical and histological signs of toxicity were investigated. Methods: Rats with moderate liver dysfunction resulting from alpha-naphthylisothiocyanate (ANIT) induced cholestasis received a 9 days continuous intravenous infusion of 0.5 g/kg/day or 3.0 g/ kg/day alanyl-glutamine (Dipeptiven ® ). Dose-dependent effects on liver injury were assessed by analyzing blood levels of ammonia, urea, ALT, AST, and ALP, glutamine, and histopathology. Results: Continuous intravenous infusion of 3.0 g/kg/day alanylglutamine increased plasma glutamine concentrations up to 30% without increasing blood ammonia levels or inducing astrocyte swelling. Alanyl-glutamine did not aggravate underlying liver injury shown by absent increase in plasma levels of ALT, AST, ALP and no signs of histopathologic alterations. Conclusions: Continuous intravenous infusion of alanyl-glutamine at 0.5 and 3.0 g/kg/day up to 9 consecutive days is safe in a rat model of moderate liver dysfunction based on ANIT-induced cholestasis.