Acute kidney injury development is associated with mortality in Japanese patients with cirrhosis: impact of amino acid imbalance

Abstract

Background: Acute kidney injury (AKI) is a serious complication of cirrhosis. This study analyzed the prognostic effect of AKI in patients with cirrhosis and its risk factors, particularly in relation to amino acid imbalance.

Methods: This retrospective study reviewed 808 inpatients with cirrhosis at two institutes in Gifu, Japan. AKI was diagnosed according to the recommendations of the International Club of Ascites. Amino acid imbalance was assessed by measuring serum branched-chain amino acid (BCAA) levels, tyrosine levels, and the BCAA-to-tyrosine ratio (BTR). Factors associated with mortality and AKI development were assessed using the Cox proportional hazards regression model with AKI as a time-dependent covariate and the Fine-Gray competing risk regression model, respectively.

Results: Of the 567 eligible patients without AKI at baseline, 27% developed AKI and 25% died during a median follow-up period of 4.7 years. Using a time-dependent covariate, AKI development (hazard ratio [HR], 6.25; 95% confidence interval [CI], 3.98-9.80; p < 0.001) was associated with mortality in patients with cirrhosis independent of potential covariates. In addition, alcohol-associated/-related liver disease, metabolic dysfunction-associated steatohepatitis, Child-Pugh score, and BTR (subdistribution HR 0.78; 95% CI 0.63-0.96; p = 0.022) were independently associated with AKI development in patients with cirrhosis. Similar results were obtained in the multivariate model that included BCAA and tyrosine levels instead of BTR.

Conclusions: AKI is common and associated with mortality in Japanese patients with cirrhosis. An amino acid imbalance is strongly associated with the development of AKI in patients with cirrhosis.

Keywords: Acute kidney injury; Amino acid imbalance; Branched-chain amino acids; Hepatorenal syndrome; Survival.

Fig. 1

Overall survival of patients with cirrhosis by stage of acute kidney injury

Fig. 2

Cumulative incidence of AKI in patients with cirrhosis according to a etiology of cirrhosis and b Child–Pugh class. AKI acute kidney injury, ALD alcohol-associated/related liver disease, MASH metabolic dysfunction-associated steatohepatitis

Fig. 3

Cumulative incidence of AKI in patients with cirrhosis according to a BTR ≤ 4.4 and > 4.4, b BCAA < 344 μmol/L and ≥ 344 μmol/L, and c tyrosine > 98 μmol/L and ≤ 98 μmol/L. AKI acute kidney injury, BCAA branched-chain amino acid, BTR branched-chain amino acid-to-tyrosine ratio