Incidence and predictors of vancomycin nephrotoxicity and mortality in patients with chronic liver disease: a two-center retrospective cohort study.

Abstract

Background: Patients with liver disease express multiple pathophysiological variations that alter the pharmacokinetics of numerous drugs. At this time, there is insufficient evidence about the proper dosing of vancomycin in patients with liver disease. This study aimed to assess the risk of acute kidney injury (AKI) during vancomycin therapy and identify predictors of AKI and all-cause mortality among patients with varying degrees of liver dysfunction.

Methods: A retrospective cohort study was conducted including patients with chronic liver disease who used vancomycin during hospitalization from January 2016 to January 2024 in two Saudi hospitals. Patients were grouped by the severity of the liver disease (mild liver disease [MLD] or moderate-to-severe liver disease [MSLD] based on the Child-Pugh score). The incidence of AKI, vancomycin mean trough level, and all-cause mortality were compared between the two groups. A multivariable logistic regression model was employed to identify predictors of AKI and mortality.

Results: A total of 110 patients treated with vancomycin were included in this study (28 had MLD and 82 had MSLD). A higher incidence of AKI in patients with MSLD than those with MLD was observed (28% vs. 14.3%, respectively; p = 0.1440), but the difference was statistically insignificant. The vancomycin mean trough levels (12.9 ± 5.2 μmol/L vs. 10.2 ± 4.7 μmol/L, p = 0.0143) and the percentage of patients with vancomycin trough level > 13.8 μmol/L (35.4% vs. 10.7%, p = 0.0131) were significantly higher in the MSLD group compared to the MLD group. Having a Creatinine Clearance (CrCl) between 15.1-29.9 ml/min (adjusted Odds ratio [aOR]: 45.5; 95% Confidence interval [CI] 4.99-414.8), and a vancomycin mean trough level > 13.8 μmol/L (aOR: 7.67; 95%CI 2.49-23.63) were associated with a higher risk of AKI development. Similarly, mortality was significantly higher in the MSLD group than in the MLD (23.2% vs. 3.6%, respectively; p = 0.0203). The risk of mortality was associated with having a body mass index (BMI) between 25-29.9 kg/m² (sOR 6.69; 95%CI 1.73-25.8), an albumin level < 25 g/L (aOR: 4.33; 95%CI 1.36-13.8), and a vancomycin mean trough level > 13.8 μmol/L (aOR: 6.13; 95%CI 1.82-20.6).

Conclusion: Patients who had MSLD had a higher trough vancomycin levels and mortality than patients who had MLD; and this risk increases as liver disease progresses. Thus, the existence of chronic liver disease should be considered when monitoring toxicity from vancomycin to minimize the risk of adverse outcomes and mortality. Larger studies are needed to closely quantify the risk of vancomycin toxicity among patients with chronic liver disease.