伏立康唑致急性肾损伤和电解质紊乱的危险因素及与稳态谷浓度相关性研究OA

Objective To investigate the risk factors of voriconazole-induced acute kidney injury(AKI)and electrolyte disturbance and its correlation with steady-state trough concentration.Methods Clinical data of patients who received voriconazole treatment(≥3 d)and underwent steady-state trough concentration monitoring in a tertiary hospital from January 2021 to December 2023 were retrospectively collected.Blood drug concentrations were monitored according to the stratified voriconazole target range(0.5-5 mg/L).The distribution of steady-state trough concentrations among patients with different ages,daily doses and AKI status was compared to verify the dose-concentration linear relationship.According to the occurrence of adverse drug reactions(ADR),patients were divided into the AKI group and the non-AKI group,as well as the electrolyte disturbance group and the non-electrolyte disturbance group.Univariate and multivariate Logistic regression analyses were used to identify the risk factors of voriconazole-induced AKI and electrolyte disturbance.Receiver operating characteristic(ROC)curve was applied to evaluate the predictive efficacy of voriconazole steady-state trough concentration for AKI.Results A total of 249 patients were included,the incidence of AKI was 17.27%(43 cases).Univariate and multivariate Logistic regression analyses showed that voriconazole steady-state trough concentration≥4.78 mg/L and intravenous administration were independent risk factors for AKI(P<0.05).Stratified analysis results indicated that the steady-state trough concentration of patients was 0.44-15.27 mg/L,with significant individual differences,and no linear correlation with daily dose.The average steady-state trough concentration of voriconazole in pediatric patients(<18 years old)and elderly patients(>65 years old)was higher than that in adult patients(18-65 years old).The incidence of AKI showed an upward trend with the increase of steady-state trough concentration,mainly concentrated in the range of≥3.00 mg/L.The ROC curve analysis results revealed that the area under the curve of steady-state trough concentration for predicting AKI was 0.66,and the critical value of Youden index was 4.78 mg/L.The incidence of electrolyte disturbance among patients was 41.37%(103 cases),mainly including hypokalemia(66.02%)and hyponatremia(51.46%).Univariate analysis results showed that there were no significant differences in gender,age,daily dose,administration route,combined medication,steady-state trough concentration and primary disease between the electrolyte disturbance group and the non-electrolyte disturbance group(P>0.05).Stratified analysis results showed that the proportion of hypokalemia was higher than that of hyponatremia when the voriconazole steady-state trough concentration was 0.5-<3 mg/L and≥5 mg/L.Conclusion Voriconazole steady-state trough concentration≥4.78 mg/L and intravenous administration are independent risk factors for AKI.However,there are no specific high-risk factors for voriconazole-induced electrolyte disturbance.It is recommended that routine electrolyte monitoring should be performed for all patients receiving voriconazole.Meanwhile,enhanced monitoring of voriconazole trough concentration should be implemented in pediatric,elderly and intravenous patients,and oral administration should be preferred to ensure the safety of clinical medication.