Investigation on the association between Osteopontin and Apolipoprotein E gene polymorphisms and vancomycin-induced acute kidney injury: A pharmacokinetic/pharmacogenetic study in critically ill patients

Abstract

Vancomycin is a commonly administered antibiotic for various Gram-positive infections in critically ill patients. Vancomycin has a narrow therapeutic index and its main adverse drug reaction is acute kidney injury (AKI). In this regard, various pharmacokinetic parameters have been widely considered for therapeutic drug monitoring (TDM) purposes. Higher vancomycin trough concentration and area under the curve (AUC) values would be associated with higher rates of AKI. Therefore, dose adjustment based on targeted pharmacokinetic values would be essential to avoid toxicity and achieve optimal clinical response. However, there are numerous reports regarding the discrepancy between pharmacokinetic parameter values and AKI. In this regard, we examined the possible role of pharmacogenetics in vancomycin-induced AKI to distinguish patients who are genetically prone to AKI. In this cross-sectional study, polymorphisms of osteopontin (OPN) and Apolipoprotein E (APOE) along with pharmacokinetic parameters were assessed in 87 critically ill patients admitted to ICU wards and received vancomycin. The results indicated a significant difference in OPN and APOE genotype distribution between AKI and non-AKI patients (P = 0.001 and 0.02, respectively). Stepwise multivariate logistic regression analysis showed that patients with e2e3 genotype were 4.2-fold more prone to AKI (P = 0.029; OR = 4.2; 95 %CI = 1.2–15.7). Moreover, there was a significant correlation between pharmacokinetic parameters (calculated trough concentration, AUCτ, AUC_24h, and t_1/2) and vancomycin-induced AKI. Genotyping the patients for OPN and APOE polymorphisms before vancomycin initiation would be promising as a routine clinical practice to obtain an efficient clinical response and prevent vancomycin-induced AKI, especially in critically ill patients.