Protective effects of reduced glutathione on renal toxicity induced by vancomycin in critically ill patients

Abstract

To observe the changes of renal function in critically ill patients after using vancomycin and analyze the renal protective effect of reduced glutathione (GSH) on vancomycin nephrotoxicity. The clinical data of patients with severe infection who were administered with vancomycin or plus infusion of GSH admitted to intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019 were collected during the study period, and the patients were divided into only vancomycin group and vancomycin combined with GSH group. The gender, age, body weight, underlying diseases, clinical diagnosis, severity score, renal function before and after taking the medicine, average daily dose and treatment duration of vancomycin and GSH, length of ICU stay and clinical outcomes were recorded and analyzed. A total of 217 patients were enrolled, with 127 patients in the only vancomycin group, and 90 in the combination with GSH group. There was no statistically significant difference between the two groups in terms of gender, body weight, duration of vancomycin treatment, history of chronic kidney disease, and ICU mortality. The main causes of 217 patients admitted to the ICU were lung infection, sepsis/septic shock, and severe acute pancreatitis (SAP) and so on. The majority of patients in only vancomycin group had lung infections (63.0%), while the main etiology in combination with GSH group was SAP (46.7%). Compared with the only vancomycin group, the acute physiology and chronic health evaluation II (APACHE II) score in the combination with GSH group significantly decreased [15.0 (10.5, 21.0) vs. 27.0 (20.0, 31.0), P < 0.01], but the quick sequential organ failure assessment (qSOFA) score was significantly higher [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], the basic renal function was poorer [serum creatinine (SCr, μmol/L): 102.0 (64.7, 178.0) vs. 56.0 (42.0, 71.0), blood urea nitrogen (BUN, mmol/L): 11.5 (6.7, 18.4) vs. 4.70 (3.5, 8.1), both P < 0.05], and the average daily dose of vancomycin was lower (mg×kg-1×d-1: 22.22±10.09 vs. 25.51±9.56, P < 0.05). The renal function of patients was getting worse significantly after vancomycin usage as compared with before [SCr (μmol/L): 68.0 (50.3, 103.4) vs. 56.0 (42.0, 71.0), BUN (mmol/L): 5.4 (3.6, 9.6) vs. 4.7 (3.5, 8.1), both P < 0.05]. However, the renal function indexes of the combination with GSH group were better than those before treatment [SCr (μmol/L): 81.0 (61.0, 129.0) vs. 102.0 (64.7, 178.0), P < 0.05; BUN (mmol/L): 8.4 (6.2, 17.8) vs. 11.5 (6.7, 18.4), P > 0.05], and the length of ICU stay was significantly shorter than that in the only vancomycin group [days: 29.0 (14.0, 54.2) vs. 37.0 (25.0, 55.0), P < 0.05]. The incidence of drug-induced renal injury caused by vancomycin is high. The GSH can significantly reduce their renal toxicity and shorten the length of hospital stay.