Relationship Between Vancomycin Trough Concentrations And Incidence Of Nephrotoxicity And Early Biological Markers In ICU Patients

Objective:To explore the relationship between vancomycin trough concentrations and incidence of nephrotoxicity in ICU patients, and to observe early biological markers of vancomycin-induced nephrotoxicity.Methods:1. Relationship between vancomycin trough concentrations and incidence of nephrotoxicity in ICU patients.This was a prospective randomized controlled trial. Hospitalized patients who received a course of vancomycin therapy between November2012and December2013in MICU of Lanzhou University Second Hospital were prospectively studied. Patients were randomly divided into low trough concentration group (5-10mg/L) and high trough concentration group (10-20mg/L) in a ratio of1:1. To determine if there is a difference in the effective rate and incidence of nephrotoxicity associated with the different vancomycin trough concentrations, in addition applying of multivariate logistic regression analysis of risk factors for development of nephrotoxicity.2. The significance of Kidney Injury Molecule-1and Cystatin C in early diagnosis of vancomycin-induced nephrotoxicity.This was a prospective trial. Hospitalized patients who received a course of vancomycin therapy for infection between November2012and December2013were prospectively studied. According to the nephrotoxicity criteria the patients were divided into nephrotoxicity group and non-nephrotoxicity group. Before and6h,12h,24h,48h after vancomycin therapy, the urine and serum sample were collected, serum creatinine, serum Cystatin C and urine KIM-1value were test. The area under the curve (AUC) of each biomarker in early diagnosis was calculated by receiver operating characteristic curve (ROC).Results:1. Relationship between vancomycin trough concentrations and incidence of nephrotoxicity in ICU patients.Of the83patients in the study,36in the group of low trough concentration (5-10mg/L) and 47in the group of high trough concentration (10-20mg/L). There were significant differences between two groups in clinical response (77.8%vs95.7%) and the average length of treatment (12.1±4.8vs10.0±3.4) days, P<0.05. No significant difference was observed between two groups in toxicity (5.5%vs8.5%, P=0.394). Independent predictors of vancomycin-induced nephrotoxicity in multivariate logistic regression analysis included age (OR=1.17;95%CI,1.01-1.36), APACHEII score (OR=1.48;95%CI,1.02-2.14), duration of vancomycin therapy≥14days (OR=1.15;95%CI,1.02-1.31), and concomitant other nephrotoxic agents (OR=1.38;95%CI,1.03-1.85).2. The significance of Kidney Injury Molecule-1and Cystatin C in early diagnosis of vancomycin-induced nephrotoxicity.13of80cases developed vancomycin-induced nephrotoxicity. Compared with non-nephrotoxicity group, serum creatinine, serum Cystatin C and utine KIM-1value were significantly higher in nephrotoxicity group at48h,12h, on after vancomycin inempy iespecuvery. There were statistically significances between the two groups (P<0.005). Through the ROC curve the AUC of serum Cystatin C and urine KIM-1were0.868vs0.922, the95%confidence interval were (0.776-0.961) vs (0.793-1.000).Conclusions:1. Relationship between vancomycin trough concentrations and incidence of nephrotoxicity in ICU patients.The higher vancomycin trough concentration had better clinical response compared with the lower trough concentration. Moreover incidence of nephrotoxicity was not apparent increase concomitantly. Age, APACHEII score, duration of vancomycin therapy≥14days, and concomitant other nephrotoxic agents were probably risk factors for vancomycin-induced nephrotoxicity.2. The significance of Kidney Injury Molecule-1and Cystatin C in early diagnosis of vancomycin-induced nephrotoxicity.Serum Cystatin C and urine KIM-1were helpful biomarkers for early diagnosis in patients of vancomycin-induced nephrotoxicity and the accuracy of urine KIM-1was better.