Hye Kyung Han1, Hyungmi An, Kwang-Hee Shin, Donghoon Shin, Sue Hyun Lee, Ju Han Kim, Sang-Heon Cho, Hye-Ryun Kang, In-Jin Jang, Kyung-Sang Yu, Kyoung Soo Lim. 1. *Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital; †Department of Statistics, Seoul National University; ‖College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu; ‡Seoul National University Biomedical Informatics (SNUBI), Division of Biomedical Informatics, Seoul National University College of Medicine; §Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University College of Medicine and Hospital; and ¶Drug Safety Management Center, Seoul National University Hospital, Korea.
Abstract
BACKGROUND: High doses of vancomycin increase the risk of nephrotoxicity, but the quantitative relationship between vancomycin exposure and nephrotoxicity is still controversial. This study evaluated the relationship between vancomycin trough concentration and nephrotoxicity, and risk factors for nephrotoxicity in patients undergoing therapeutic drug monitoring. METHODS: A total of 1269 cases from patients who underwent therapeutic drug monitoring were collected from 2006 to 2010. Receiver operating characteristic curve analysis was used to evaluate the relationship between trough concentration and the incidence of nephrotoxicity. Logistic regression using the generalized Least Absolute Shrinkage and Selection Operator (lasso) method was used to evaluate possible risk factors for nephrotoxicity. The data were divided into high/low-concentration groups by the cutoff value obtained from the receiver operating characteristic curve, and additional logistic regression using the generalized lasso method was performed for each group. RESULTS: The cutoff value of the vancomycin trough concentration was 12.1 mg/L. Patients with high concentrations (>12.1 mg/L) were more likely to develop nephrotoxicity (odds ratio = 16.0, 95% confidence interval, 8.2-31.1). The vancomycin trough concentration was the only significant risk factor for nephrotoxicity identified using the generalized lasso (P < 0.001). In contrast, no factor was associated with nephrotoxicity in the low-concentration group. CONCLUSIONS: Vancomycin trough concentrations over 12.1 mg/L were associated with an increased risk of nephrotoxicity. This is lower than the known threshold. Trough vancomycin concentration over the threshold was the only risk factor of nephrotoxicity among demographic factors, dosing regimen, and other clinical conditions in this study. It is suggested that vancomycin trough concentrations greater than 12.1 mg/L require close monitoring for nephrotoxicity.
BACKGROUND: High doses of vancomycin increase the risk of nephrotoxicity, but the quantitative relationship between vancomycin exposure and nephrotoxicity is still controversial. This study evaluated the relationship between vancomycin trough concentration and nephrotoxicity, and risk factors for nephrotoxicity in patients undergoing therapeutic drug monitoring. METHODS: A total of 1269 cases from patients who underwent therapeutic drug monitoring were collected from 2006 to 2010. Receiver operating characteristic curve analysis was used to evaluate the relationship between trough concentration and the incidence of nephrotoxicity. Logistic regression using the generalized Least Absolute Shrinkage and Selection Operator (lasso) method was used to evaluate possible risk factors for nephrotoxicity. The data were divided into high/low-concentration groups by the cutoff value obtained from the receiver operating characteristic curve, and additional logistic regression using the generalized lasso method was performed for each group. RESULTS: The cutoff value of the vancomycin trough concentration was 12.1 mg/L. Patients with high concentrations (>12.1 mg/L) were more likely to develop nephrotoxicity (odds ratio = 16.0, 95% confidence interval, 8.2-31.1). The vancomycin trough concentration was the only significant risk factor for nephrotoxicity identified using the generalized lasso (P < 0.001). In contrast, no factor was associated with nephrotoxicity in the low-concentration group. CONCLUSIONS:Vancomycin trough concentrations over 12.1 mg/L were associated with an increased risk of nephrotoxicity. This is lower than the known threshold. Trough vancomycin concentration over the threshold was the only risk factor of nephrotoxicity among demographic factors, dosing regimen, and other clinical conditions in this study. It is suggested that vancomycin trough concentrations greater than 12.1 mg/L require close monitoring for nephrotoxicity.
Authors: Reza Zonozi; Aozhou Wu; Jung-Im Shin; Alex Secora; Josef Coresh; Lesley A Inker; Alex R Chang; Morgan E Grams Journal: Mayo Clin Proc Date: 2019-01 Impact factor: 7.616
Authors: Jim C E Odekerken; Dorien M W Logister; Loubna Assabre; Jacobus J C Arts; Geert H I M Walenkamp; Tim J M Welting Journal: Springerplus Date: 2015-10-15
Authors: John David Clements; Juan Jose Perez Ruixo; John P Gibbs; Sameer Doshi; Carlos Perez Ruixo; Murad Melhem Journal: CPT Pharmacometrics Syst Pharmacol Date: 2018-10-15