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Trough Concentration Over 12.1 mg/L is a Major Risk Factor of Vancomycin-Related Nephrotoxicity in Patients With Therapeutic Drug Monitoring

Han, Hye Kyung MS*; An, Hyungmi BS*,†; Shin, Kwang-Hee PhD*,‖; Shin, Donghoon MD*; Lee, Sue Hyun MS; Kim, Ju Han MD, PhD; Cho, Sang-Heon MD, PhD§,¶; Kang, Hye-Ryun MD, PhD§,¶; Jang, In-Jin MD, PhD*,¶; Yu, Kyung-Sang MD, PhD*,¶; Lim, Kyoung Soo MD, PhD*,¶

doi: 10.1097/FTD.0000000000000061
Original Article

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.

*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.

Correspondence: Kyoung Soo Lim, MD, PhD, Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea (e-mail: kslim96@snu.ac.kr).

Supported in part by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012-0000994), the National Project for Personalized Genomic Medicine, Ministry for Health & Welfare, Republic of Korea (A111218-PG01), and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2011–0030815).

The authors declare no conflict of interest.

Received October 08, 2013

Accepted January 30, 2014

© 2014 by Lippincott Williams & Wilkins