Effect of serum concentration and concomitant drugs on vancomycin-induced acute kidney injury in haematologic patients: a single-centre retrospective study

  • Naoto OkadaEmail author
  • Masayuki Chuma
  • Momoyo Azuma
  • Shingen Nakamura
  • Hirokazu Miki
  • Hirofumi Hamano
  • Mitsuhiro Goda
  • Kenshi Takechi
  • Yoshito Zamami
  • Masahiro Abe
  • Keisuke Ishizawa
Pharmacokinetics and Disposition



Appropriate use of vancomycin (VCM) is important in preventing acute kidney injury (AKI). Because of the high frequency of VCM use for febrile neutropenia and concomitant use of other nephrotoxic drugs, haematologic patients have a different nephrotoxic background compared with patients with other diseases. Therefore, it is unclear whether the risk factors of VCM-induced AKI identified in other patient groups are also applicable to haematologic patients. Herein, we performed a single-centre retrospective analysis to identify the factors associated with VCM-induced AKI in haematologic patients.


We retrospectively analysed 150 haematologic patients to whom VCM was administered between April 2010 and March 2018 at Tokushima University Hospital. VCM-induced AKI was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression analyses were performed to identify risk factors for VCM-induced AKI.


Seventeen patients had VCM-induced AKI. Multivariate analysis revealed that the risk factors of VCM-induced AKI were an initial VCM trough concentration of > 15 mg/L and concomitant use of tazobactam/piperacillin (TAZ/PIPC) and liposomal amphotericin B (L-AMB). Patients with an initial VCM trough concentration of < 10 mg/L showed significantly lower efficacy in febrile neutropenia. Interestingly, concomitant L-AMB use increased the incidence of VCM-induced AKI in a VCM concentration–dependent manner, whereas concomitant TAZ/PIPC increased the incidence in a VCM concentration–independent manner.


The optimal initial VCM trough concentration was 10–15 mg/L in haematologic patients, considering safety and effectiveness. There were differences in the effect of VCM-induced AKI between nephrotoxic drugs.


Vancomycin Acute kidney injury Therapeutic drug monitoring Tazobactam/piperacillin Liposomal amphotericin B 


Authors’ contribution

NO reviewed the electronic records, performed the statistical analyses, and drafted the manuscript. MC assisted with the study design and drafted the manuscript. MA, SN, and HM reviewed the electronic records. HH, MG, KT, and YZ assisted with the study design. M. Abe and KI contributed to drafting the manuscript. All authors approved the final manuscript.

Funding information

This study was supported by a grant from the Japanese Society of Nephrology and Pharmacotherapy and JSPS KAKENHI Grant Number 19K16414.

Compliance with ethical standards

The survey content and methods to protect personal information were approved by the Tokushima University Hospital Ethics Committee and were in accordance with the stipulations on the handling of patient personal information (Ethics Committee Registration Number: 3245).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2019_2756_MOESM1_ESM.docx (127 kb)
ESM 1 (DOCX 127 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Naoto Okada
    • 1
    Email author
  • Masayuki Chuma
    • 2
  • Momoyo Azuma
    • 3
  • Shingen Nakamura
    • 4
  • Hirokazu Miki
    • 5
  • Hirofumi Hamano
    • 1
  • Mitsuhiro Goda
    • 1
  • Kenshi Takechi
    • 2
  • Yoshito Zamami
    • 1
    • 6
  • Masahiro Abe
    • 4
  • Keisuke Ishizawa
    • 1
    • 6
  1. 1.Department of PharmacyTokushima University HospitalTokushimaJapan
  2. 2.Clinical Trial Center for Developmental TherapeuticsTokushima University HospitalTokushimaJapan
  3. 3.Department of Infection Control and PreventionTokushima University HospitalTokushimaJapan
  4. 4.Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan
  5. 5.Division of Transfusion Medicine and Cell TherapyTokushima University HospitalTokushimaJapan
  6. 6.Department of Clinical Pharmacology and TherapeuticsTokushima University Graduate School of Biomedical SciencesTokushimaJapan

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