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Cystatin C and/or creatinine-based estimated glomerular filtration rate for prediction of vancomycin clearance in long-stay critically ill patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS): a population pharmacokinetics analysis

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Abstract

Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill patients are associated with unreliable creatinine (Cr)-based estimated glomerular filtration rate (eGFR) and alteration in vancomycin clearance (CL) due to ongoing muscle wasting and renal dysfunction (RD). Currently, cystatin C (Cys) is of great interest for eGFR due to its muscle independence. Patients receiving intravenous vancomycin with trough concentration monitoring after intensive care unit stay ≥ 14 days were retrospectively enrolled. Those with C-reactive protein > 30.0 mg/L, lymphocytes count < 0.80 × 109, albumin < 30 mg/L and weight loss > 10% were diagnosed with PICS. Impact of PICS on vancomycin trough achievement was analyzed. Plasma Cys and Cr levels with their eGFRs in RD were compared in patients with and without PICS. Furthermore, the performance of eGFRs in predicting vancomycin CL was quantificationally evaluated by population pharmacokinetics (PPK) analysis using the Phoenix NLME software. Of 69 enrolled patients, 32 (46.4%) were PICS. PICS was predictive of Cr-guided vancomycin supratherapeutic trough concentrations (OR = 5.26, P = 0.013). Significant elevation of Cys, not of Cr, was observed in patients with PICS suffering from RD (P = 0.022), causing substantial differences among eGFRs. Fifty-two and 17 patients were enrolled for the modeling group and validation group, respectively. A one-compartment PPK model with first-order elimination adequately described the data of 126 Ctrough. Prediction of vancomycin CL with Cys and Cr-based eGFR (CKD-EPIcys-cr) significantly reduced the interindividual variability of CL (from 75.6 to 28.5%). External validation with 34 Ctrough showed the robustness and accuracy of this model. This study showed the negative impact of PICS on Cr-guided vancomycin trough achievement. PPK model with CKD-EPIcys-cr can be used to optimize vancomycin dosage in patients with PICS.

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Acknowledgements

The authors thank the staff of the Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, for their collaboration and the use of their facilities.

Funding

Talent development project for three-year action plan of Shanghai public health system construction (No. GWV-10.2-XD03).

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  1. Jingjing Huang and Xiaoli Wang have contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jingjing Huang, Chenxia Hao, Wanhua Yang & Weixia Zhang

  2. Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin Er Road, Shanghai, 20025, China

    Xiaoli Wang, Jialin Liu & Hongping Qu

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  1. Jingjing Huang
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Contributions

HQ and JL were in charge of the entire project and reviewed the manuscript. JH designed the study and wrote the manuscript. XW performed the study and wrote the manuscript. WY, CH and WZ analyzed the data and interpreted the results.

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Correspondence to Jialin Liu or Hongping Qu.

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The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

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The study protocol was approved by Ruijin Hospital Research Ethics Committee (No.2018-106).

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This is a retrospective study. Vancomycin concentrations and renal biomarkers were routinely monitored in our hospital. And the use of the data has been approved by Ruijin Hospital Research Ethics Committee. So, informed consent was not applied to this study.

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Huang, J., Wang, X., Hao, C. et al. Cystatin C and/or creatinine-based estimated glomerular filtration rate for prediction of vancomycin clearance in long-stay critically ill patients with persistent inflammation, immunosuppression and catabolism syndrome (PICS): a population pharmacokinetics analysis. Intern Emerg Med 16, 1883–1893 (2021). https://doi.org/10.1007/s11739-021-02699-8

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