Comparison of the Predictive Performance Between Cystatin C and Serum Creatinine by Vancomycin via a Population Pharmacokinetic Models: A Prospective Study in a Chinese Population

  • Ren Zhang
  • Ming Chen
  • Tao-tao LiuEmail author
  • Jie-Jiu Lu
  • Chun-le Lv
Original Research Article



Most of the current published population pharmacokinetic (PopPK) models are based on serum creatinine, but we often encounter an underestimation of its concentration in our clinical work. Therefore, we established a cystatin C-based model of vancomycin.


The purpose of this study was to externally verify the PopPK model of vancomycin based on the glomerular filtration rate (GFR) estimated by serum cystatin C in our previous study and to compare the prediction performance of cystatin C (Cys C) and serum creatinine (SCR)-based models.


The external data set consists of adults receiving vancomycin treatment at The First Affiliated Hospital of Guangxi Medical University. We summarized and restored published models based on serum creatinine values from the literature and used our external data set for initial screening. Visual and external verifications were used to further select candidate models for comparison. The mean prediction error (ME), mean absolute error (MAE) and root mean squared error (RMSE) were the primary outcomes for the overall comparison. Group comparisons of patients with different glomerular filtration rates (GFRs), ages and body mass index (BMI) levels were obtained by the Bayesian method.


A total of 156 patients with 233 samples were collected as an external data set. Sixteen published models were summarized and restored. After screening, four candidate models suitable for the external data set were finally obtained for comparison. The cystatin C-based model has a smaller ME value in the overall comparison. In the group comparison, serum creatinine-based models were underestimated in the prediction for patient groups with age ≥ 60 years, abnormal BMI values and GFR < 90 ml/min/1.73 m2, for which the cystatin C-based model could solve this problem.


After comparison, we suggest that cystatin C is a superior renal function marker to serum creatinine for vancomycin PopPK models.



We thank Dr. Zheng Jiao (Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China) for providing technical guidance on the population pharmacokinetics analysis.

Compliance with Ethical Standards


This work was supported by The National Natural Science Foundation of China under grant no. 81460569.

Conflict of Interest

Zhang Ren, Chen Ming, Lu Jiejiu, Lv Chunle and Liu Taotao have no conflicts of interest.

Ethics Approval

All procedures in this study were conducted in accordance with the 1964 Helsinki Declaration (and its amendments) and the guidelines of the ethics committee or institutional review board that approved the study.

Informed Consent

Written informed consent was obtained from all patients.


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PharmacyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina

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