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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

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

A Commentary to this article was published on 06 November 2019

Abstract

Background

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

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

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References

  1. Hermsen ED, Hanson M, Sankaranarayanan J, et al. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf. 2010;9(1):9–14. https://doi.org/10.1517/14740330903413514.

    Article  CAS  PubMed  Google Scholar 

  2. Finch NA, Zasowski EJ, Murray KP, et al. A quasi-experiment to study the impact of vancomycin area under the concentration-time curve-guided dosing on vancomycin-associated nephrotoxicity. Antimicrob Agents Chemother. 2017. https://doi.org/10.1128/aac.01293-17.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Martin JH, Norris R, Barras M, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society Of Infectious Diseases Pharmacists. Clin Biochem Rev. 2010;31(1):21–4.

    PubMed  PubMed Central  Google Scholar 

  4. Matsumoto K, Takesue Y, Ohmagari N, et al. Practice guidelines for therapeutic drug monitoring of vancomycin: a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. J Infect Chemother. 2013;19(3):365–80. https://doi.org/10.1007/s10156-013-0599-4.

    Article  PubMed  Google Scholar 

  5. Ye ZK, Chen YL, Chen K, et al. Therapeutic drug monitoring of vancomycin: a guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. J Antimicrob Chemother. 2016;71(11):3020–5. https://doi.org/10.1093/jac/dkw254.

    Article  PubMed  Google Scholar 

  6. Zhou Y, Gao F, Chen C, et al. Development of a population pharmacokinetic model of vancomycin and its application in Chinese geriatric patients with pulmonary infections. Eur J Drug Metab Pharmacokinet. 2018. https://doi.org/10.1007/s13318-018-0534-2.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Elyasi S, Khalili H, Dashti-Khavidaki S, et al. Vancomycin-induced nephrotoxicity: mechanism, incidence, risk factors and special populations. A literature review. Eur J Clin Pharmacol. 2012;68(9):1243–55. https://doi.org/10.1007/s00228-012-1259-9.

    Article  CAS  PubMed  Google Scholar 

  8. Liang X, Fan Y, Yang M, et al. A prospective multicenter clinical observational study on vancomycin efficiency and safety with therapeutic drug monitoring. Clin Infect Dis. 2018;67(suppl_2):S249–55. https://doi.org/10.1093/cid/ciy680.

    Article  CAS  PubMed  Google Scholar 

  9. Chen YC, Feng JF, Li B, et al. Estimation of safe and effective dose of vancomycin in MRSA-infected patients using serum cystatin C concentrations. Int J Clin Pharmacol Ther. 2013;51(3):161–9. https://doi.org/10.5414/CP201776.

    Article  CAS  PubMed  Google Scholar 

  10. Deng C, Liu T, Zhou T, et al. Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis. Int J Clin Pharmacol Ther. 2013;51(5):407–15. https://doi.org/10.5414/CP201842.

    Article  CAS  PubMed  Google Scholar 

  11. Keshavarzi F. Renal function overestimation in underweight and/or non-ambulatory patients. Int J Clin Pharm. 2015;37(5):675–7. https://doi.org/10.1007/s11096-015-0157-5.

    Article  PubMed  Google Scholar 

  12. Hermida J, Tutor JC. Serum cystatin C for the prediction of glomerular filtration rate with regard to the dose adjustment of amikacin, gentamicin, tobramycin, and vancomycin. Ther Drug Monit. 2006;28(3):326–31. https://doi.org/10.1097/01.ftd.0000211805.89440.3d.

    Article  CAS  PubMed  Google Scholar 

  13. Okamoto G, Sakamoto T, Kimura M, et al. Serum cystatin C as a better marker of vancomycin clearance than serum creatinine in elderly patients. Clin Biochem. 2007;40(7):485–90. https://doi.org/10.1016/j.clinbiochem.2007.01.008.

    Article  CAS  PubMed  Google Scholar 

  14. Tanaka A, Aiba T, Otsuka T, et al. Population pharmacokinetic analysis of vancomycin using serum cystatin C as a marker of renal function. Antimicrob Agents Chemother. 2010;54(2):778–82. https://doi.org/10.1128/AAC.00661-09.

    Article  CAS  PubMed  Google Scholar 

  15. Barr EL, Maple-Brown LJ, Barzi F, et al. Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: the eGFR study. Clin Biochem. 2017;50(6):301–8. https://doi.org/10.1016/j.clinbiochem.2016.11.024.

    Article  CAS  PubMed  Google Scholar 

  16. Bjork J, Grubb A, Gudnason V, et al. Comparison of glomerular filtration rate estimating equations derived from creatinine and cystatin C: validation in the Age, Gene/Environment Susceptibility-Reykjavik elderly cohort. Nephrol Dial Transplant. 2018;33(8):1380–8. https://doi.org/10.1093/ndt/gfx272.

    Article  CAS  PubMed  Google Scholar 

  17. Bjork J, Back SE, Ebert N, et al. GFR estimation based on standardized creatinine and cystatin C: a European multicenter analysis in older adults. Clin Chem Lab Med. 2018;56(3):422–35. https://doi.org/10.1515/cclm-2017-0563.

    Article  CAS  PubMed  Google Scholar 

  18. Liu TT, Pang HM, Jing L, et al. A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of renal function. J Pharm Pharmacol. 2019. https://doi.org/10.1111/jphp.13071.

    Article  PubMed  Google Scholar 

  19. Hoek FJ, Kemperman FA, Krediet RT. A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. Nephrol Dial Transplant. 2003;18(10):2024–31. https://doi.org/10.1093/ndt/gfg349.

    Article  CAS  PubMed  Google Scholar 

  20. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. https://doi.org/10.1159/000180580.

    Article  CAS  PubMed  Google Scholar 

  21. Deng C, Liu T, Wu K, et al. Predictive performance of reported population pharmacokinetic models of vancomycin in Chinese adult patients. J Clin Pharm Ther. 2013;38(6):480–9. https://doi.org/10.1111/jcpt.12092.

    Article  CAS  PubMed  Google Scholar 

  22. Guo T, van Hest RM, Roggeveen LF, et al. External evaluation of population pharmacokinetic models of vancomycin in large cohorts of intensive care patients. Antimicrob Agents Chemother. 2019. https://doi.org/10.1128/AAC.02543-18.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hu C, Yin WJ, Li DY, et al. Evaluating tacrolimus pharmacokinetic models in adult renal transplant recipients with different CYP3A5 genotypes. Eur J Clin Pharmacol. 2018;74(11):1437–47. https://doi.org/10.1007/s00228-018-2521-6.

    Article  CAS  PubMed  Google Scholar 

  24. Zhao CY, Jiao Z, Mao JJ, et al. External evaluation of published population pharmacokinetic models of tacrolimus in adult renal transplant recipients. Br J Clin Pharmacol. 2016;81(5):891–907. https://doi.org/10.1111/bcp.12830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Medellin-Garibay SE, Ortiz-Martin B, Rueda-Naharro A, et al. Pharmacokinetics of vancomycin and dosing recommendations for trauma patients. J Antimicrob Chemother. 2016;71(2):471–9. https://doi.org/10.1093/jac/dkv372.

    Article  CAS  PubMed  Google Scholar 

  26. Adane ED, Herald M, Koura F. Pharmacokinetics of vancomycin in extremely obese patients with suspected or confirmed Staphylococcus aureus infections. Pharmacotherapy. 2015;35(2):127–39. https://doi.org/10.1002/phar.1531.

    Article  CAS  PubMed  Google Scholar 

  27. Roberts J, Taccone F, Udy A, et al. Vancomycin dosing in critically ill patients: robust methods for improved continuous-infusion regimens. Antimicrob Agents Chemother. 2011;55(6):2704–9.

    Article  CAS  Google Scholar 

  28. Sanchez JL, Dominguez AR, Lane JR, et al. Population pharmacokinetics of vancomycin in adult and geriatric patients: comparison of eleven approaches. Int J Clin Pharmacol Ther. 2010;48(8):525–33.

    Article  CAS  Google Scholar 

  29. Revilla N, Martin-Suarez A, Perez MP, et al. Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation. Br J Clin Pharmacol. 2010;70(2):201–12. https://doi.org/10.1111/j.1365-2125.2010.03679.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Thomson AH, Staatz CE, Tobin CM, et al. Development and evaluation of vancomycin dosage guidelines designed to achieve new target concentrations. J Antimicrob Chemother. 2009;63(5):1050–7. https://doi.org/10.1093/jac/dkp085.

    Article  CAS  PubMed  Google Scholar 

  31. Staatz CE, Byrne C, Thomson AH. Population pharmacokinetic modelling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery. Br J Clin Pharmacol. 2006;61(2):164–76. https://doi.org/10.1111/j.1365-2125.2005.02547.x.

    Article  CAS  PubMed  Google Scholar 

  32. Llopis-Salvia P, Jimenez-Torres NV. Population pharmacokinetic parameters of vancomycin in critically ill patients. J Clin Pharm Ther. 2006;31(5):447–54. https://doi.org/10.1111/j.1365-2710.2006.00762.x.

    Article  CAS  PubMed  Google Scholar 

  33. Buelga DS, de del Mar Fernandez M, Herrera EV, et al. Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies. Antimicrob Agents Chemother. 2005;49(12):4934–41. https://doi.org/10.1128/aac.49.12.4934-4941.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yasuhara M, Iga T, Zenda H, et al. Population pharmacokinetics of vancomycin in Japanese adult patients. Ther Drug Monit. 1998;20(2):139–48.

    Article  CAS  Google Scholar 

  35. Purwonugroho TA, Chulavatnatol S, Preechagoon Y, et al. Population pharmacokinetics of vancomycin in Thai patients. Sci World J. 2012;2012:762649. https://doi.org/10.1100/2012/762649.

    Article  CAS  Google Scholar 

  36. He XR, Liu ZH, Ji SM, et al. Population pharmacokinetics of vancomycin and prediction of pharmacodynamics in the Chinese people. Yao Xue Xue Bao. 2014;49(11):1528–35.

    PubMed  Google Scholar 

  37. Lin WW, Wu W, Jiao Z, et al. Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens. Eur J Clin Pharmacol. 2016;72(1):29–37. https://doi.org/10.1007/s00228-015-1952-6.

    Article  CAS  PubMed  Google Scholar 

  38. Wu CC, Shen LJ, Hsu LF, et al. Pharmacokinetics of vancomycin in adults receiving extracorporeal membrane oxygenation. J Formos Med Assoc. 2016;115(7):560–70. https://doi.org/10.1016/j.jfma.2015.05.017.

    Article  CAS  PubMed  Google Scholar 

  39. Ji XW, Ji SM, He XR, et al. Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients. Acta Pharmacol Sin. 2017. https://doi.org/10.1038/aps.2017.57.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sheiner LB, Rosenberg B, Melmon KL. Modelling of individual pharmacokinetics for computer-aided drug dosage. Comput Biomed Res. 1972;5(5):411–59.

    Article  CAS  Google Scholar 

  41. Sheiner LB, Rosenberg B, Marathe VV. Estimation of population characteristics of pharmacokinetic parameters from routine clinical data. J Pharmacokinet Biopharm. 1977;5(5):445–79.

    Article  CAS  Google Scholar 

  42. Shin JE, Lee SM, Eun HS, et al. Usefulness of serum cystatin C to determine the dose of vancomycin in neonate. Korean J Pediatr. 2015;58(11):421–6. https://doi.org/10.3345/kjp.2015.58.11.421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Frazee EN, Rule AD, Herrmann SM, et al. Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study. Crit Care. 2014;18(3):R110. https://doi.org/10.1186/cc13899.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tanaka A, Suemaru K, Otsuka T, et al. Hoek’s formula, a cystatin C-based prediction formula for determining the glomerular filtration rate, is the most effective method for original adjusting the dosage of vancomycin. Int J Clin Pharmacol Ther. 2007;45(11):592–7.

    Article  CAS  Google Scholar 

  45. Chi X, Li G, Wang Q, et al. CKD-EPI creatinine-cystatin C glomerular filtration rate estimation equation seems more suitable for Chinese patients with chronic kidney disease than other equations. BMC Nephrol. 2017;18(1):226.

    Article  Google Scholar 

  46. Suzuki A, Imanishi Y, Nakano S, et al. Usefulness of serum cystatin C to determine the dose of vancomycin in critically ill patients. J Pharm Pharmacol. 2010;62(7):901–7. https://doi.org/10.1211/jpp.62.07.0011.

    Article  CAS  PubMed  Google Scholar 

  47. Tanaka A, Suemaru K, Otsuka T, et al. Estimation of the initial dose setting of vancomycin therapy with use of cystatin C as a new marker of renal function. Ther Drug Monit. 2007;29(2):261–4. https://doi.org/10.1097/FTD.0b013e31803bcfd2.

    Article  CAS  PubMed  Google Scholar 

  48. Grubb A, Bjork J, Nyman U, et al. Cystatin C, a marker for successful aging and glomerular filtration rate, is not influenced by inflammation. Scand J Clin Lab Invest. 2011;71(2):145–9. https://doi.org/10.3109/00365513.2010.546879.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shigemura M, Konno S, Nasuhara Y, et al. Impact of asthmatic control status on serum cystatin C concentrations. Clin Chem Lab Med. 2012;50(8):1367–71.

    CAS  PubMed  Google Scholar 

  50. Zhai JL, Ge N, Zhen Y, et al. Corticosteroids significantly increase serum cystatin C concentration without affecting renal function in symptomatic heart failure. Clin Lab. 2016;62(1–2):203–7.

    CAS  PubMed  Google Scholar 

  51. Pianta TJ, Pickering JW, Succar L, et al. Dexamethasone modifies cystatin c-based diagnosis of acute kidney injury during cisplatin-based chemotherapy. Kidney Blood Press Res. 2017;42(1):62–75. https://doi.org/10.1159/000469715.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

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.

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Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China

    Ren Zhang, Ming Chen, Tao-tao Liu, Jie-Jiu Lu & Chun-le Lv

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  1. Ren Zhang
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Correspondence to Tao-tao Liu.

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Funding

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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Zhang, R., Chen, M., Liu, Tt. et al. 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. Eur J Drug Metab Pharmacokinet 45, 135–149 (2020). https://doi.org/10.1007/s13318-019-00578-4

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