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Effect of discrepancy in estimated renal function on vancomycin area under the blood concentration–time curve: a retrospective cohort study comparing serum creatinine and serum cystatin C

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Abstract

Background

Accurate estimation of renal function is essential for determining vancomycin (VCM) dosing. Serum creatinine (sCr)-based formulas are used to estimate renal function; however, they may overestimate the glomerular filtration rate (GFR) in patients with reduced muscle mass. Serum cystatin C (cys-C) may provide more accurate estimates of renal function in such populations.

Aim

We aimed to investigate the effect of estimated GFR (eGFR) discordance on area under the blood concentration–time curve (AUC) of VCM.

Method

Data from 118 patients with simultaneous sCr and cys-C data available at start of VCM therapy were analyzed. Patients were classified into eGFR discordance and concordance groups. eGFR discordance was defined as a case where the sCr-based eGFR was 30% or higher than the cys-C-based eGFR. The primary outcome was the association between eGFR discordance and upward deviation of the VCM AUC.

Results

Seventy-two patients with eGFR discordance had significantly higher measurement of VCM AUC than predicted (p < 0.001). Multivariate logistic regression analysis identified age, hospital stay of ≥ 12 days, and eGFR discordance as significant predictors of AUC upward deviation. Factors associated with discordance in the eGFR included these risk factors and intensive care unit (ICU) stay.

Conclusion

This study highlights the importance of measuring cys-C levels at initiation of VCM therapy identifying patients at risk of renal function overestimation and subsequent VCM overdosing. Older with extended hospitalization or ICU stay may benefit from measuring cys-C levels of optimize VCM therapy and reduce drug-induced toxicity risk.

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References

  1. Tsutsuura M, Moriyama H, Kojima N, et al. The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing. BMC Infect Dis. 2021;21:153. https://doi.org/10.1186/s12879-021-05858-6.

    Article CAS PubMed PubMed Central Google Scholar

  2. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health System Pharmacists. Clin Infect Dis. 2020;71:1361–4. https://doi.org/10.1093/cid/ciaa303.

    Article CAS PubMed Google Scholar

  3. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in Renal Disease Study Group. Ann Intern Med. 1999;130:461–70. https://doi.org/10.7326/0003-4819-130-6-199903160-00002.

    Article CAS PubMed Google Scholar

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

    Article CAS PubMed Google Scholar

  5. Oda K, Katanoda T, Hashiguchi Y, et al. Development and evaluation of a vancomycin dosing nomogram to achieve the target area under the concentration-time curve. A retrospective study. J Infect Chemother. 2020;26:444–50. https://doi.org/10.1016/j.jiac.2019.11.009.

    Article CAS PubMed Google Scholar

  6. Takigawa M, Tanaka H, Obara T, et al. Utility of the Berlin Initiative Study-1 equation for the prediction of serum vancomycin concentration in elderly patients aged 75 years and older. Pharmazie. 2022;77:76–80. https://doi.org/10.1691/ph.2022.1972.

    Article CAS PubMed Google Scholar

  7. Inker LA, Eneanya ND, Coresh J, et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385:1737–49. https://doi.org/10.1056/NEJMoa2102953.

    Article CAS PubMed PubMed Central Google Scholar

  8. Shafi T, Zhu X, Lirette ST, et al. Quantifying individual-level inaccuracy in glomerular filtration rate estimation: a cross-sectional study. Ann Intern Med. 2022;175:1073–82. https://doi.org/10.7326/M22-0610.

    Article PubMed Google Scholar

  9. Ishigo T, Ibe Y, Fujii S, et al. Effect of renal clearance on vancomycin area under the concentration-time curve deviations in critically ill patients. J Infect Chemother. 2023;29:769–77. https://doi.org/10.1016/j.jiac.2023.04.018.

    Article CAS PubMed Google Scholar

  10. Haines RW, Fowler AJ, Liang K, et al. Comparison of cystatin C and creatinine in the assessment of measured kidney function during critical illness. Clin J Am Soc Nephrol. 2023;18:997–1005. https://doi.org/10.2215/CJN.0000000000000203.

    Article PubMed PubMed Central Google Scholar

  11. Teaford HR, Stevens RW, Rule AD, et al. Prediction of vancomycin levels using cystatin C in overweight and obese patients: a retrospective cohort study of hospitalized patients. Antimicrob Agents Chemother. 2020;65:e01487-e1520. https://doi.org/10.1128/AAC.01487-20.

    Article PubMed PubMed Central Google Scholar

  12. Frazee E, Rule AD, Lieske JC, et al. Cystatin C-guided vancomycin dosing in critically ill patients: a quality improvement project. Am J Kidney Dis. 2017;69:658–66. https://doi.org/10.1053/j.ajkd.2016.11.016.

    Article CAS PubMed Google Scholar

  13. Barreto EF, Rule AD, Murad MH, et al. Prediction of the renal elimination of drugs with cystatin C vs creatinine: a systematic review. Mayo Clin Proc. 2019;94:500–14. https://doi.org/10.1016/j.mayocp.2018.08.002.

    Article CAS PubMed Google Scholar

  14. Hanna PE, Wang Q, Strohbehn IA, et al. Medication-related adverse events and discordancies in cystatin C-based vs serum creatinine-based estimated glomerular filtration rate in patients with cancer. JAMA Netw Open. 2023;6:e2321715. https://doi.org/10.1001/jamanetworkopen.2023.21715.

    Article PubMed PubMed Central Google Scholar

  15. Costa e Silva VT, Gil LA Jr, Inker LA, et al. A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors. Kidney Int. 2022;101:607–14. https://doi.org/10.1016/j.kint.2021.12.010.

    Article CAS PubMed Google Scholar

  16. Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease. J Am Soc Nephrol. 2021;32:2994–3015. https://doi.org/10.1681/ASN.2021070988.

    Article CAS PubMed PubMed Central Google Scholar

  17. Oda K, Hashiguchi Y, Kimura T, et al. Performance of area under the concentration-time curve estimations of vancomycin with limited sampling by a newly developed web application. Pharm Res. 2021;38:637–46. https://doi.org/10.1007/s11095-021-03030-y.

    Article CAS PubMed Google Scholar

  18. Inker LA, Eckfeldt J, Levey AS, et al. Expressing the CKD-EPI (chronic kidney disease epidemiology collaboration) cystatin C equations for estimating GFR with standardized serum cystatin C values. Am J Kidney Dis. 2011;58:682–4. https://doi.org/10.1053/j.ajkd.2011.05.019.

    Article PubMed PubMed Central Google Scholar

  19. Stevens LA, Coresh J, Schmid CH, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis. 2008;51:395–406. https://doi.org/10.1053/j.ajkd.2007.11.018.

    Article CAS PubMed PubMed Central Google Scholar

  20. Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease. Am J Kidney Dis. 2022;79:268-288.e1. https://doi.org/10.1053/j.ajkd.2021.08.003.

    Article PubMed Google Scholar

  21. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92. https://doi.org/10.1053/j.ajkd.2008.12.034.

    Article CAS PubMed Google Scholar

  22. Horio M, Imai E, Yasuda Y, et al. GFR estimation using standardized serum cystatin C in Japan. Am J Kidney Dis. 2013;61:197–203. https://doi.org/10.1053/j.ajkd.2012.07.007.

    Article CAS PubMed Google Scholar

  23. Du Bois D, Du Bois EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition. 1989;5(5):303–11 (discussion 312–3).

    PubMed Google Scholar

  24. Ibe Y, Ishigo T, Fujii S, et al. Simulation of vancomycin exposure using trough and peak levels achieves the target area under the steady-state concentration-time curve in ICU patients. Antibiotics (Basel). 2023;12:1113. https://doi.org/10.3390/antibiotics12071113.

    Article CAS PubMed Google Scholar

  25. Baxmann AC, Ahmed MS, Marques NC, et al. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol. 2008;3:348–54. https://doi.org/10.2215/CJN.02870707.

    Article CAS PubMed PubMed Central Google Scholar

  26. Chew-Harris JS, Florkowski CM, George PM, et al. The relative effects of fat versus muscle mass on cystatin C and estimates of renal function in healthy young men. Ann Clin Biochem. 2013;50:39–46. https://doi.org/10.1258/acb.2012.011241.

    Article CAS PubMed Google Scholar

  27. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–47. https://doi.org/10.1001/jama.298.17.2038.

    Article CAS PubMed Google Scholar

  28. Stevens LA, Li S, Wang C, et al. Prevalence of CKD and comorbid illness in elderly patients in the United States: results from the Kidney Early Evaluation Program (KEEP). Am J Kidney Dis. 2010;55(Suppl 2):S23-33. https://doi.org/10.1053/j.ajkd.2009.09.035.

    Article PubMed PubMed Central Google Scholar

  29. Zhang QL, Rothenbacher D. Prevalence of chronic kidney disease in population-based studies: systematic review. BMC Public Health. 2008;8:117. https://doi.org/10.1186/1471-2458-8-117.

    Article PubMed PubMed Central Google Scholar

  30. Ballew SH, Zhou L, Surapaneni A, et al. A novel creatinine muscle index based on creatinine filtration: associations with frailty and mortality. J Am Soc Nephrol. 2023;34:495–504. https://doi.org/10.1681/ASN.0000000000000037.

    Article PubMed PubMed Central Google Scholar

  31. Chen DC, Lu K, Scherzer R, et al. Cystatin C- and creatinine-based estimated GFR differences: prevalence and predictors in the UK Biobank. Kidney Med. 2024;6: 100796. https://doi.org/10.1016/j.xkme.2024.100796.

    Article PubMed PubMed Central Google Scholar

  32. Prado CM, Purcell SA, Alish C, et al. Implications of low muscle mass across the continuum of care: a narrative review. Ann Med. 2018;50:675–93. https://doi.org/10.1080/07853890.2018.1511918.

    Article PubMed Google Scholar

  33. Kashani KB, Frazee EN, Kukrálová L, et al. Evaluating muscle mass by using markers of kidney function: development of the sarcopenia index. Crit Care Med. 2017;45:e23–9. https://doi.org/10.1097/CCM.0000000000002013.

    Article PubMed Google Scholar

  34. Lin YL, Chen SY, Lai YH, et al. Serum creatinine to cystatin C ratio predicts skeletal muscle mass and strength in patients with non-dialysis chronic kidney disease. Clin Nutr. 2020;39(8):2435–41. https://doi.org/10.1016/j.clnu.2019.10.027.

    Article CAS PubMed Google Scholar

  35. Martone AM, Bianchi L, Abete P, et al. The incidence of sarcopenia among hospitalized older patients: results from the Glisten study. J Cachexia Sarcopenia Muscle. 2017;8:907–14. https://doi.org/10.1002/jcsm.12224.

    Article PubMed PubMed Central Google Scholar

  36. Udy AA, Roberts JA, Boots RJ, et al. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49:1–16. https://doi.org/10.2165/11318140-000000000-00000.

    Article CAS PubMed Google Scholar

  37. Steinke T, Moritz S, Beck S, et al. Estimation of creatinine clearance using plasma creatinine or cystatin C: a secondary analysis of two pharmacokinetic studies in surgical ICU patients. BMC Anesthesiol. 2015;15:62. https://doi.org/10.1186/s12871-015-0043-7.

    Article CAS PubMed PubMed Central Google Scholar

  38. Ishigo T, Matsumoto K, Yoshida H, et al. Relationship between nephrotoxicity and area under the concentration-time curve of vancomycin in critically ill patients: a multicenter retrospective study. Microbiol Spectr. 2024;12(7): e0373923. https://doi.org/10.1128/spectrum.03739-23.

    Article CAS PubMed Google Scholar

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Acknowledgements

We would like to express our sincere gratitude to all the patients and medical staff who contributed to this study. Special thanks are extended to the clinical pharmacists and laboratory teams for their invaluable support in data collection and analysis.

Funding

The authors declare that no funds, grants, or other support was received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan

    Yuta Ibe, Tomoyuki Ishigo, Tomohiro Aigami, Satoshi Fujii & Masahide Fukudo

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Correspondence to Masahide Fukudo.

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Ibe, Y., Ishigo, T., Aigami, T. et al. Effect of discrepancy in estimated renal function on vancomycin area under the blood concentration–time curve: a retrospective cohort study comparing serum creatinine and serum cystatin C. Int J Clin Pharm (2025). https://doi.org/10.1007/s11096-025-01960-w

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