Estimated glomerular filtration rate based on creatinine, cystatin C, β-trace protein and β2 microglobulin in patients undergoing nontraumatic lower extremity amputation

Esben Iversen*, Anne Byriel Walls, Annamarie Petersen, Pia Søe Jensen, Thomas Kallemose, Aino Andersen, Rikke Lundsgaard Nielsen, Anne Kathrine Bengaard, Helle Gybel Juul-Larsen, Olivia Bornæs, Morten Damgaard, Ove Andersen, Juliette Tavenier, Morten Baltzer Houlind

*Corresponding author for this work

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Abstract

Aims: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, β-trace protein (BTP) and β2 microglobulin (B2M) among patients undergoing major amputation. Methods: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. Results: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (−0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. Conclusion: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

Original languageEnglish
JournalBritish Journal of Clinical Pharmacology
Volume89
Issue number6
Pages (from-to)1789-1798
ISSN0306-5251
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
This study was performed as part of the Clinical Academic Group (ACUTE‐CAG) for Recovery Capacity nominated by the Greater Copenhagen Health Science Partners (GCHSP). The study was conducted at the Department of Clinical Research, Copenhagen University Hospital Amager & Hvidovre, Hvidovre, Denmark. M.B.H. was supported by a postdoctoral fellowship from The Capital Region's Research Foundation for Health Research and the BRIDGE Translational Excellence Program (grant NNF20SA0064340). We thank all patients and staff involved in the Time to Eat study and OptiNAM trial.

Publisher Copyright:
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Keywords

  • creatinine
  • cystatin C
  • estimated glomerular filtration rate
  • nontraumatic lower extremity amputation
  • optimized prescribing
  • β-trace protein
  • β2 microglobulin

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