Test accuracy of glomerular filtration rate estimation with creatinine and cystatin C in adults with moderate chronic kidney disease: prospective cohort study
Lamb, Edmund J Barratt, Jonathan Brettell, Elizabeth Ann Cockwell, Paul Dalton, R Neil Deeks, Jonathan James Eaglestone, Gillian Kalra, Philip Khunti, Kamlesh Loud, Fiona C
Lamb, Edmund J
Barratt, Jonathan
Brettell, Elizabeth Ann
Cockwell, Paul
Dalton, R Neil
Deeks, Jonathan James
Eaglestone, Gillian
Kalra, Philip
Khunti, Kamlesh
Loud, Fiona C
Affiliation
East Kent Hospitals University NHS Foundation Trust; University of Leicester; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; Guy's and St Thomas' NHS Foundation Trust; Northern Care Alliance NHS Foundation Trust; Kidney Care UK; University of Kent; University of Nottingham; University of Leeds; University of Warwick; University Hospitals of Derby and Burton NHS Foundation Trust
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Publication date
2026-01-21
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Abstract
Objective: To study the performance of two contemporary sets of estimating equations for glomerular filtration rate, published by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) and EKFC (European Kidney Function Consortium) that include one (creatinine or cystatin C only) and combined (creatinine and cystatin C) biomarkers, to assess their accuracy in a population with moderate chronic kidney disease.
Design: Prospective cohort study.
Setting: Primary, secondary, and tertiary care in six centres in England. Participants were recruited from April 2014 to January 2017.
Participants: 1167 adults, aged ≥18 years, with moderate chronic kidney disease (estimated glomerular filtration rate 30-59 mL/min/1.73 m2 sustained over at least three months before recruitment).
Main outcome measures: Accuracy of estimating equations CKD-EPIcreatinine, CKD-EPIcystatin, CKD-EPIcreatinine-cystatin, EKFCcreatinine, EKFCcystatin, and EKFCcreatinine-cystatin compared with measured glomerular filtration rate (iohexol clearance). Remodelled 2021 versions of the CKD-EPI equations were also studied. Accuracy was expressed as P30 (percentage of estimates within 30% of measured glomerular filtration rate).
Results: Median age was 67.5 years, 58.3% of patients were men, 86.9% were white participants, and 27.8% had diabetes. Median measured glomerular filtration rate was 47.0 mL/min/1.73 m2; 57.0% of participants had albuminuria. Test calibration critically affected measurement of cystatin C. After recalibration of cystatin C, P30 values were 90.2% (CKD-EPIcreatinine), 89.5% (CKD-EPIcystatin), 94.9% (CKD-EPIcreatinine-cystatin), 88.0% (CKD-EPI(2021)creatinine), 94.9% (CKD-EPI(2021)creatinine-cystatin), 89.4% (EKFCcreatinine), 91.0% (EKFCcystatin), and 94.9% (EKFCcreatinine-cystatin). Creatinine based equations showed varying bias depending on the glomerular filtration rate level; inclusion of cystatin C in the equations improved this effect. Differences in accuracy in age, sex, and glomerular filtration rate level subgroups varied by equation. Equations combining creatinine and cystatin performed equally across age, sex, diabetes status, albuminuria status, and body mass index categories.
Conclusions: The CKD-EPIcreatinine equation had acceptable accuracy in a white population in England with moderate chronic kidney disease. Combined dual biomarker equations showed higher accuracy than the CKD-EPIcreatinine equation and their equivalent creatinine only equations. Further research is needed to determine the most accurate equation to use in people of black and South Asian origin living in England.
Citation
Lamb EJ, Barratt J, Brettell EA, Cockwell P, Dalton RN, Deeks JJ, Eaglestone G, Kalra P, Khunti K, Loud FC, Mead PA, Ottridge R, Pellatt-Higgins T, Potter A, Rowe C, Scandrett K, Sharpe C, Shinkins B, Sitch AJ, Smith A, Stevens PE, Sutton AJ, Taal M. Test accuracy of glomerular filtration rate estimation with creatinine and cystatin C in adults with moderate chronic kidney disease: prospective cohort study. BMJ Med. 2026 Jan 21;5(1):e001827. doi: 10.1136/bmjmed-2025-001827.
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Article