Discordant Results Between Creatinine- and Cystatin C-based Equations for Estimating GFR

Pierre Delanaye; Martin Flamant; Emmanuelle Vidal-Petiot; Jonas Björk; Ulf Nyman; Anders Grubb; Stephan J L Bakker; Martin H de Borst; Marco van Londen; Laurence Derain-Dubourg; Andrew D Rule; Björn O Eriksen; Toralf Melsom; Per-Ola Sundin; Natalie Ebert; Elke Schaeffner; Magnus Hansson; Karin Littmann; Anders Larsson; Thomas Stehlé; Etienne Cavalier; Justine B Bukabau; Ernest K Sumaili; Eric Yayo; Christophe Mariat; Olivier Moranne; Anders Christensson; Antoine Lanot; Hans Pottel

doi:10.1016/j.ekir.2025.01.030

Discordant Results Between Creatinine- and Cystatin C-based Equations for Estimating GFR

Kidney Int Rep. 2025 Jan 29;10(4):1248-1259. doi: 10.1016/j.ekir.2025.01.030. eCollection 2025 Apr.

Authors

Pierre Delanaye^{1

2}, Martin Flamant³, Emmanuelle Vidal-Petiot³, Jonas Björk^{4

5}, Ulf Nyman⁶, Anders Grubb⁷, Stephan J L Bakker⁸, Martin H de Borst⁸, Marco van Londen⁸, Laurence Derain-Dubourg⁹, Andrew D Rule¹⁰, Björn O Eriksen¹¹, Toralf Melsom¹¹, Per-Ola Sundin¹², Natalie Ebert¹³, Elke Schaeffner¹³, Magnus Hansson¹⁴, Karin Littmann¹⁵, Anders Larsson¹⁶, Thomas Stehlé^{17

18}, Etienne Cavalier¹⁹, Justine B Bukabau²⁰, Ernest K Sumaili²⁰, Eric Yayo²¹, Christophe Mariat²², Olivier Moranne², Anders Christensson²³, Antoine Lanot^{24

25

26

27}, Hans Pottel²⁷

Affiliations

¹ Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium.
² Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Université de Montpellier, Nîmes, France.
³ Assistance Publique-Hôpitaux de Paris, Bichat Hospital, INSERM U1148, Université Paris Cité and Université Sorbonne Paris Nord, LVTS, Center, Paris, France.
⁴ Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden.
⁵ Clinical Studies Sweden, Forum South, Skåne University Hospital, Lund, Sweden.
⁶ Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö, Sweden.
⁷ Department of Clinical Chemistry, Skåne University Hospital, Lund University, Lund, Sweden.
⁸ Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁹ Néphrologie, Dialyse, Hypertension et Exploration Fonctionnelle Rénale, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
¹⁰ Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.
¹¹ Section of Nephrology, University Hospital of North Norway and Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
¹² Karla Healthcare Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
¹³ Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany.
¹⁴ Function Area Clinical Chemistry, Karolinska University Laboratory, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden.
¹⁵ Division of Medicine Huddinge (MedH), Karolinska Institute, Stockholm, Sweden.
¹⁶ Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
¹⁷ Université Paris Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale, Créteil, France.
¹⁸ Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Fédération Hospitalo-Universitaire, Innovative therapy for immune disorders, Créteil, France.
¹⁹ Department of Clinical Chemistry, University of Liège, CHU Sart Tilman, Liège, Belgium.
²⁰ Renal Unit, Department of Internal Medicine, Kinshasa University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
²¹ Département de Biochimie, UFR Sciences Pharmaceutiques et Biologiques, Université Felix Houphouët Boigny, Abidjan, Côte d'Ivoire.
²² Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord, CHU de Saint-Etienne, France.
²³ Department of Nephrology, Skåne University Hospital, Lund University, Malmö, Sweden.
²⁴ Normandie Université, Unicaen, CHU de Caen Normandie, Néphrologie, Côte de Nacre Caen, France.
²⁵ Normandie Université, Unicaen, UFR de médecine, Caen, France.
²⁶ ANTICIPE" U1086 INSERM-UCN, Center François Baclesse, Caen, France.
²⁷ Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.

Abstract

Introduction: Discordant results between cystatin C and creatinine in estimating glomerular filtration rate (GFR) are an important medical issue. However, the equation that should be used when GFR estimates are discordant remains unclear.

Methods: This cross-sectional analysis included 15,485 participants with GFR measured by the clearance of an exogenous marker, serum creatinine, and cystatin C. We studied the proportion of discordant results defined as an absolute (> 15 ml/min per 1.73 m²) or relative (> 20%) difference between creatinine-based estimated GFR (eGFR, eGFR_crea) and cystatin C-based eGFR (eGFR_cys) using different equations (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], European Kidney Function Consortium [EKFC], and reexpressed Lund-Malmö [r-LMR]). We also researched for the best estimating equations to be used in subjects with concordant or discordant results to estimate measured GFR (mGFR).

Results: In the total cohort, the proportion of subjects with discordant results (absolute or relative) was larger for CKD-EPI (35.1 and 40.6%) than for EKFC (21.9 and 31.7%) or r-LMR (22.8 and 32.8%) equations. Among discrepant results, the proportion of eGFR_cys < eGFR_crea was significantly higher than the proportion of eGFR_crea < eGFR_cys for the CKD-EPI equations, whereas the occurrence of discrepancy was similar in the 2 discrepant groups for EKFC or r-LMR. For the EKFC and r-LMR equations, but not for the CKD-EPI, the equation combining creatinine and cystatin C was consistently the closest to the mGFR in the discrepant groups.

Conclusion: Based on the lower discrepancy proportion, better balance between eGFR_crea and eGFR_cys, and better concordance with mGFR, the EKFC, and r-LMR equations should be preferred over the CKD-EPI to estimate GFR.

Keywords: creatinine; cystatin C; glomerular filtration rate.