Several equations exist for estimating glomerular filtration rate (GFR) in children and adults, but they have some well-known limitations, such as yielding implausible GFR estimates during the transition from adolescence to adulthood. This article describes the development and validation of a modified full age spectrum equation for estimating kidney function.
Abstract
Background:
The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)–based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low.
Objective:
To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations.
Design:
Cross-sectional analysis with separate pooled data sets for development and validation.
Setting:
Research and clinical studies (n = 13) with measured GFR available.
Patients:
11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set).
Measurements:
Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR.
Results:
The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (−1.2 mL/min/1.73 m2 [95% CI, −2.7 to 0.0 mL/min/1.73 m2] in children and −0.9 mL/min/1.73 m2 [CI, −1.2 to −0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations.
Limitation:
No Black patients were included.
Conclusion:
The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels.
Primary Funding Source:
Swedish Research Council (Vetenskapsrådet).
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Author, Article, and Disclosure Information
Hans Pottel,
KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium (H.P.)
Lund University and Skåne University Hospital, Lund, Sweden (J.B., A.Å.)
Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), Paris Descartes University, INSERM U1151-CNRS UMR8253, Paris, France (M.C.)
CHU de Bordeaux, Université de Bordeaux, CNRS-UMR 5164 Immuno ConcEpT, Bordeaux, France (L.C.)
Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany (N.E., E.S.)
UiT The Arctic University of Norway, Tromsö, Norway (B.O.E., T.M.)
Evelina London Children's Hospital, London, United Kingdom (R.N.D.)
Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France (L.D.)
Assistance Publique Hôpitaux de Paris (AP-HP), Paris, France (F.G.)
Clermont-Ferrand University Hospital, Clermont-Ferrand, France (C.G.)
Skåne University Hospital and Lund University, Lund, Sweden (A.G.)
CHU Nantes, Nantes University, Nantes, France (L.J.)
Karolinska University Hospital Huddinge and Karolinska Institute, Stockholm, Sweden (M.H.)
CHU Rangueil, INSERM U1043, IFR–BMT, University Paul Sabatier, Toulouse, France (N.K.)
East Kent Hospitals University NHS Foundation Trust, Canterbury, United Kingdom (E.J.L.)
Hôpital Necker, Assistance Publique Hôpitaux de Paris (AP-HP)and Université Paris Descartes, Paris, France (C.L.)
Karolinska Institute, Huddinge, Sweden (K.L.)
Hôpital Nord, CHU de Saint-Etienne, Saint-Etienne, France (C.M.)
Hôpital Michallon, CHU Grenoble-Alpes, La Tronche, France (L.R.)
Mayo Clinic, Rochester, Minnesota (A.D.R., S.T.)
Örebro University, Örebro, Sweden (P.S.)
Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (A.B.)
Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden (U.B., K.Å.)
Mestrado em Ciências da Saúde–Universidade Caxias do Sul Foundation CAPES, Caxias do Sul, Brazil (L.S.)
Skåne University Hospital, Lund, Sweden; Uppsala University, Uppsala, Sweden (A.L.)
Lund University, Malmö, Sweden (U.N.)
University of Liège (ULg CHU), CHU Sart Tilman, Liège, Belgium, and Hôpital Universitaire Carémeau, Nîmes, France (P.D.)
Note: Drs Pottel, Björk, Courbebaisse, Ebert, Eriksen, Dubourg, Gaillard, Grubb, Lamb, Mariat, Melsom, Rule, Schaeffner, Bökenkamp, Selistre, Nyman, and Delanaye are members of the EKFC.
Disclaimer: The CRIC Study was conducted by the CRIC investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The CRIC data reported here were supplied by the NIDDK Central Repository. This manuscript was not prepared in collaboration with the CRIC investigators and does not necessarily reflect the opinions or views of the CRIC investigators, NIDDK Central Repository, or NIDDK.
Grant Support: By grant 2019-00198 from the Swedish Research Council (Vetenskapsrådet).
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-4366.
Reproducible Research Statement: Study protocol and statistical code: Available from Dr. Pottel (e-mail, hans.
Corresponding Author: Hans Pottel, PhD, Department of Primary Care and Public Health at Kulak, KU Leuven Kulak, Etienne Sabbelaan 53, 8500 Kortrijk, Belgium; e-mail, Hans.
Current Author Addresses: Dr. Pottel: Department of Primary Care and Public Health at Kulak, KU Leuven Kulak, Etienne Sabbelaan 53, 8500 Kortrijk, Belgium.
Dr. Björk: Lund University, Box 117, SE-221 00, Lund, Sweden.
Dr. Courbebaisse: Service de Physiologie-Explorations Fonctionnelles Rénales Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France.
Dr. Couzi: CHU de Bordeaux, Nephrologie-Transplantation-Dialyse, Hôpital Pellegrin, Université de Bordeaux, place Amélie Raba Léon, 33076 Bordeaux, France.
Dr. Ebert: Institute of Public Health, Charité Universitätsmedizin Berlin, Luisenstrasse 57, 10117 Berlin, Germany.
Drs. Eriksen and Melsom: University Hospital of North Norway (UNN), Breivika, 9038 Tromsø, Norway.
Dr. Dalton: The Wellchild Laboratory, Evelina London Children's Hospital, London SE1 7EH, United Kingdom.
Dr. Dubourg: Exploration Fonctionnelle Rénale Pavillon P, Hôpital Edouard Herriot, 5 place d'Arsonval, 69437 Lyon cedex 03, France.
Dr. Gaillard: Renal Transplantation Department, Assistance Publique–Hôpitaux de Paris (AP-HP), Hopital Bichat, 46 rue Henri Huchard, 75018 Paris, France.
Dr. Garrouste: Department of Nephrology and Transplantation, Montpied Hospital, 58 rue Montalembert, 63001 Clermont Ferrand, France.
Dr. Grubb: Department of Clinical Chemistry and Pharmacology, Laboratory Medicine, Lund University, SE-22185 Lund, Sweden.
Dr. Jacquemont: Service de Néphrologie et Immunologie clinique, CHU de Nantes, 30 boulevard Jean Monnet, 44093 Nantes Cedex 1, France.
Dr. Hansson: Department of Clinical Chemistry, C1:74 Huddinge, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
Dr. Kamar: Department of Nephrology and Organ Transplantation, CHU Rangueil, 1 avenue J.Poulhès, TSA 50032, 31059 Toulouse Cedex 9, France.
Dr. Lamb: Clinical Biochemistry, Pathology, East Kent Hospitals University NHS Foundation Trust, Canterbury, Kent CT1 3NG, United Kingdom.
Dr. Legendre: Transplantation rénale, Hôpital Necker, 145 rue de sevres, 75015 Paris, France.
Dr. Littmann: Department of Medicine Huddinge, Karolinska Institutet, C2:91 Karolinska University Hospital, SE-141 52 Huddinge, Sweden.
Dr. Mariat: Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord, CHU de Saint-Etienne, 25 Boulevard Pasteur, 42055, Saint-Etienne Cedex 2, France.
Dr. Rostaing: Service de Néphrologie, Hémodialyse, Aphérèses et Transplantation Rénale, Hôpital Michallon, Centre Hospitalier Universitaire Grenoble-Alpes, Boulevard de la Chantourne, 38700 La Tronche, France.
Drs. Rule and Turner: Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905.
Dr. Schaeffner: Institute of Public Health, Charité Universitätsmedizin Berlin, Luisenstrasse 57, 10117 Berlin, Germany.
Dr. Sundin: Geriatriska kliniken, Universitetssjukhuset Örebro, 701 85 Örebro, Sweden.
Dr. Bökenkamp: de Boelelaan 1112, Amsterdam 1081 HV, the Netherlands.
Dr. Berg: Department of Clinical Science, Intervention and Technology, Division of Pediatrics, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 14186, Sweden.
Dr. Åsling-Monemi: Barnnjursektionen K 88, Astrid Lindgrens Barnsjukhus, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
Dr. Selistre: Universidade de Caxias do Sul, Rua Francisco Getúlio Vargas, 1130–CEP 95070-560 Caxias do Sul, RS, Brazil.
Dr. Åkesson: Skåne University Hospital, Clinical Studies Sweden–Forum South, Remissgatan 4, SE-221 85 Lund, Sweden.
Dr. Larsson: Clinical Chemistry and Pharmacology, Entrance 61, 2nd floor, Akademiska Hospital, SE-751 85 Uppsala, Sweden.
Dr. Nyman: Östra Vallgatan 41, SE-223 61 Lund, Sweden.
Dr. Delanaye: Service de Dialyse, CHU Sart Tilman, 4000 Liège, Belgium.
Author Contributions: Conception and design: H. Pottel, J. Björk, U. Nyman, P. Delanaye.
Analysis and interpretation of the data: H. Pottel, J. Björk, B.O. Eriksen, L. Dubourg, A. Grubb, E.J. Lamb, C. Mariat, T. Melsom, L. Rostaing, A.D. Rule, A. Bökenkamp, U. Berg, K. Åsling-Monemi, A. Larsson, U. Nyman, P. Delanaye.
Drafting of the article: H. Pottel, J. Björk, U. Nyman, P. Delanaye.
Critical revision for important intellectual content: H. Pottel, J. Björk, N. Ebert, B.O. Eriksen, R.N. Dalton, L. Dubourg, F. Gaillard, M. Hansson, E.J. Lamb, K. Littmann, C. Mariat, T. Melsom, L. Rostaing, A.D. Rule, E. Schaeffner, P.O. Sundin, A. Bökenkamp, U. Berg, K. Åsling-Monemi, Anna Åkesson, A. Larsson, U. Nyman, P. Delanaye.
Final approval of the article: H. Pottel, J. Björk, M. Courbebaisse, L. Couzi, N. Ebert, B.O. Eriksen, R.N. Dalton, L. Dubourg, F. Gaillard, C. Garrouste, A. Grubb, L. Jacquemont, M. Hansson, N. Kamar, E.J. Lamb, C.M. Legendre, K. Littmann, C. Mariat, T. Melsom, L. Rostaing, A.D. Rule, E. Schaeffner, P.O. Sundin, S. Turner, A. Bökenkamp, U. Berg, K. Åsling-Monemi, L. Selistre, A. Åkesson, A. Larsson, U. Nyman, P. Delanaye.
Provision of study materials or patients: N. Ebert, B.O. Eriksen, R.N. Dalton, L. Dubourg, F. Gaillard, A. Grubb, E.J. Lamb, A.D. Rule, A. Bökenkamp, K. Åsling-Monemi, L. Selistre, A. Larsson.
Statistical expertise: H. Pottel, J. Björk, B.O. Eriksen, A.D. Rule, P. Delanaye.
Obtaining of funding: J. Björk, B.O. Eriksen.
Administrative, technical, or logistic support: A. Åkesson, A. Larsson.
Collection and assembly of data: H. Pottel, J. Björk, M. Courbebaisse, L. Couzi, N. Ebert, B.O. Eriksen, R.N. Dalton, L. Dubourg, F. Gaillard, C. Garrouste, A. Grubb, L. Jacquemont, M. Hansson, N. Kamar, E.J. Lamb, C. Legendre, K. Littmann, C. Mariat, T. Melsom, L. Rostaing, A.D. Rule, E. Schaeffner, P.O. Sundin, S. Turner, A. Bökenkamp, U. Berg, K. Åsling-Monemi, L. Selistre, A. Larsson, U. Nyman, P. Delanaye.
This article was published at Annals.org on 10 November 2020.
* Drs. Pottel and Björk share first authorship.
† Drs. Nyman and Delanaye share last/senior authorship.
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