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Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex
Hans Pottel1, Jonas Björk1, Andrew D Rule1
1From the Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk (H.P.), and the Departments of Clinical Chemistry (E.C.) and Nephrology-Dialysis-Transplantation (P.D.), University of Liège, Centre Hospitalier Universitaire du Sart-Tilman, Liège - all in Belgium; the Division of Occupational and Environmental Medicine, Lund University (J.B., A.Å.), Clinical Studies Sweden, Forum South (J.B., A.Å.), and the Department of Clinical Chemistry (A.G.), Skåne University Hospital, Lund, the Function Area Clinical Chemistry, Karolinska University Laboratory, Karolinska University Hospital Huddinge, and Department of Laboratory Medicine, Stockholm (M.H.), the Division of Clinical Chemistry, Huddinge (K.L.), the Department of Geriatrics, School Department of Laboratory Medicine, Karolinska Institutet of Medical Sciences, Örebro University, Örebro (P.-O.S.), the Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala (A.L.), and the Department of Translational Medicine, Division of Medical Radiology, Lund University, Malmö (U.N.) - all in Sweden; the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (A.D.R.); Charité Universitätsmedizin Berlin, Institute of Public Health, Berlin, Germany (N.E., E.S.); the Section of Nephrology, University Hospital of North Norway and Metabolic and Renal Research Group, Universitetet i Tromsø the Arctic University of Norway, Tromsø, Norway (B.O.E., T.M.); Service de Néphrologie, Dialyse, Hypertension et Explorations Fonctionnelles Rénales, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon (L.D.), Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, and Université de Paris, INSERM Unité 1149 (E.V.-P.), and AP-HP, Bichat Hospital, and Université de Paris, Unité Mixte de Recherche S1138, Cordeliers Research Center (M.F.), Paris, Service de Néphrologie, Dialyse et Transplantations Rénales, Hôpital Nord, Centre Hospitalier Universitaire de Saint-Étienne, Saint-Étienne (C.M.), and the Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes (P.D.) - all in France; Clinical Biochemistry, East Kent Hospitals University NHS Foundation Trust, Canterbury, United Kingdom (E.J.L.); the Renal Unit, Department of Internal Medicine, Kinshasa University Hospital, University of Kinshasa, Kinshasa, Democratic Republic of Congo (J.B.B., E.K.S.); and the Département de Biochimie, Unité de Formation et de Recherche Sciences Pharmaceutiques et Biologiques, Université Felix Houphouët Boigny, Abidjan, Ivory Coast (E.Y., D.M.).
Background:
The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown.
Methods:
We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.
Results:
On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.
Conclusions:
The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.).
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