Skip to main content
Top
Published in:

Open Access 13-02-2024 | IM - ORIGINAL

New race-free creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate and association with cardiovascular mortality in the AtheroGene study

Authors: George Ntaios, Jan Brederecke, Francisco M. Ojeda, Tanja Zeller, Stefan Blankenberg, Renate B. Schnabel

Published in: Internal and Emergency Medicine | Issue 3/2024

Login to get access

Abstract

Renal function is associated with cardiovascular outcomes and mortality. Among equations used to eGFR, CKD–EPI equations show more accurate association with cardiovascular risk and mortality than MDRD. Recently, new CKD–EPI equations were proposed which do not include race and would be considered sufficiently accurate to estimate eGFR in clinical practice. It is unknown if these new race-free equations are comparably well associated with cardiovascular outcomes in high-risk individuals. The analysis was performed in the AtheroGene Study cohort including patients at high cardiovascular risk. eGFR was determined using the established as well as the recently developed formulas which are calculated without the otherwise existing coefficient for black race. The outcome was cardiovascular death. Analyses included Cox-proportional hazard regression and area-under-the-curve calculation. The analysis included 2089 patients followed up for a median of 3.8 years with a maximum of 6.9 years, corresponding to an overall period of 7701 patient-years. Cardiovascular death occurred in 93 (4.45%), corresponding to an annualized rate of 1.2/100 person-years. In all Cox regression analyses, the estimated adjusted GFR was an independent predictor of cardiovascular death. The equations which included cystatin C showed higher C-index compared to those which did not include cystatin C (0.75–0.76 vs. 0.71, respectively). The equations for the estimation of eGFR which include cystatin C are better associated with cardiovascular death compared to the race-free equations which include only creatinine. This finding adds on the related literature which supports the elimination of race in GFR-estimating equations, and promotion of the use of cystatin C.
Appendix
Available only for authorised users
Literature
1.
go back to reference Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D, Modification of Diet in Renal Disease Study Group (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130:461–470CrossRefPubMed Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D, Modification of Diet in Renal Disease Study Group (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med 130:461–470CrossRefPubMed
2.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentral
3.
go back to reference Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T et al (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29CrossRefPubMedPubMedCentral Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH, Feldman HI, Greene T et al (2012) Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 367:20–29CrossRefPubMedPubMedCentral
5.
go back to reference Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y et al (2021) New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med 385:1737–1749CrossRefPubMedPubMedCentral Inker LA, Eneanya ND, Coresh J, Tighiouart H, Wang D, Sang Y et al (2021) New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med 385:1737–1749CrossRefPubMedPubMedCentral
6.
go back to reference Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305CrossRefPubMed Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305CrossRefPubMed
7.
go back to reference Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L et al (2019) ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J 41:111–188 Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L et al (2019) ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J 41:111–188
8.
go back to reference Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L et al (2003) Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 349:1605–1613CrossRefPubMed Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L et al (2003) Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med 349:1605–1613CrossRefPubMed
9.
go back to reference Keller T, Messow CM, Lubos E, Nicaud V, Wild PS, Rupprecht HJ et al (2009) Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study. Eur Heart J 30:314–320CrossRefPubMed Keller T, Messow CM, Lubos E, Nicaud V, Wild PS, Rupprecht HJ et al (2009) Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study. Eur Heart J 30:314–320CrossRefPubMed
10.
go back to reference Kragelund C, Gronning B, Kober L, Hildebrandt P, Steffensen R (2005) N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med 352:666–675CrossRefPubMed Kragelund C, Gronning B, Kober L, Hildebrandt P, Steffensen R (2005) N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. N Engl J Med 352:666–675CrossRefPubMed
11.
go back to reference Blanche P, Dartigues JF, Jacqmin-Gadda H (2013) Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med 32:5381–5397CrossRefPubMed Blanche P, Dartigues JF, Jacqmin-Gadda H (2013) Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med 32:5381–5397CrossRefPubMed
13.
go back to reference Lees JS, Welsh CE, Celis-Morales CA, Mackay D, Lewsey J, Gray SR et al (2019) Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease. Nat Med 25:1753–1760CrossRefPubMedPubMedCentral Lees JS, Welsh CE, Celis-Morales CA, Mackay D, Lewsey J, Gray SR et al (2019) Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease. Nat Med 25:1753–1760CrossRefPubMedPubMedCentral
14.
go back to reference Gutierrez OM, Sang Y, Grams ME, Ballew SH, Surapaneni A, Matsushita K et al (2022) Association of estimated GFR calculated using race-free equations with kidney failure and mortality by black vs non-black race. JAMA 327:2306–2316CrossRefPubMedPubMedCentral Gutierrez OM, Sang Y, Grams ME, Ballew SH, Surapaneni A, Matsushita K et al (2022) Association of estimated GFR calculated using race-free equations with kidney failure and mortality by black vs non-black race. JAMA 327:2306–2316CrossRefPubMedPubMedCentral
15.
go back to reference Hsu CY, Yang W, Parikh RV, Anderson AH, Chen TK, Cohen DL et al (2021) race, genetic ancestry, and estimating kidney function in CKD. N Engl J Med 385:1750–1760CrossRefPubMedPubMedCentral Hsu CY, Yang W, Parikh RV, Anderson AH, Chen TK, Cohen DL et al (2021) race, genetic ancestry, and estimating kidney function in CKD. N Engl J Med 385:1750–1760CrossRefPubMedPubMedCentral
16.
go back to reference Bjork J, Nyman U, Berg U, Delanaye P, Dubourg L, Goffin K et al (2019) Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children. Pediatr Nephrol 34:1087–1098CrossRefPubMed Bjork J, Nyman U, Berg U, Delanaye P, Dubourg L, Goffin K et al (2019) Validation of standardized creatinine and cystatin C GFR estimating equations in a large multicentre European cohort of children. Pediatr Nephrol 34:1087–1098CrossRefPubMed
17.
go back to reference Schaeffner ES, Ebert N, Delanaye P, Frei U, Gaedeke J, Jakob O et al (2012) Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med 157:471–481CrossRefPubMed Schaeffner ES, Ebert N, Delanaye P, Frei U, Gaedeke J, Jakob O et al (2012) Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med 157:471–481CrossRefPubMed
18.
go back to reference Segarra A, de la Torre J, Ramos N, Quiroz A, Garjau M, Torres I et al (2011) Assessing glomerular filtration rate in hospitalized patients: a comparison between CKD–EPI and four cystatin C-based equations. Clin J Am Soc Nephrol 6:2411–2420CrossRefPubMedPubMedCentral Segarra A, de la Torre J, Ramos N, Quiroz A, Garjau M, Torres I et al (2011) Assessing glomerular filtration rate in hospitalized patients: a comparison between CKD–EPI and four cystatin C-based equations. Clin J Am Soc Nephrol 6:2411–2420CrossRefPubMedPubMedCentral
19.
go back to reference Ebert N, Shlipak MG (2020) Cystatin C is ready for clinical use. Curr Opin Nephrol Hypertens 29:591–598CrossRefPubMed Ebert N, Shlipak MG (2020) Cystatin C is ready for clinical use. Curr Opin Nephrol Hypertens 29:591–598CrossRefPubMed
20.
go back to reference Delgado C, Baweja M, Crews DC, Eneanya ND, Gadegbeku CA, Inker LA et al (2022) A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease. Am J Kidney Dis 79:268-288e1CrossRefPubMed Delgado C, Baweja M, Crews DC, Eneanya ND, Gadegbeku CA, Inker LA et al (2022) A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease. Am J Kidney Dis 79:268-288e1CrossRefPubMed
21.
go back to reference Blirup-Jensen S, Grubb A, Lindstrom V, Schmidt C, Althaus H (2008) Standardization of cystatin C: development of primary and secondary reference preparations. Scand J Clin Lab Invest Suppl 241:67–70CrossRefPubMed Blirup-Jensen S, Grubb A, Lindstrom V, Schmidt C, Althaus H (2008) Standardization of cystatin C: development of primary and secondary reference preparations. Scand J Clin Lab Invest Suppl 241:67–70CrossRefPubMed
22.
go back to reference Mohottige D, Purnell TS, Boulware LE (2023) Redressing the harms of race-based kidney function estimation. JAMA 329:881–882CrossRefPubMed Mohottige D, Purnell TS, Boulware LE (2023) Redressing the harms of race-based kidney function estimation. JAMA 329:881–882CrossRefPubMed
Metadata
Title
New race-free creatinine- and cystatin C-based equations for the estimation of glomerular filtration rate and association with cardiovascular mortality in the AtheroGene study
Authors
George Ntaios
Jan Brederecke
Francisco M. Ojeda
Tanja Zeller
Stefan Blankenberg
Renate B. Schnabel
Publication date
13-02-2024
Publisher
Springer International Publishing
Published in
Internal and Emergency Medicine / Issue 3/2024
Print ISSN: 1828-0447
Electronic ISSN: 1970-9366
DOI
https://doi.org/10.1007/s11739-023-03529-9

Elevate your expertise in aplastic anemia (Link opens in a new window)

Transform the way you care for your patients with aplastic anemia with our 3-module series using real-world case studies and expert insights. Discover why early diagnosis matters, explore the benefits and risks of current treatments, and develop tailored approaches for complex cases. 

Supported by:
  • Pfizer
Developed by: Springer Healthcare IME
Learn more

Keynote series | Spotlight on menopause

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.   

Prof. Martha Hickey
Dr. Claudia Barth
Dr. Samar El Khoudary
Developed by: Springer Medicine
Watch now
Video