Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis

Objective: To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes.

Design, Setting, And Participants: Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021.

Exposures: The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR).

Main Outcomes And Measures: The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses.

Results: Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]).

Conclusions And Relevance: In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

Citing Articles

Albuminuria in Cardiovascular, Kidney, and Metabolic Disorders: A State-of-the-Art Review.

Claudel S, Verma A Circulation. 2025; 151(10):716-732.

PMID: 40063723 PMC: 11902889. DOI: 10.1161/CIRCULATIONAHA.124.071079.

Combination therapy as a new standard of care in diabetic and non-diabetic chronic kidney disease.

Neuen B, Yeung E, Rangaswami J, Vaduganathan M Nephrol Dial Transplant. 2025; 40(Supplement_1):i59-i69.

PMID: 39907542 PMC: 11795647. DOI: 10.1093/ndt/gfae258.

Upcoming drug targets for kidney protective effects in chronic kidney disease.

Nardone M, Yau K, Kugathasan L, Odutayo A, Mohsen M, Ouimet J Nephrol Dial Transplant. 2025; 40(Supplement_1):i47-i58.

PMID: 39907540 PMC: 11852282. DOI: 10.1093/ndt/gfae216.

Chronic kidney disease.

Romagnani P, Agarwal R, Chan J, Levin A, Kalyesubula R, Karam S Nat Rev Dis Primers. 2025; 11(1):8.

PMID: 39885176 DOI: 10.1038/s41572-024-00589-9.

The relationship between C-reactive protein to lymphocyte ratio and the prevalence of chronic kidney disease in US adults: a cross-sectional study.

He P, Zhang J, Tian N, Deng Y, Zhou M, Tang C Front Endocrinol (Lausanne). 2025; 15:1469750.

PMID: 39882264 PMC: 11774709. DOI: 10.3389/fendo.2024.1469750.

References

Delgado C, Baweja M, Crews D, Eneanya N, Gadegbeku C, Inker L . A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. J Am Soc Nephrol. 2021; 32(12):2994-3015. PMC: 8638402. DOI: 10.1681/ASN.2021070988. View

Porrini E, Ruggenenti P, Luis-Lima S, Carrara F, Jimenez A, de Vries A . Estimated GFR: time for a critical appraisal. Nat Rev Nephrol. 2018; 15(3):177-190. DOI: 10.1038/s41581-018-0080-9. View

Nankivell B, Nankivell L, Elder G, Gruenewald S . How unmeasured muscle mass affects estimated GFR and diagnostic inaccuracy. EClinicalMedicine. 2021; 29-30:100662. PMC: 7788434. DOI: 10.1016/j.eclinm.2020.100662. View

Levey A, Grams M, Inker L . Uses of GFR and Albuminuria Level in Acute and Chronic Kidney Disease. N Engl J Med. 2022; 386(22):2120-2128. DOI: 10.1056/NEJMra2201153. View

de Jong P, van der Velde M, Matsushita K, Coresh J, Astor B, Woodward M . Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int. 2011; 79(12):1341-52. DOI: 10.1038/ki.2010.536. View

Shin J, Chang A, Grams M, Coresh J, Ballew S, Surapaneni A . Albuminuria Testing in Hypertension and Diabetes: An Individual-Participant Data Meta-Analysis in a Global Consortium. Hypertension. 2021; 78(4):1042-1052. PMC: 8429211. DOI: 10.1161/HYPERTENSIONAHA.121.17323. View

Coresh J, Astor B, McQuillan G, Kusek J, Greene T, Van Lente F . Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis. 2002; 39(5):920-9. DOI: 10.1053/ajkd.2002.32765. View

Inker L, Schmid C, Tighiouart H, Eckfeldt J, Feldman H, Greene T . Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012; 367(1):20-9. PMC: 4398023. DOI: 10.1056/NEJMoa1114248. View

Gansevoort R, Matsushita K, van der Velde M, Astor B, Woodward M, Levey A . Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int. 2011; 80(1):93-104. PMC: 3959732. DOI: 10.1038/ki.2010.531. View

10.

Pottel H, Bjork J, Rule A, Ebert N, Eriksen B, Dubourg L . Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex. N Engl J Med. 2023; 388(4):333-343. DOI: 10.1056/NEJMoa2203769. View

11.

Levey A, de Jong P, Coresh J, El Nahas M, Astor B, Matsushita K . The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2010; 80(1):17-28. DOI: 10.1038/ki.2010.483. View

12.

Grubb A, Blirup-Jensen S, Lindstrom V, Schmidt C, Althaus H, Zegers I . First certified reference material for cystatin C in human serum ERM-DA471/IFCC. Clin Chem Lab Med. 2010; 48(11):1619-21. DOI: 10.1515/CCLM.2010.318. View

13.

Sumida K, Nadkarni G, Grams M, Sang Y, Ballew S, Coresh J . Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis : An Individual Participant-Based Meta-analysis. Ann Intern Med. 2020; 173(6):426-435. PMC: 7780415. DOI: 10.7326/M20-0529. View

14.

Ballew S, Chen Y, Daya N, Godino J, Windham B, McAdams-DeMarco M . Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis. 2016; 69(2):228-236. PMC: 5263025. DOI: 10.1053/j.ajkd.2016.08.034. View

15.

Inker L, Eneanya N, Coresh J, Tighiouart H, Wang D, Sang Y . New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med. 2021; 385(19):1737-1749. PMC: 8822996. DOI: 10.1056/NEJMoa2102953. View

16.

Resimont G, Vranken L, Pottel H, Jouret F, Krzesinski J, Cavalier E . Estimating urine albumin to creatinine ratio from protein to creatinine ratio using same day measurement: validation of equations. Clin Chem Lab Med. 2022; 60(7):1064-1072. DOI: 10.1515/cclm-2022-0049. View

17.

Delgado C, Baweja M, Crews D, Eneanya N, Gadegbeku C, Inker L . 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. 2021; 79(2):268-288.e1. DOI: 10.1053/j.ajkd.2021.08.003. View

18.

Astor B, Matsushita K, Gansevoort R, van der Velde M, Woodward M, Levey A . Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int. 2011; 79(12):1331-40. PMC: 3917543. DOI: 10.1038/ki.2010.550. View

19.

. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020; 395(10225):709-733. PMC: 7049905. DOI: 10.1016/S0140-6736(20)30045-3. View

20.

Levey A, Stevens L, Schmid C, Zhang Y, Castro 3rd A, Feldman H . A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150(9):604-12. PMC: 2763564. DOI: 10.7326/0003-4819-150-9-200905050-00006. View