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Cited by 396Chronic Kidney Disease and DiabetesAcute Kidney Injury ResearchDialysis and Renal Disease Management

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

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Writing Group for the CKD Prognosis Consortium, Appel, Lawrence J, Grams, Morgan, Woodward, Mark, Harris, Katie, Arima, Hisatomi, Chalmers, John, Yatsuya, Hiroshi +310 more·2023·JAMA
DOI 10.1001/jama.2023.17002PMC PMC10548311
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Abstract

Importance: Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. 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 m 2 (SD, 22 mL/min/1.73 m 2 ) 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 m 2 (SD, 22 mL/min/1.73 m 2 ) 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 m 2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m 2 (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.

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  • A large patient-level meta-analysis showed that estimated glomerular filtration rate (eGFR) decline and albuminuria are both associated with increased risk of adverse CV and renal events in the general population.

    “A large patient-level meta-analysis showed that estimated glomerular filtration rate (eGFR) decline and albuminuria are both associated with increased risk of adverse CV and renal events in the general population78”

    From Incretin-based therapies for the treatment of obesity-related diseases (2024) · cites this paper as [78]

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  1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3(1):1-150.

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Writing Group for the CKD Prognosis Consortium, Appel, L. J., Grams, M., Woodward, M., Harris, K., Arima, H., Chalmers, J., Yatsuya, H., Tamakoshi, K., Li, Y., Coresh, J., Sang, Y., Matsushita, K., Polkinghorne, K., Chadban, S., Levin, A., Djurdjev, O., Tang, M., Zhang, L., Wang, F., Wang, J., Zhao, M.-H., Schaeffner, E., Ebert, N., Mielke, N., Tonelli, M., Lloyd, A., Sacks, F., Shlipak, M. G., Bansal, N., Sarnak, M., Yamagishi, K., Muraki, I., Shimizu, Y., Iso, H., Fukagawa, M., Maruyama, S., Hamano, T., Fujii, N., Imaizumi, T., Alencar De Pinho, N., Metzger, M., Stengel, B., Hamroun, A., Massy, Z., Jafar, T. H., Jehan, I., Hatcher, J., Chaturvedi, N., Poulter, N., Wheeler, D. C., Landray, M., Anderson, A., Chen, J., Lash, J., Taliercio, J., Yang, P. (., Tuttle, K., Alicic, R., Nicholas, S., Shen, J., Schöttker, B., Stocker, H., Rothenbacher, D., Brenner, H., Levy, D., Hwang, S.-J., Schneider, M. P., Köttgen, A., Meiselbach, H., Eckardt, K.-U., Chang, A. R., Green, J. A., Kirchner, H. L., Singh, G., Sawhney, S., Black, C., Wilde, K., Marks, A., Bell, S., Siddiqui, M., Palmer, C., Pearson, E., Miyazaki, M., Nakayama, M., Yamamoto, T., Yamada, G., Ito, S., Cirillo, M., Wang, A. Y.-M., Wu, H. H.-L., Cheung, H. C., Ngai, V., Tak, T. K., Garg, A. X., McArthur, E., Young, A., Jha, V., Yadav, A. K., Kumar, V., Carson, A. P., Young, B. A., Diamantidis, C., Min, Y.-I., Purnell, T. S., Ishikawa, S., Mieno, M., Yamagata, K., Iseki, K., Asahi, K., Konta, T., Lee, B. J., Brunskill, N. J., Gray, L., Major, R., Medcalf, J., Chodick, G., Melzer Cohen, C., Wetzels, J. F., Blankestijn, P. J., van Zuilen, A. D., Inker, L. A., Levey, A. S., Ix, J., de Boer, I., Katz, R., Kronenberg, F., Kollerits, B., Ritz, E., Nitsch, D., Nadkarni, G. N., Chan, L., Bottinger, E. P., Oh, W., Liu, Z., Zhang, H., Zhang, L., Valdivielso, J. M., Bermudez-Lopez, M., Bozic, M., Caus, M., Diaz-Tocados, J. M., Stengel, B., Miura, K., Ueshima, H., Okayama, A., Kadota, A., Okamura, T., Sola, L., Ferreiro, A., Santiago, J., Rios, P., Gadola, L., Silvariño, R., Ohkubo, T., Satoh, M., Metoki, H., Kikuya, M., Ciemins, E., Mohl, J., Nelson, R. G., Hanson, R. L., Looker, H. C., Gansevoort, R. T., Kieneker, L. M., Bakker, S. J., Moranne, O., Couchoud, C., Shepherd, D., Jassal, S. K., Bergstrom, J., Kovesdy, C. P., Sumida, K., Shrestha, P., Gutierrez, O., Cheung, K., Muntner, P., Ilori, T., Pena, M., Heerspink, H. J., Fu, E. L., Elinder, C.-G., Barany, P., Carrero, J. J., Evans, M., Sabanayagam, C., Cheng, C.-Y., Wong, T. Y., Yuen, C. C. C., Herrington, W., Staplin, N., Landray, M. J., Baigent, C., Kalra, P., Chinnadurai, R., Green, D., Sinha, S., Ritchie, J., Visseren, F. L., Burger, P., Emmelot, M., van Welzen, B., John, O., Gummidi, B., Ghosh, A., Naimark, D., Tangri, N., Wen, C.-P., Tsai, M.-K., Ueno, Y., Watanabe, M., Ichikawa, K., Mirbolouk, M., Azizi, F., Hadaegh, F., Hosseinpanah, F., Shi, W., Arking, D., Ärnlöv, J., Larsson, A., Giedraitis, V., Mark, P., Traynor, J., Sullivan, M., Lees, J., Yang, J. W., Shin, J. I., Lee, J. Y., Kim, J. S., Bilo, H. J., van Dijk, P., Edens, M., Dille, J., Ballew, S. H., Carrero, J.-J., Grams, M. E., Chen, J., Surapaneni, A., Grams, M. E., Coresh, J., Matsushita, K., Ballew, S. H., Sang, Y., Surapaneni, A., Alencar de Pinho, N., Anderson, A., Appel, L. J., Ärnlöv, J., Azizi, F., Bansal, N., Bell, S., Bilo, H. J. G., Brunskill, N. J., Carrero, J. J., Chadban, S., Chalmers, J., Chen, J., Ciemins, E., Cirillo, M., Ebert, N., Evans, M., Ferreiro, A., Fu, E. L., Fukagawa, M., Green, J. A., Gutierrez, O. M., Herrington, W. G., Hwang, S.-J., Inker, L. A., Iseki, K., Jafar, T., Jassal, S. K., Jha, V., Kadota, A., Katz, R., Köttgen, A., Konta, T., Kronenberg, F., Lee, B. J., Lees, J., Levin, A., Looker, H. C., Major, R., Melzer Cohen, C., Mieno, M., Miyazaki, M., Moranne, O., Muraki, I., Naimark, D., Nitsch, D., Oh, W., Pena, M., Purnell, T. S., Sabanayagam, C., Satoh, M., Sawhney, S., Schaeffner, E., Schöttker, B., Shen, J. I., Shlipak, M. G., Sinha, S., Stengel, B., Sumida, K., Tonelli, M., Valdivielso, J. M., van Zuilen, A. D., Visseren, F. L. J., Wang, A. Y.-M., Wen, C.-P., Wheeler, D. C., Yatsuya, H., Yamagata, K., Yang, J. W., Young, A., Zhang, H., Zhang, L., Levey, A. S., & Gansevoort, R. T.
Affiliations
  • Writing Group for the CKD Prognosis Consortium
  • Peking University First Hospital (CN)
  • Tulane University (US)
  • Diabetes Centre and Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
  • Division of Nephrology, University of Alabama at Birmingham
  • Medical Research Council Population Health Research Unit, University of Oxford, Oxford, England
  • Programme in Health Services and Systems Research, Duke-NUS Medical School, Singapore
  • Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles
  • Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2023-10-03
Volume
330
Issue
13
Pages
1266
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2023.17002
PMC
PMC10548311
OpenAlex
W4387296715
Cited by
396
References
23
Citations by year
2026: 182 · 2025: 143 · 2024: 69 · 2023: 2
FWCI
76.85
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • JAMA (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
  • HAL (submittedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • Discovery Research Portal (University of Dundee) (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Figshare (submittedVersion)
Funders
  • Amgen
  • Eli Lilly and Company
  • AstraZeneca
  • GlaxoSmithKline
  • Sanofi
  • Brigham and Women's Hospital
  • Kaiser Permanente (UL1RR024131, P20 GM109036)
  • University of Pennsylvania (UL1-TR-000003, UL1 TR-000424)
  • Tufts Medical Center
  • MSD France
  • University of Washington
  • Tulane University (UL1 RR-024131, P20 GM109036)
  • Johns Hopkins University (UL1‐TR000424)
  • Deutsches Krebsforschungszentrum (M01 RR-16500)
  • University of Dundee
  • Wellcome Trust
  • University Hospitals of Leicester NHS Trust
  • Duke-NUS Medical School
  • Georgia Clinical and Translational Science Alliance (UL1RR029879, UL1TR000433)
  • Geisinger Commonwealth School of Medicine
  • York University
  • National Institute for Health and Care Research (ACF-2019-06-012)
  • British Heart Foundation
  • Kidney Research UK (JFDKcsf2/2017)
  • Diabetes UK
  • British Renal Society
  • Academy of Medical Sciences (SGL020\1076)
  • University of Leicester
  • Imperial College London
  • University of Oxford
  • Deutsche Forschungsgemeinschaft (431984000, 431 984 000-SFB 1453, SFB1453)
  • Institut National de la Santé et de la Recherche Médicale (U1018)
  • Rijksuniversiteit Groningen
  • University of New South Wales
  • Bundesministerium für Bildung und Forschung (01ER0820, 01ER0804, 01ER0818, 01ER0821, 431984000, 01ER0819, FKZ 01ER 0804)
  • Albert-Ludwigs-Universität Freiburg
  • Karolinska Institutet
  • Universitair Medisch Centrum Groningen
  • Högskolan Dalarna
  • Shahid Beheshti University of Medical Sciences
  • Universidad de la República Uruguay
  • Università degli Studi di Salerno
  • Otsuka Pharmaceutical
  • Boehringer Ingelheim France
  • National Institutes of Health (1s10od026880-01, UL1TR000433, UL1TR000424, UL1TR000003, 1s10od030463-01, UL1TR000439, U01-DK060990, N01-HC 25195, GM109036)
  • Centers for Disease Control and Prevention (75D301-19-Q-69877)
  • University of Illinois at Urbana-Champaign
  • School of Medicine, New York University
  • Duke Global Health Institute, Duke University
  • University of California, Los Angeles
  • Perelman School of Medicine, University of Pennsylvania (UL1TR000003)
  • University of California, San Francisco
  • Michigan Institute for Clinical and Health Research (UL1RR029879, UL1TR000433)
  • Johns Hopkins Bloomberg School of Public Health
  • Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University (UL1TR000439)
  • Medical Research Council (MR/R007764/1, MC_UU_00017/3)
  • National Health and Medical Research Council
  • Japan Society for the Promotion of Science (21K08271, 23K24607)
  • Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences
  • School of Medicine, Tokai University
  • National Heart, Lung, and Blood Institute (N01‐HC25195)
  • National Institute of General Medical Sciences (P20GM109036)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119199, NM R01DK119199, U01DK060990, N01-HC-25195, U01DK060984, U01DK060902, R01DK100446, U24DK060990, U01DK060980, U01DK061022, U01DK060963, U01DK061021, U01DK061028, P30DK079626)
  • National Center for Research Resources (UL1RR024131, M01RR016500, UL1RR029879)
  • National Center for Advancing Translational Sciences (M01RR16500)
  • NHLBI Division of Intramural Research
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
Keywords
estimated glomerular filtration rate, albuminuria, cystatin C, chronic kidney disease, renal failure, cardiovascular outcomes, all-cause mortality, cardiovascular mortality, acute kidney injury, hospitalization, coronary artery disease, stroke, heart failure, atrial fibrillation, peripheral arterial disease, albumin-creatinine ratio, individual patient data
MeSH terms
Adult, Aged, Albumins, Albuminuria, Atrial Fibrillation, Creatinine, Female, Glomerular Filtration Rate, Humans, Male, Middle Aged, Retrospective Studies, Comorbidity, Disease Progression, Internationality, Renal Insufficiency, Chronic, Cystatin C

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