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

Morgan E. Grams*, Josef Coresh, Kunihiro Matsushita, Shoshana H. Ballew, Yingying Sang, Aditya Surapaneni, Natalia Alencar De Pinho, Amanda Anderson, Lawrence J. Appel, Johan Arnlöv, Fereidoun Azizi, Nisha Bansal, Samira Bell, Henk J.G. Bilo, Nigel J. Brunskill, Juan J. Carrero, Steve Chadban, John Chalmers, Jing Chen, Elizabeth CieminsMassimo Cirillo, Natalie Ebert, Marie Evans, Alejandro Ferreiro, Edouard L. Fu, Masafumi Fukagawa, Jamie A. Green, Orlando M. Gutierrez, William G. Herrington, Shih Jen Hwang, Lesley A. Inker, Kunitoshi Iseki, Tazeen Jafar, Simerjot K. Jassal, Vivekanand Jha, Aya Kadota, Ronit Katz, Anna Köttgen, Tsuneo Konta, Florian Kronenberg, Brian J. Lee, Jennifer Lees, Adeera Levin, Helen C. Looker, Rupert Major, Cheli Melzer Cohen, Makiko Mieno, Mariko Miyazaki, Olivier Moranne, Isao Muraki, David Naimark, Dorothea Nitsch, Wonsuk Oh, Michelle Pena, Tanjala S. Purnell, Charumathi Sabanayagam, Michihiro Satoh, Simon Sawhney, Elke Schaeffner, Ben Schöttker, Jenny I. Shen, Michael G. Shlipak, Smeeta Sinha, Benedicte Stengel, Keiichi Sumida, Marcello Tonelli, Jose M. Valdivielso, Arjan D. Van Zuilen, Frank L.J. Visseren, Angela Yee Moon Wang, Chi Pang Wen, David C. Wheeler, Hiroshi Yatsuya, Kunihiro Yamagata, Jae Won Yang, Ann Young, Haitao Zhang, Luxia Zhang, Andrew S. Levey, Ron T. Gansevoort

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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 27503140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9067753 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 m2based 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.

Original languageEnglish
Pages (from-to)1266-1277
Number of pages12
JournalJAMA
Volume330
Issue number13
DOIs
Publication statusPublished - 3-Oct-2023

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