Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes
Authors:   Writing Group for the CKD Prognosis Consortium, Appel Lawrence J , Grams Morgan , Woodward Mark , Harris Katie , Arima Hisatomi , Chalmers John , Yatsuya Hiroshi , Tamakoshi Koji , Li Yuanying , Coresh Josef , Sang Yingying , Matsushita Kunihiro , Polkinghorne Kevan , Chadban Steve , Levin Adeera , Djurdjev Ognjenka , Tang Mila , Zhang Luxia , Wang Fang , Wang Jinwei , Zhao Ming-Hui , Schaeffner Elke , Ebert Natalie , Mielke Nina , Tonelli Marcello , Lloyd Anita , Sacks Frank , Shlipak Michael G , Bansal Nisha , Sarnak Mark , Yamagishi Kazumasa , Muraki Isao , Shimizu Yuji , Iso Hiroyasu , Fukagawa Masafumi , Maruyama Shoichi , Hamano Takayuki , Fujii Naohiko , Imaizumi Takahiro , Alencar De Pinho Natalia , Metzger Marie , Stengel Bénédicte , Hamroun Aghilès , Massy Ziad , Jafar Tazeen H , Jehan Imtiaz , Hatcher Juanita , Chaturvedi Nish , Poulter Neil , Wheeler David C , Landray Martin , Anderson Amanda , Chen Jing , Lash James , Taliercio Jon , Yang Peter (Wei) , Tuttle Katherine , Alicic Radica , Nicholas Susanne , Shen Jenny , Schöttker Ben , Stocker Hannah , Rothenbacher Dietrich , Brenner Hermann , Levy Daniel , Hwang Shih-Jen , Schneider Markus P , Köttgen Anna , Meiselbach Heike , Eckardt Kai-Uwe , Chang Alexander R , Green Jamie A , Kirchner H Lester , Singh Gurmukteshwar , Sawhney Simon , Black Corri , Wilde Katie , Marks Angharad , Bell Samira , Siddiqui Moneeza , Palmer Colin , Pearson Ewan , Miyazaki Mariko , Nakayama Masaaki , Yamamoto Tae , Yamada Gen , Ito Sadayoshi , Cirillo Massimo , Wang Angela Yee-Moon , Wu Henry Hon-Lin , Cheung Hoi Ching , Ngai Victoria , Tak Tang Ka , Garg Amit X , McArthur Eric , Young Ann , Jha Vivekanand , Yadav Ashok Kumar , Kumar Vivek , Carson April P , Young Bessie A , Diamantidis Clarissa , Min Yuan-I , Purnell Tanjala S , Ishikawa Shizukiyo , Mieno Makiko , Yamagata Kunihiro , Iseki Kunitoshi , Asahi Koichi , Konta Tsuneo , Lee Brian J , Brunskill Nigel J , Gray Laura , Major Rupert , Medcalf James , Chodick Gabriel , Melzer Cohen Cheli , Wetzels Jack FM , Blankestijn Peter J , van Zuilen Arjan D , Inker Lesley A , Levey Andrew S , Ix Joachim , de Boer Ian , Katz Ronit , Kronenberg Florian , Kollerits Barbara , Ritz Eberhard , Nitsch Dorothea , Nadkarni Girish N , Chan Lili , Bottinger Erwin P , Oh Wonsuk , Liu Zhihong , Zhang Haitao , Zhang Lihua , Valdivielso Jose M , Bermudez-Lopez Marcelino , Bozic Milica , Caus Maite , Diaz-Tocados Juan Miguel , Stengel Benedicte , Miura Katsuyuki , Ueshima Hirotsugu , Okayama Akira , Kadota Aya , Okamura Tomonori , Sola Laura , Ferreiro Alejandro , Santiago Jose , Rios Pablo , Gadola  Liliana , Silvariño Ricardo  , Ohkubo Takayoshi , Satoh Michihiro , Metoki Hirohito , Kikuya Masahiro , Ciemins Elizabeth , Mohl Jeff , Nelson Robert G , Hanson Robert L , Looker Helen C , Gansevoort Ron T , Kieneker Lyanne M , Bakker Stephan JL , Moranne Olivier , Couchoud Cecile , Shepherd David , Jassal Simerjot K , Bergstrom Jaclyn , Kovesdy Csaba P , Sumida Keiichi , Shrestha Prabin , Gutierrez Orlando , Cheung Katharine , Muntner Paul , Ilori Titi , Pena Michelle , Heerspink Hiddo JL , Fu Edouard L , Elinder Carl-Gustaf , Barany Peter , Carrero Juan J , Evans Marie , Sabanayagam Charumathi , Cheng Ching-Yu , Wong Tien Yin , Yuen Crystal Chong Chun , Herrington William , Staplin Natalie , Landray Martin J , Baigent Colin , Kalra Philip , Chinnadurai Rajkumar , Green Darren , Sinha Smeeta , Ritchie James , Visseren Frank LJ , Burger Pascal , Emmelot Marielle , van Welzen Berend , John Oommen , Gummidi Balaji , Ghosh Arpita , Naimark David , Tangri Navdeep , Wen Chi-Pang , Tsai Min-Kuang , Ueno Yoshiyuki , Watanabe Masafumi , Ichikawa Kazunobu , Mirbolouk Mohammadhassan , Azizi Fereidoun , Hadaegh Farzad , Hosseinpanah Farhad , Shi Wen , Arking Dan , Ärnlöv Johan , Larsson Anders , Giedraitis Vilmantas , Mark Patrick , Traynor Jamie , Sullivan Michael , Lees Jennifer , Yang Jae won , Shin Jae il , Lee Jun young , Kim Jae seok , Bilo Henk JG , van Dijk Peter , Edens Mireille , Dille Joep , Ballew Shoshana H , Carrero Juan-Jesus , Grams Morgan E , Chen Jingsha , Surapaneni Aditya , Grams Morgan E. , Coresh Josef , Matsushita Kunihiro , Ballew Shoshana H. , Sang Yingying , Surapaneni Aditya , Alencar de Pinho Natalia , Anderson Amanda , Appel Lawrence J. , Ärnlöv Johan , Azizi Fereidoun , Bansal Nisha , Bell Samira , Bilo Henk J. G. , Brunskill Nigel J. , Carrero Juan J. , Chadban Steve , Chalmers John , Chen Jing , Ciemins Elizabeth , Cirillo Massimo , Ebert Natalie , Evans Marie , Ferreiro Alejandro , Fu Edouard L. , Fukagawa Masafumi , Green Jamie A. , Gutierrez Orlando M. , Herrington William G. , Hwang Shih-Jen , Inker Lesley A. , Iseki Kunitoshi , Jafar Tazeen , Jassal Simerjot K. , Jha Vivekanand , Kadota Aya , Katz Ronit , Köttgen Anna , Konta Tsuneo , Kronenberg Florian , Lee Brian J. , Lees Jennifer , Levin Adeera , Looker Helen C. , Major Rupert , Melzer Cohen Cheli , Mieno Makiko , Miyazaki Mariko , Moranne Olivier , Muraki Isao , Naimark David , Nitsch Dorothea , Oh Wonsuk , Pena Michelle , Purnell Tanjala S. , Sabanayagam Charumathi , Satoh Michihiro , Sawhney Simon , Schaeffner Elke , Schöttker Ben , Shen Jenny I. , Shlipak Michael G. , Sinha Smeeta , Stengel Benedicte , Sumida Keiichi , Tonelli Marcello , Valdivielso Jose M. , van Zuilen Arjan D. , Visseren Frank L. J. , Wang Angela Yee-Moon , Wen Chi-Pang , Wheeler David C. , Yatsuya Hiroshi , Yamagata Kunihiro , Yang Jae won , Young Ann , Zhang Haitao , Zhang Luxia , Levey Andrew S. , Gansevoort Ron T. 
Published: October 2023

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 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.