Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes

Author:

,Appel Lawrence J1,Grams Morgan1,Woodward Mark1,Harris Katie1,Arima Hisatomi1,Chalmers John1,Yatsuya Hiroshi1,Tamakoshi Koji1,Li Yuanying1,Coresh Josef1,Sang Yingying1,Matsushita Kunihiro1,Polkinghorne Kevan1,Chadban Steve1,Levin Adeera1,Djurdjev Ognjenka1,Tang Mila1,Zhang Luxia1,Wang Fang1,Wang Jinwei1,Zhao Ming-Hui1,Schaeffner Elke1,Ebert Natalie1,Mielke Nina1,Tonelli Marcello1,Lloyd Anita1,Sacks Frank1,Shlipak Michael G1,Bansal Nisha1,Sarnak Mark1,Yamagishi Kazumasa1,Muraki Isao1,Shimizu Yuji1,Iso Hiroyasu1,Fukagawa Masafumi1,Maruyama Shoichi1,Hamano Takayuki1,Fujii Naohiko1,Imaizumi Takahiro1,Alencar De Pinho Natalia1,Metzger Marie1,Stengel Bénédicte1,Hamroun Aghilès1,Massy Ziad1,Jafar Tazeen H1,Jehan Imtiaz1,Hatcher Juanita1,Chaturvedi Nish1,Poulter Neil1,Wheeler David C1,Landray Martin1,Anderson Amanda1,Chen Jing1,Lash James1,Taliercio Jon1,Yang Peter (Wei)1,Tuttle Katherine1,Alicic Radica1,Nicholas Susanne1,Shen Jenny1,Schöttker Ben1,Stocker Hannah1,Rothenbacher Dietrich1,Brenner Hermann1,Levy Daniel1,Hwang Shih-Jen1,Schneider Markus P1,Köttgen Anna1,Meiselbach Heike1,Eckardt Kai-Uwe1,Chang Alexander R1,Green Jamie A1,Kirchner H Lester1,Singh Gurmukteshwar1,Sawhney Simon1,Black Corri1,Wilde Katie1,Marks Angharad1,Bell Samira1,Siddiqui Moneeza1,Palmer Colin1,Pearson Ewan1,Miyazaki Mariko1,Nakayama Masaaki1,Yamamoto Tae1,Yamada Gen1,Ito Sadayoshi1,Cirillo Massimo1,Wang Angela Yee-Moon1,Wu Henry Hon-Lin1,Cheung Hoi Ching1,Ngai Victoria1,Tak Tang Ka1,Garg Amit X1,McArthur Eric1,Young Ann1,Jha Vivekanand1,Yadav Ashok Kumar1,Kumar Vivek1,Carson April P1,Young Bessie A1,Diamantidis Clarissa1,Min Yuan-I1,Purnell Tanjala S1,Ishikawa Shizukiyo1,Mieno Makiko1,Yamagata Kunihiro1,Iseki Kunitoshi1,Asahi Koichi1,Konta Tsuneo1,Lee Brian J1,Brunskill Nigel J1,Gray Laura1,Major Rupert1,Medcalf James1,Chodick Gabriel1,Melzer Cohen Cheli1,Wetzels Jack FM1,Blankestijn Peter J1,van Zuilen Arjan D1,Inker Lesley A1,Levey Andrew S1,Ix Joachim1,de Boer Ian1,Katz Ronit1,Kronenberg Florian1,Kollerits Barbara1,Ritz Eberhard1,Nitsch Dorothea1,Nadkarni Girish N1,Chan Lili1,Bottinger Erwin P1,Oh Wonsuk1,Liu Zhihong1,Zhang Haitao1,Zhang Lihua1,Valdivielso Jose M1,Bermudez-Lopez Marcelino1,Bozic Milica1,Caus Maite1,Diaz-Tocados Juan Miguel1,Stengel Benedicte1,Miura Katsuyuki1,Ueshima Hirotsugu1,Okayama Akira1,Kadota Aya1,Okamura Tomonori1,Sola Laura1,Ferreiro Alejandro1,Santiago Jose1,Rios Pablo1,Gadola  Liliana1,Silvariño Ricardo 1,Ohkubo Takayoshi1,Satoh Michihiro1,Metoki Hirohito1,Kikuya Masahiro1,Ciemins Elizabeth1,Mohl Jeff1,Nelson Robert G1,Hanson Robert L1,Looker Helen C1,Gansevoort Ron T1,Kieneker Lyanne M1,Bakker Stephan JL1,Moranne Olivier1,Couchoud Cecile1,Shepherd David1,Jassal Simerjot K1,Bergstrom Jaclyn1,Kovesdy Csaba P1,Sumida Keiichi1,Shrestha Prabin1,Gutierrez Orlando1,Cheung Katharine1,Muntner Paul1,Ilori Titi1,Pena Michelle1,Heerspink Hiddo JL1,Fu Edouard L1,Elinder Carl-Gustaf1,Barany Peter1,Carrero Juan J1,Evans Marie1,Sabanayagam Charumathi1,Cheng Ching-Yu1,Wong Tien Yin1,Yuen Crystal Chong Chun1,Herrington William1,Staplin Natalie1,Landray Martin J1,Baigent Colin1,Kalra Philip1,Chinnadurai Rajkumar1,Green Darren1,Sinha Smeeta1,Ritchie James1,Visseren Frank LJ1,Burger Pascal1,Emmelot Marielle1,van Welzen Berend1,John Oommen1,Gummidi Balaji1,Ghosh Arpita1,Naimark David1,Tangri Navdeep1,Wen Chi-Pang1,Tsai Min-Kuang1,Ueno Yoshiyuki1,Watanabe Masafumi1,Ichikawa Kazunobu1,Mirbolouk Mohammadhassan1,Azizi Fereidoun1,Hadaegh Farzad1,Hosseinpanah Farhad1,Shi Wen1,Arking Dan1,Ärnlöv Johan1,Larsson Anders1,Giedraitis Vilmantas1,Mark Patrick1,Traynor Jamie1,Sullivan Michael1,Lees Jennifer1,Yang Jae won1,Shin Jae il1,Lee Jun young1,Kim Jae seok1,Bilo Henk JG1,van Dijk Peter1,Edens Mireille1,Dille Joep1,Ballew Shoshana H1,Carrero Juan-Jesus1,Grams Morgan E1,Chen Jingsha1,Surapaneni Aditya1,Grams Morgan E.23,Coresh Josef3,Matsushita Kunihiro3,Ballew Shoshana H.3,Sang Yingying3,Surapaneni Aditya2,Alencar de Pinho Natalia4,Anderson Amanda5,Appel Lawrence J.3,Ärnlöv Johan67,Azizi Fereidoun8,Bansal Nisha9,Bell Samira10,Bilo Henk J. G.11,Brunskill Nigel J.12,Carrero Juan J.13,Chadban Steve14,Chalmers John151617,Chen Jing18,Ciemins Elizabeth19,Cirillo Massimo20,Ebert Natalie21,Evans Marie22,Ferreiro Alejandro23,Fu Edouard L.24,Fukagawa Masafumi25,Green Jamie A.2627,Gutierrez Orlando M.28,Herrington William G.2930,Hwang Shih-Jen3132,Inker Lesley A.33,Iseki Kunitoshi34,Jafar Tazeen3536,Jassal Simerjot K.3738,Jha Vivekanand3940,Kadota Aya41,Katz Ronit42,Köttgen Anna43,Konta Tsuneo44,Kronenberg Florian45,Lee Brian J.46,Lees Jennifer4748,Levin Adeera49,Looker Helen C.50,Major Rupert12,Melzer Cohen Cheli51,Mieno Makiko52,Miyazaki Mariko53,Moranne Olivier5455,Muraki Isao56,Naimark David57,Nitsch Dorothea58,Oh Wonsuk59,Pena Michelle60,Purnell Tanjala S.36162,Sabanayagam Charumathi6364,Satoh Michihiro65,Sawhney Simon6667,Schaeffner Elke21,Schöttker Ben68,Shen Jenny I.6970,Shlipak Michael G.7172,Sinha Smeeta73,Stengel Benedicte4,Sumida Keiichi74,Tonelli Marcello75,Valdivielso Jose M.76,van Zuilen Arjan D.77,Visseren Frank L. J.78,Wang Angela Yee-Moon79,Wen Chi-Pang80,Wheeler David C.81,Yatsuya Hiroshi82,Yamagata Kunihiro83,Yang Jae won84,Young Ann8586,Zhang Haitao87,Zhang Luxia88,Levey Andrew S.33,Gansevoort Ron T.89

Affiliation:

1. Writing Group for the CKD Prognosis Consortium

2. Division of Precision Medicine, Department of Medicine, Grossman School of Medicine, New York University, New York, New York

3. Department of Epidemiology and Welch Center for Prevention, Epidemiology, and Clinical Research, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland

4. Centre for Research in Epidemiology and Population Health, Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France

5. School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana

6. School of Health and Social Studies, Dalarna University, Falun, Sweden

7. Department of Neurobiology, Care Sciences, and Society, Family Medicine and Primary Care Unit, Karolinska Institutet, Huddinge, Sweden

8. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

9. Division of Nephrology, University of Washington, Seattle

10. Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, Scotland

11. Diabetes Centre and Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

12. Department of Cardiovascular Sciences, University of Leicester, and John Walls Renal Unit, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, England

13. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and Department of Clinical Science, Danderyd Hospital, Stockholm, Sweden

14. Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, Australia

15. George Institute for Global Health, University of New South Wales, Sydney, Australia

16. School of Public Health, Imperial College, London, England

17. Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India

18. Department of Medicine, School of Medicine, Tulane University, New Orleans, Louisiana

19. AMGA (American Medical Group Association), Alexandria, Virginia

20. Department Scuola Medica Salernitana, University of Salerno, Fisciano, Italy

21. Institute of Public Health, Charité Universitätsmedizin Berlin, Berlin, Germany

22. Department of Renal Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

23. Departamento de Nefrología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay

24. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts

25. Division of Nephrology, Endocrinology, and Metabolism, School of Medicine, Tokai University, Isehara, Japan

26. Department of Nephrology, Geisinger Commonwealth School of Medicine, Danville, Pennsylvania

27. Center for Kidney Health Research, Geisinger, Danville, Pennsylvania

28. Division of Nephrology, University of Alabama at Birmingham

29. Medical Research Council Population Health Research Unit, University of Oxford, Oxford, England

30. Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, England

31. Framingham Heart Study, Framingham, Massachusetts

32. Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland

33. Division of Nephrology, Tufts Medical Center, Boston, Massachusetts

34. Okinawa Heart and Renal Association, Okinawa, Japan

35. Programme in Health Services and Systems Research, Duke-NUS Medical School, Singapore

36. Duke Global Health Institute, Duke University, Durham, North Carolina

37. University of California–San Diego, La Jolla

38. San Diego VA Health Care System, San Diego, California

39. George Institute for Global Health India, New Delhi, India

40. George Institute for Global Health, School of Public Health, Imperial College, London, England

41. Department of Public Health, NCD Epidemiology Research Center, Shiga University of Medical Science, Otsu, Japan

42. Department of Obstetrics and Gynecology, University of Washington, Seattle

43. Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany

44. Department of Public Health and Hygiene, Yamagata University Faculty of Medicine, Yamagata, Japan

45. Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria

46. Kaiser Permanente, Hawaii Region, and Moanalua Medical Center, Honolulu, Hawaiʻi

47. School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland

48. Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, Scotland

49. Division of Nephrology, University of British Columbia, Vancouver, Canada

50. Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona

51. Maccabi Institute for Research and Innovation, Maccabi Healthcare Services, Tel-Aviv, Israel

52. Department of Medical Informatics, Center for Information, Jichi Medical University, Tochigi, Japan

53. Department of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

54. Service de Néphrologie Dialyse Aphérèse, Nîmes Hôpital Universitaire, Nîmes, France

55. IDESP, UMR-INSERM, Universite de Montpellier, Montpellier, France

56. Public Health, Osaka University Graduate School of Medicine, Suita, Japan

57. Department of Medicine and Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada

58. London School of Hygiene and Tropical Medicine, London, England

59. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York

60. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

61. Division of Transplantation, Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, Maryland

62. Center for Health Equity, Johns Hopkins University, Baltimore, Maryland

63. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore

64. Ophthalmology and Visual Sciences Academic Clinical Programme, Duke-NUS Medical School, Singapore

65. Division of Public Health, Hygiene, and Epidemiology, Tohoku Medical and Pharmaceutical University, Sendai, Japan

66. Aberdeen Centre for Health Data Science, School of Medicine, Medical Sciences, and Nutrition, University of Aberdeen, Aberdeen, Scotland

67. NHS Grampian, Aberdeen, Scotland

68. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany

69. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles

70. Lundquist Institute, Harbor-UCLA Medical Center, Torrance, California

71. Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco

72. General Internal Medicine Division, Medical Service, San Francisco Veterans Affairs Health Care System, San Francisco, California

73. Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, England

74. Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis

75. Department of Medicine, University of Calgary, Calgary, Alberta, Canada

76. Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida, IRBLleida and University of Lleida, Lleida, Spain

77. Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands

78. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands

79. Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China

80. Institute of Population Health Science, National Health Research Institutes, Zhunan, Taiwan/China Medical University Hospital, Taichung, Taiwan

81. Department of Renal Medicine, University College London, London, England

82. Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan

83. Department of Nephrology, University of Tsukuba, Tsukuba, Japan

84. Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, South Korea

85. Division of Nephrology, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada

86. ICES Western, London, Ontario, Canada

87. National Clinical Research Center of Kidney Diseases, Jinling Hospital, Medical School of Nanjing University, Nanjing, China

88. Peking University First Hospital, Beijing, China

89. Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

Abstract

ImportanceChronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.ObjectiveTo 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 ParticipantsIndividual-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.ExposuresThe 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 MeasuresThe 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.ResultsWithin 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 RelevanceIn 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.

Publisher

American Medical Association (AMA)

Subject

General Medicine

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