Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortiumBMJ 2019; 364 doi: https://doi.org/10.1136/bmj.k5301 (Published 10 January 2019) Cite this as: BMJ 2019;364:k5301
- Alex R Chang, assistant professor1,
- Morgan E Grams, associate professor2,
- Shoshana H Ballew, assistant scientist2,
- Henk Bilo, professor3,
- Adolfo Correa, professor4,
- Marie Evans, nephrologist5,
- Orlando M Gutierrez, professor6 7,
- Farhad Hosseinpanah, associate professor8,
- Kunitoshi Iseki, director9 10,
- Timothy Kenealy, associate professor11,
- Barbara Klein, professor12,
- Florian Kronenberg, professor13,
- Brian J Lee, nephrologist14,
- Yuanying Li, researcher15,
- Katsuyuki Miura, professor16,
- Sankar D Navaneethan, associate professor17,
- Paul J Roderick, professor18,
- Jose M Valdivielso, principal investigator19,
- Frank L J Visseren, professor20,
- Luxia Zhang, professor21,
- Ron T Gansevoort, professor22,
- Stein I Hallan, professor23 24,
- Andrew S Levey, professor25,
- Kunihiro Matsushita, associate professor2,
- Varda Shalev, director26,
- Mark Woodward, professor2 27 28
- on behalf of the CKD Prognosis Consortium (CKD-PC)
- 1Kidney Health Research Institute, and Department of Epidemiology and Health Services Research, Geisinger Health System, Danville, PA, USA
- 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- 3Diabetes Centre, Isala, and Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
- 4Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
- 5Division of Renal Medicine, CLINTEC, Karolinska Institutet, Stockholm, Sweden and Swedish Renal Registry, Jönköping, Sweden
- 6Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
- 7Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA
- 8Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- 9Dialysis Unit, University of the Ryukyus Hospital, Nishihara, Japan
- 10Yuuaikai Tomishiro Central Hospital, Tomigusuku, Okinawa, Japan
- 11Departments of Medicine and General Practice & Primary Health Care, School of Population Health, University of Auckland, Auckland, New Zealand
- 12Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
- 13Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
- 14Kaiser Permanente, Hawaii Region, Moanalua Medical Center, Honolulu, HI, USA
- 15Department of Public Health, Fujita Health University School of Medicine, Aichi, Japan
- 16Department of Public Health, Shiga University of Medical Science, Otsu, Japan
- 17Section of Nephrology, Baylor College of Medicine, Houston, TX, USA
- 18Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
- 19Vascular and Renal Translational Research Group, REDinREN del ISCIII, IRBLleida, Lleida, Spain
- 20Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, Netherlands
- 21Peking University Institute of Nephrology, Division of Nephrology, Peking University First Hospital, Beijing, China
- 22Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- 23Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science Technology, Trondheim, Norway
- 24Division of Nephrology, Department of Medicine, St Olav University Hospital, Trondheim, Norway
- 25Division of Nephrology at Tufts Medical Center, Boston, MA, USA
- 26Medical Division, Maccabi Healthcare Services, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- 27George Institute for Global Health, University of Oxford, Oxford, UK
- 28George Institute for Global Health, University of New South Wales, Sydney, Australia
- Correspondence to: M E Grams, Chronic Kidney Disease Prognosis Consortium Data Coordinating Center, 2024 E Monument Street, Baltimore, MD 21205, USA
- Accepted 7 November 2018
Objective To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.
Design Individual participant data meta-analysis.
Setting Cohorts from 40 countries with data collected between 1970 and 2017.
Participants Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607).
Main outcome measures GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality.
Results Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index.
Conclusions Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.
Contributors: MEG and KM had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. ARC, MW, MEG, KM, RTG, and ASL were responsible for the study concept and design. MEG, SHB, and KM with the CKD-PC investigators/collaborators listed below were involved in the acquisition of data. All the authors contributed to the analysis and interpretation of data and to the critical revision of the manuscript for important intellectual content. ARC, MW, and MEG drafted the manuscript. MEG guarantees the integrity of the work. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
CKD Prognosis Consortium (CKD-PC) investigators/collaborators (study acronyms/abbreviations are listed in eAppendix 2 in the supplementary materials): AASK: Brad Astor, Larry Appel, Tom Greene, Teresa Chen; ADVANCE: John Chalmers, Mark Woodward, Hisatomi Arima, Vlado Perkovic; Aichi: Hiroshi Yatsuya, Koji Tamakoshi, Yuanying Li, Yoshihisa Hirakawa; ARIC: Josef Coresh, Kunihiro Matsushita, Morgan Grams, Yingying Sang; AusDiab: Kevan Polkinghorne, Steven Chadban, Robert Atkins; BC CKD: Adeera Levin, Ognjenka Djurdjev; Beaver Dam CKD: Ron Klein, Barbara Klein, Kristine Lee; Beijing: Luxia Zhang, Lisheng Liu, Minghui Zhao, Fang Wang, Jinwei Wang; CanPREDDICT: Adeera Levin, Ognjenka Djurdjev, Mila Tang; CARE FOR HOMe: Gunnar Heine, Insa Emrich, Adam Zawada, Lucie Bauer; CCF: Joseph Nally, Sankar Navaneethan, Jesse Schold; ChinaNS: Luxia Zhang, Minghui Zhao, Fang Wang, Jinwei Wang; CHS: Michael Shlipak, Mark Sarnak, Ronit Katz, Jade Hiramoto; CIRCS: Hiroyasu Iso, Kazumasa Yamagishi, Mitsumasa Umesawa, Isao Muraki; CKD-JAC: Masafumi Fukagawa, Shoichi Maruyama, Takayuki Hamano, Takeshi Hasegawa, Naohiko Fujii; COBRA: Tazeen Jafar, Juanita Hatcher, Neil Poulter, Nish Chaturvedi; CRIB: David Wheeler, John Emberson, John Townend, Martin Landray; ESTHER: Hermann Brenner, Ben Schöttker, Kai-Uwe Saum, Dietrich Rothenbacher; Framingham: Caroline Fox, Shih-Jen Hwang; GCKD: Anna Köttgen, Florian Kronenberg, Markus P Schneider; Kai-Uwe Eckardt; Geisinger: Jamie Green, H Lester Kirchner, Alex R Chang; Gonryo: Sadayoshi Ito, Mariko Miyazaki, Masaaki Nakayama, Gen Yamada; Gubbio: Massimo Cirillo; HUNT: Stein Hallan, Solfrid Romundstad, Marius Øvrehus, Knut Asbjørn Langlo; IPHS: Fujiko Irie, Toshimi Sairenchi; JHS: Adolfo Correa, Casey M Rebholz, Bessie Young, L Ebony Boulware; JMS: Shizukiyo Ishikawa, Yuichiro Yano, Kazuhiko Kotani, Takeshi Nakamura; KHS: Sun Ha Jee, Heejin Kimm, Yejin Mok; KP Hawaii: Brian J Lee; Maccabi: Gabriel Chodick, Varda Shalev; MASTERPLAN: Jack F M Wetzels, Peter J Blankestijn, Arjan D van Zuilen, M Bots; MDRD: Mark Sarnak, Lesley Inker; MESA: Michael Shlipak, Mark Sarnak, Ronit Katz, Carmen Peralta; MMKD: Florian Kronenberg, Barbara Kollerits, Eberhard Ritz; MRC: Dorothea Nitsch, Paul Roderick, Astrid Fletcher; Mt Sinai BioMe: Erwin Bottinger, Girish N Nadkarni, Stephen B Ellis, Rajiv Nadukuru; Nefrona: Jose M Valdivielso, Elvira Fernandez, Angels Betriu, Marcelino Bermudez-Lopez; NephroTest: Benedicte Stengel, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann, Marc Froissart; NHANES: Yingying Sang; NIPPON DATA80: Hirotsugu Ueshima, Akira Okayama, Katsuyuki Miura, Sachiko Tanaka; NIPPON DATA90: Hirotsugu Ueshima, Tomonori Okamura, Katsuyuki Miura, Sachiko Tanaka; NZDCS: Timothy Kenealy, C Raina Elley, John F Collins, Paul L Drury; Ohasama: Takayoshi Ohkubo, Kei Asayama, Hirohito Metoki, Masahiro Kikuya, Masaaki Nakayama; Okinawa 83/93: Kunitoshi Iseki, Chiho Iseki; Pima: Robert G Nelson, William C Knowler; PREVEND: Ron T Gansevoort, Stephan J L Bakker, Hiddo J L Heerspink; PSP-CKD: Nigel Brunskill, Rupert Major, David Shepherd, James Medcalf; Rancho Bernardo: Simerjot K Jassal, Jaclyn Bergstrom, Joachim H Ix, Elizabeth Barrett-Connor; RCAV: Csaba Kovesdy, Kamyar Kalantar-Zadeh; Keiichi Sumida; REGARDS: Paul Muntner, David Warnock, Suzanne Judd, Bhupesh Panwar; RENAAL: Hiddo J L Heerspink, Dick de Zeeuw, Barry Brenner; RSIII: Sanaz Sedaghat, M Arfan Ikram, Ewout J Hoorn, Abbas Dehghan; SEED: Tien Yin Wong, Charumathi Sabanayagam, Ching-Yu Cheng, Riswana Banu Binte Mohamed Abdul Sokor; SMART: Frank L J Visseren; SRR-CKD: Marie Evans, Mårten Segelmark, Maria Stendahl, Staffan Schön; Sunnybrook: Navdeep Tangri, Maneesh Sud, David Naimark; Taiwan MJ: Chi-Pang Wen, Chwen-Keng Tsao, Min-Kugng Tsai, Chien-Hua Chen; Takahata: Tsuneo Konta, Atsushi Hirayama, Kazunobu Ichikawa; TLGS: Farhad Hosseinpanah, Farzad Hadaegh, Mohammadhassan Mirbolouk, Fereidoun Azizi; Tromso: Marit Dahl Solbu, Trond Geir Jenssen, Bjørn Odvar Eriksen, Anne Elise Eggen; ULSAM: Lars Lannfelt, Anders Larsson, Johan Ärnlöv; ZODIAC: Henk J G Bilo, Gijs W D Landman, Kornelis J J van Hateren, Nanne Kleefstra.
CKD-PC steering committee: Josef Coresh (chair), Ron T Gansevoort, Morgan E Grams, Stein Hallan, Csaba P Kovesdy, Andrew S Levey, Kunihiro Matsushita, Varda Shalev, Mark Woodward.
CKD-PC data coordinating centre: Shoshana H Ballew (assistant project director), Jingsha Chen (programmer), Josef Coresh (principal investigator), Morgan E Grams (director of nephrology initiatives), Lucia Kwak (programmer), Kunihiro Matsushita (director), Yingying Sang (lead programmer), Aditya Surapaneni (programmer), Mark Woodward (senior statistician).
Some of the data reported here were supplied by the United States Renal Data System (USRDS). The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; National Institutes of Health; or US Department of Health and Human Services.
Funding: The CKD-PC data coordinating centre is funded partly by a programme grant from the US National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; R01DK100446-01). Various sources have supported enrolment and data collection including laboratory measurements, and follow-up in the collaborating cohorts of the CKD-PC; these funding sources include government agencies such as national institutes of health and medical research councils as well as foundations and industry sponsors listed in eAppendix 3. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. ARC was supported by NIDDK (1K23DK106515-01).
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: part support from the US National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases for the submitted work; ARC was supported by the NIDDK; no other financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activites that could appear to have influenced the submitted work.
Ethical approval: Ethical approval was provided by the Johns Hopkins Bloomberg School of Public Health institutional review board.
Data sharing: CKD-PC has agreed with collaborating cohorts not to share data outside the consortium. Each participating cohort has its own policy for data sharing.
The lead author affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
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