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Research

Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f324 (Published 29 January 2013) Cite this as: BMJ 2013;346:f324
  1. Dorothea Nitsch, clinical senior lecturer1,
  2. Morgan Grams, assistant professor2,
  3. Yingying Sang, biostatistician3,
  4. Corri Black, senior clinical lecturer4,
  5. Massimo Cirillo, associate professor5,
  6. Ognjenka Djurdjev, corporate director6,
  7. Kunitoshi Iseki, director8,
  8. Simerjot K Jassal, clinical professor9,
  9. Heejin Kimm, assistant professor10,
  10. Florian Kronenberg, professor11,
  11. Cecilia M Øien, associate professor12,
  12. Andrew S Levey, professor13,
  13. Adeera Levin, professor7,
  14. Mark Woodward, professor14,
  15. Brenda R Hemmelgarn, associate professor15
  16. for the Chronic Kidney Disease Prognosis Consortium
  1. 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
  2. 2Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore MD, USA
  3. 3Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA
  4. 4Chronic Disease Research Group, Medical School, Aberdeen, UK
  5. 5Department of Medicine (Nephrology), University of Salerno, Baronissi (SA), Italy
  6. 6Provincial Health Services Authority, Vancouver BC, Canada
  7. 7Division of Nephrology UBC, St.Pauls Hospital, Vancouver BC, Canada
  8. 8Dialysis Unit, University Hospital of the Ryukyus, Okinawa, Japan
  9. 9VA San Diego Healthcare System, Division of GIM/G, San Diego CA, USA
  10. 10Institute for Health Promotion, Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea
  11. 11Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
  12. 12St Olavs Hospital, Department of Medicine, Section of Nephrology, Trondheim, Norway
  13. 13Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston MA, USA
  14. 14George Institute for Global Health, Camperdown NSW, Australia
  15. 15Division of Nephrology, Foothills Medical Centre, Calgary AB, Canada
  1. Correspondence to: A S Levey, Chronic Kidney Disease Prognosis Consortium. 615 N Wolfe Street, Baltimore, MD 21205, USA ckdpc{at}jhmi.edu
  • Accepted 28 December 2012

Abstract

Objective To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.

Design Random effects meta-analysis using pooled individual participant data.

Setting 46 cohorts from Europe, North and South America, Asia, and Australasia.

Participants 2 051 158 participants (54% women) from general population cohorts (n=1 861 052), high risk cohorts (n=151 494), and chronic kidney disease cohorts (n=38 612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m2) and urinary albumin-creatinine ratio (mg/g).

Results Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (Pinteraction<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (Pinteraction<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.

Conclusions Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

Footnotes

  • The Chronic Kidney Disease Prognosis Consortium (CKD-PC) investigators and collaborators: AASK—Jackson Wright, Lawrence Appel, Tom Greene, Brad C Astor; ADVANCE—John Chalmers, Stephen MacMahon, Mark Woodward, Hisatomi Arima; Aichi—Hiroshi Yatsuya, Kentaro Yamashita, Hideaki Toyoshima, Koji Tamakoshi; AKDN—Marcello Tonelli, Brenda Hemmelgarn, Aminu Bello, Matt James; ARIC—Josef Coresh, Brad C Astor, Kunihiro Matsushita, Yingying Sang; AusDiab—Robert C Atkins, Kevan R Polkinghorne, Steven Chadban; Beaver Dam CKD—Anoop Shankar, Ronald Klein, Barbara EK Klein, Kristine E Lee; Beijing Cohort—Haiyan Wang, Fang Wang, Luxia Zhang, Li Zuo; British Columbia CKD—Adeera Levin, Ognjenka Djurdjev; CARE—Marcello Tonelli, Frank M Sacks, Gary C Curhan; CHS—Michael Shlipak, Carmen Peralta, Ronit Katz, Linda Fried; CIRCS—Hiroyasu Iso, Akihiko Kitamura, Tetsuya Ohira, Kazumasa Yamagishi; COBRA—Tazeen H Jafar, Muhammad Islam, Juanita Hatcher, Neil Poulter, Nish Chaturvedi; CRIB—Martin J Landray, Jonathan Emberson, John N Townend, David C Wheeler; ESTHER—Dietrich Rothenbacher, Hermann Brenner, Heiko Müller, Ben Schöttker; Framingham—Caroline S Fox, Shih-Jen Hwang, James B Meigs; Geisinger—Robert M Perkins; GLOMMS-1 Study—Nick Fluck, Laura E Clark, Gordon J Prescott, Angharad Marks, Corri Black; Gubbio—Massimo Cirillo; HUNT—Stein Hallan, Knut Aasarød, Cecilia M Øien, Marie Radtke; IPHS—Fujiko Irie, Hiroyasu Iso, Toshimi Sairenchi, Kazumasa Yamagishi; Kaiser Permanente NW—David H Smith, Jessica W Weiss, Eric S Johnson, Micah L Thorp; KEEP—Allan J Collins, Joseph A Vassalotti, Suying Li, Shu-Cheng Chen; KP Hawaii—Brian J Lee; MASTERPLAN—Jack F Wetzels, Peter J Blankestijn, Arjan D van Zuilen; MDRD—Mark Sarnak, Andrew S Levey, Vandana Menon; MESA—Michael Shlipak, Mark Sarnak, Carmen Peralta, Ronit Katz, Holly J Kramer, Ian H de Boer; MMKD—Florian Kronenberg, Barbara Kollerits, Eberhard Ritz; MRC Older People—Paul Roderick, Dorothea Nitsch, Astrid Fletcher, Christopher Bulpitt; MRFIT—Areef Ishani, James D Neaton; NephroTest—Marc Froissart, Benedicte Stengel, Marie Metzger, Jean-Philippe Haymann, Pascal Houillier, Martin Flamant; NHANES III—Brad C Astor, Josef Coresh, Kunihiro Matsushita; Ohasama—Takayoshi Ohkubo, Hirohito Metoki, Masaaki Nakayama, Masahiro Kikuya, Yutaka Imai; Okinawa 83/93—Kunitoshi Iseki; Pima Indian—Robert G Nelson, William C Knowler; PREVEND—Ron T Gansevoort, Paul E de Jong, Bakhtawar K Mahmoodi, Hans Hillege; Rancho Bernardo—Simerjot Kaur Jassal, Elizabeth Barrett-Connor, Jaclyn Bergstrom; RENAAL—Hiddo J Lambers Heerspink, Barry E Brenner, Dick de Zeeuw; Renal REGARDS—David G Warnock, Paul Muntner, Suzanne Judd, William McClellan; Severance—Sun Ha Jee, Heejin Kimm, Jaeseong Jo, Yejin Mok, Eunmi Choi; STENO—Peter Rossing, Hans-Henrik Parving; Sunnybrook—Navdeep Tangri, David Naimark; Taiwan GP—Chi-Pang Wen, Sung-Feng Wen, Chwen-Keng Tsao, Min-Kuang Tsai; ULSAM—Johan Ärnlöv, Lars Lannfelt, Anders Larsson; ZODIAC—Henk J Bilo, Hanneke Joosten, Nanno Kleefstra, Klaas H Groenier, Iefke Drion.

  • CKD-PC Steering Committee: Brad C Astor, Josef Coresh (chair), Ron T Gansevoort, Brenda R Hemmelgarn, Paul E de Jong, Andrew S Levey, Adeera Levin, Kunihiro Matsushita, Chi-Pang Wen, Mark Woodward.

  • CKD-PC Data Coordinating Center: Shoshana H Ballew (coordinator), Josef Coresh (principal investigator), Morgan Grams, Bakhtawar K Mahmoodi, Kunihiro Matsushita (director), Yingying Sang (lead programmer), Mark Woodward (senior statistician); Administrative support: Laura Camarata, Xuan Hui, Jennifer Seltzer, Heather Winegrad.

  • Contributors: All authors had full access to the analysis reports and tables and take responsibility for the integrity of the data and the accuracy of the data analysis. The CKD-PC contributed to all aspects of the study. Conception and design: DN, MG, BRH, ASL. Analysis and interpretation of the data: DN, MG, YS, MW, BRH. Critical revision of the article for important intellectual content, and final approval of the article: all authors. Statistical expertise: YS, MW. Obtaining of funding: J Coresh for the CKD Prognosis Consortium. Administrative, technical, or logistic support: MG, YS. Collection and assembly of data: YS.

  • Funding: The CKD-PC Data Coordinating Center is funded in part by a programme grant from the US National Kidney Foundation (NKF funding sources include Abbott) and an investigator initiated research grant from Amgen. Various sources have supported enrolment and data collection including laboratory measurements, and follow-up in the collaborating cohorts of the CKD-PC, including government agencies such as national institutes of health and medical research councils as well as foundations and industry sponsors listed in appendix 3 on bmj.com. The funders had no role in the design, analysis, interpretation of this study, and did not contribute to the writing of this report and the decision to submit the article for publication.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare financial support for the submitted work from the Scottish Chief Scientist office (CB) and CKD-PC/the National Kidney Foundation for data extraction (CB) and travel to research related meetings (ASL, DN); ASL has grants pending with the National Kidney Foundation, and NIH; FK received a research grant for the ARO consortium from Amgen and speaker honoraria from Genzyme; No other relationships or activities that could appear to have influenced the submitted work.

  • 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.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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