title: Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.
abstract: BACKGROUND
  The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach.
  
  
  METHODS
  We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both.
  
  
  RESULTS
  The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105-0·0174] for ACR and 0·0065 [0·0042-0·0088] for eGFR) and heart failure (0·0196 [0·0108-0·0284] and 0·0109 [0·0059-0·0159]) than for coronary disease (0·0048 [0·0029-0·0067] and 0·0036 [0·0019-0·0054]) and stroke (0·0105 [0·0058-0·0151] and 0·0036 [0·0004-0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158-0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor.
  
  
  CONCLUSIONS
  Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population.
  
  
  BACKGROUND
  US National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases.
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Electronic address: ckdpc@jhmi.edu.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Sang
authors.affiliation: The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study and the Center for Population Studies Framingham, MA, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fox
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: Duke-NUS Graduate Medical School, Singapore.
authors.forename: Tazeen
authors.initials: T
authors.lastname: Jafar
authors.affiliation: VA San Diego Healthcare and University of California San Diego, San Diego, CA, USA.
authors.forename: Simerjot K
authors.initials: SK
authors.lastname: Jassal
authors.affiliation: Diabetes Centre Zwolle, Isala hospital, Zwolle, Netherlands.
authors.forename: Gijs W D
authors.initials: GW
authors.lastname: Landman
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, AL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Muntner
authors.affiliation: Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Roderick
authors.affiliation: Department of Public Health, Dokkyo Medical University School of Medicine, Tochigi, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Sairenchi
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Schöttker
authors.affiliation: 8816 Manchester Rd, St Louis, MO 63144, USA.
authors.forename: Anoop
authors.initials: A
authors.lastname: Shankar
authors.affiliation: Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center, and Departments of Medicine, Epidemiology, and Biostatistics, University of California San Francisco, San Francisco, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Shlipak
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Townend
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: van Zuilen
authors.affiliation: Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yamagishi
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Ron
authors.initials: R
authors.lastname: Gansevoort
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Sarnak
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, AL, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ärnlöv
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000652:urine*; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000652:urine; D003327:Coronary Disease / Q000175:diagnosis / Q000453:epidemiology / Q000652:urine; D003404:Creatinine / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000175:diagnosis / Q000453:epidemiology / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000652:urine
chemical_list: D003404:Creatinine