title: Proteinuria and stroke: a meta-analysis of cohort studies.
abstract: BACKGROUND
  The associations between decreased kidney function and cardiovascular disease recently have been established. However, there is uncertainty about the consistency between the independent associations of proteinuria as a risk factor across all cardiovascular end points. We undertook a meta-analysis of published cohort studies to provide a reliable estimate of the strength of association between proteinuria and risk of stroke.
  
  
  METHODS
  Meta-analysis of observational cohort studies.
  
  
  METHODS
  General population of participants with diabetes. Studies were excluded if participants had known glomerular disease or had undergone dialysis or transplantation.
  
  
  METHODS
  MEDLINE, EMBASE, and CINAHL databases were searched for studies that reported age- or multivariate-adjusted risk ratio with some estimate of the variance of the association between proteinuria and risk of stroke, without language restriction.
  
  
  METHODS
  Proteinuria or albuminuria.
  
  
  RESULTS
  Fatal or nonfatal stroke.
  
  
  RESULTS
  Data from 10 published studies involving 140,231 participants and 3,266 strokes were eligible for inclusion. Participants with proteinuria had a 71% greater risk of stroke compared with those without proteinuria (95% confidence interval, 1.39 to 2.10). There was evidence of significant quantitative heterogeneity in the magnitude of the association across studies (I(2) = 60%; P for heterogeneity = 0.008), which was partially explained by differences in methods for measuring proteinuria. The risk of stroke remained significant after adjustment for other vascular risk factors.
  
  
  CONCLUSIONS
  Because individual patient data were unavailable, we were unable to fully examine the impact of adjustment for known cardiovascular risk factors on the strength of the association between proteinuria and stroke risk. It is possible that the pooled estimate was affected by regression dilution bias.
  
  
  CONCLUSIONS
  These findings support the independent relationship between proteinuria and stroke. Additional studies are warranted to determine whether interventions to reduce proteinuria are effective at reducing rates of stroke.
authors.affiliation: The George Institute for International Health, The University of Sydney, Sydney, Australia.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.forename: Christine
authors.initials: C
authors.lastname: Verdon
authors.forename: Federica
authors.initials: F
authors.lastname: Barzi
authors.forename: Alan
authors.initials: A
authors.lastname: Cass
authors.forename: Martin
authors.initials: M
authors.lastname: Gallagher
authors.forename: Meg
authors.initials: M
authors.lastname: Jardine
authors.forename: Craig
authors.initials: C
authors.lastname: Anderson
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.forename: Rachel
authors.initials: R
authors.lastname: Huxley
mesh_terms: D015331:Cohort Studies; D006801:Humans; D011507:Proteinuria / Q000150:complications*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology*