American Journal of Kidney Diseases
Volume 53, Issue 3 , Pages 417-425, March 2009

Proteinuria and Stroke: A Meta-analysis of Cohort Studies

  • Toshiharu Ninomiya, MD, PhD

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • ,
  • Vlado Perkovic, MD, PhD

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • Corresponding Author InformationAddress correspondence to Vlado Perkovic, MD, PhD, The George Institute for International Health, The University of Sydney, Level 10, King George V Bldg, Royal Prince Alfred Hospital, Camperdown, Sydney NSW 2050, Australia
    • ,
  • Christine Verdon, MSc(A)

      Affiliations

    • School of Public Health, The University of Sydney, Sydney, Australia
    • ,
  • Federica Barzi, PhD

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • ,
  • Alan Cass, MD, PhD

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • ,
  • Martin Gallagher, MD, MPH

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • ,
  • Meg Jardine, MD

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • ,
  • Craig Anderson, MD, PhD

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • ,
  • John Chalmers, MD, PhD

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia
    • ,
  • Jonathan C. Craig, MD, PhD

      Affiliations

    • School of Public Health, The University of Sydney, Sydney, Australia
    • ,
  • Rachel Huxley, DPhil

      Affiliations

    • The George Institute for International Health, The University of Sydney, Sydney, Australia

Received 30 April 2008; accepted 29 August 2008. published online 15 December 2008.

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.

Study Design

Meta-analysis of observational cohort studies.

Setting & Population

General population of participants with diabetes. Studies were excluded if participants had known glomerular disease or had undergone dialysis or transplantation.

Selection Criteria for Studies

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.

Factor

Proteinuria or albuminuria.

Outcomes

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 (I2 = 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.

Limitations

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.

Index Words: Stroke, epidemiology, risk factors, proteinuria, meta-analysis

 

 Originally published online as doi:10.1053/j.ajkd.2008.08.032 on December 15, 2008.

PII: S0272-6386(08)01430-3

doi:10.1053/j.ajkd.2008.08.032

American Journal of Kidney Diseases
Volume 53, Issue 3 , Pages 417-425, March 2009

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