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Low glomerular filtration rate and risk of stroke: meta-analysis

BMJ 2010; 341 doi: (Published 30 September 2010) Cite this as: BMJ 2010;341:c4249
  1. Meng Lee, visiting scholar and instructor13,
  2. Jeffrey L Saver, director and professor1,
  3. Kuo-Hsuan Chang, instructor4,
  4. Hung-Wei Liao, director5,
  5. Shen-Chih Chang, epidemiologist6,
  6. Bruce Ovbiagele, associate professor12
  1. 1Stroke Center, 710 Westwood Plaza, University of California, Los Angeles, CA 90095, USA
  2. 2Department of Neurology, University of California, Los Angeles
  3. 3Department of Neurology, Chang Gung Memorial Hospital at Chiayi, Chang Gung University College of Medicine, Taiwan
  4. 4Department of Neurology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine
  5. 5Ching-Ten Clinic, Taiwan
  6. 6Department of Epidemiology, School of Public Health, University of California
  1. Correspondence to: B Ovbiagele Ovibes{at}
  • Accepted 25 June 2010


Objective To qualitatively and quantitatively investigate the link between a low estimated glomerular filtration rate (eGFR) at baseline and risk of future stroke.

Design Systematic review and meta-analysis of prospective studies.

Data sources PubMed (1966-October 2009) and Embase (1947-October 2009).

Selection criteria Inclusion criteria were studies that prospectively collected data within cohort studies or clinical trials, estimated glomerular filtration rate at baseline using the modification of diet in renal disease or Cockcroft-Gault equations, assessed incident stroke, had a follow-up of at least one year, and reported quantitative estimates of multivariate adjusted relative risk and 95% confidence interval for stroke associated with an eGFR of 60-90 ml/min/1.73 m2 or <60 ml/min/1.73 m2.

Data abstraction Two investigators independently abstracted data from eligible studies. Estimates were combined using a random effects model. Heterogeneity was assessed by P value of χ2 statistics and I2. Publication bias was assessed by visual examination of funnel plots.

Results 21 articles derived from 33 prospective studies: 14 articles assessed eGFR <60 ml/min/1.73 m2 and seven assessed eGRF at both <60 ml/min/1.73 m2 and 60-90 ml/min/1.73 m2 for a total of 284 672 participants (follow-up 3.2-15 years) with 7863 stroke events. Incident stroke risk increased among participants with an eGFR <60 ml/min/1.73 m2 (relative risk 1.43, 95% confidence interval 1.31 to 1.57; P<0.001) but not among those with an eGFR of 60-90 ml/min/1.73 m2 (1.07, 0.98 to 1.17; P=0.15). Significant heterogeneity existed between estimates among patients with an eGFR <60 ml/min/1.73 m2 (P<0.001). In subgroup analyses among participants with an eGFR <60 ml/min/1.73 m2, heterogeneity was significant in Asians compared with non-Asians (1.96, 1.73 to 2.23 v 1.25, 1.16 to 1.35; P<0.001), and those with an eGFR of 40-60 ml/min/1.73 m2 v <40 ml/min/1.73 m2 (1.28, 1.04 to 1.56 v 1.77, 1.32 to 2.38; P<0.01).

Conclusions A baseline eGFR <60 ml/min/1.73 m2 was independently related to incident stroke across a variety of participants and study designs. Prompt and appropriate implementation of established strategies for reduction of vascular risk in people with know renal insufficiency may prevent future strokes.


  • We thank Yueh Lee for retrieving the papers.

  • Contributors: ML and BO conceived the study. ML, S-CC, and BO design the inclusion and exclusion criteria. ML, and K-HC participated in the study search and data collection and extraction. ML did the statistical analysis with guidance from JLS, S-CC, and BO. ML wrote the first draft of the report, and JLS, H-WL, and BO did the major revision and made comments. All other authors commented on the draft and approved the final version. ML and BO had full access to all the data and had the final decision to submit for publication. They are guarantors.

  • Funding: ML was supported by a grant from Chang Gung Memorial Hospital, Taiwan (CMRPG 660311, Taiwan). JLS was supported by the specialised programme on translational research in acute stroke (SPOTRIAS) award (P50 NS044378) from the National Institutes of Health, and BO was supported by University of California, Los Angeles-Resource Centers for Minority Aging Research under National Institutes of Health/National Institutes on Aging grant No P30-AG021684. The sponsors played no role in the study design, data collection and analysis, or decision to submit the article for publication.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: no support from any company for the submitted work; no financial relationships with any companies that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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