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

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 m(2) or <60 ml/min/1.73 m(2). 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 χ(2) statistics and I(2). 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 m(2) and seven assessed eGRF at both <60 ml/min/1.73 m(2) and 60-90 ml/min/1.73 m(2) 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 m(2) (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 m(2) (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 m(2) (P<0.001). In subgroup analyses among participants with an eGFR <60 ml/min/1.73 m(2), 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 m(2) v <40 ml/min/1.73 m(2) (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 m(2) 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.