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 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 m²v <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.