Estimated Glomerular Filtration Rate and the Risk of Major Vascular Events and All-Cause Mortality: A Meta-Analysis

Background: Lower estimated glomerular filtration rate (eGFR) has been associated with an increased risk of major vascular events (MVEs) and death, but differences in methodology make between-study comparisons difficult. We used a novel method to summarise the published results. Methods and Findings: Studies assessing the relationship between baseline eGFR and subsequent MVEs or all cause mortality were identified using Pubmed. Those which involved at least 500 individuals, planned at least 1 year of follow-up, reported age and sex adjusted relative risks, and provided the mean eGFR in each category (or sufficient information to allow its estimation) were included. To take account of differences in underlying risk between studies, proportional within-study differences in eGFR (rather than absolute eGFR values) were related to risk. Fifty studies (2 million participants) assessing MVEs and 67 studies (5 million participants) assessing all cause mortality were eligible. There was an inverse relationship between lower eGFR and the risk of MVEs and of death. In studies among people without prior vascular disease, a 30% lower eGFR level was on average associated with a 29% (SE 0.2%) increase in the risk of a MVE and a 31% (SE 0.2%) increase in the risk of death from any cause. In studies among people with prior vascular disease, these estimates were 26% (SE 1.0%) and 23% (SE 0.2%) respectively. While there was substantial statistical heterogeneity between the results of individual studies, a 30% lower eGFR was consistently associated with a 20-30% higher risk of both outcomes, irrespective of prior history of vascular disease or study design. Conclusions: Lower eGFR was consistently associated with a moderate increase in the risk of death and MVEs. If these relationships are causal and continuous, then around one fifth of vascular events among those over 70 years might be attributable to renal impairment.