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

BackgroundLower 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 FindingsStudies 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.
ConclusionsLower 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.

**研究背景**：估算肾小球滤过率（estimated glomerular filtration rate, eGFR）偏低与主要血管事件（major vascular events, MVEs）及死亡风险升高相关，但不同研究采用的方法学差异使得跨研究对比存在难度。本研究采用一种新型方法对已发表的研究结果进行汇总分析。

**研究方法与结果**：本研究通过PubMed检索评估基线eGFR与后续主要血管事件或全因死亡率相关性的研究。纳入标准为：研究纳入至少500名受试者、计划至少1年的随访周期、报告了校正年龄与性别的相对风险，且提供了各分组的平均eGFR（或可用于估算平均eGFR的足够信息）。为消除不同研究间基础风险差异的影响，本研究将eGFR的研究内相对差异（而非绝对eGFR数值）与风险相关联。最终共有50项针对主要血管事件的研究（纳入200万名受试者）及67项针对全因死亡率的研究（纳入500万名受试者）符合纳入标准。分析显示，eGFR偏低与主要血管事件及死亡风险呈负相关。在无既往血管疾病的人群研究中，eGFR每降低30%，平均而言主要血管事件风险升高29%（SE 0.2%），全因死亡风险升高31%（SE 0.2%）；在有既往血管疾病的人群研究中，上述风险分别升高26%（SE 1.0%）与23%（SE 0.2%）。尽管各项独立研究的结果间存在显著统计学异质性，但无论受试者是否有既往血管疾病史或研究设计类型如何，eGFR降低30%均始终与两类结局风险升高20%~30%相关。

**研究结论**：eGFR偏低始终与死亡及主要血管事件风险的轻度升高相关。若上述关联为因果关联且呈连续性，则70岁以上人群中约五分之一的血管事件可归因于肾功能受损。