School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom.
Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
JAMA Netw Open. 2022 Oct 3;5(10):e2238300. doi: 10.1001/jamanetworkopen.2022.38300.
IMPORTANCE: Kidney function is usually estimated from serum creatinine level, whereas an alternative glomerular filtration marker (cystatin C level) associates more closely with future risk of cardiovascular disease (CVD) and mortality. OBJECTIVES: To evaluate whether testing concordance between estimated glomerular filtration rates based on cystatin C (eGFRcys) and creatinine (eGFRcr) levels would improve risk stratification for future outcomes and whether estimations differ by age. DESIGN, SETTING, AND PARTICIPANTS: A prospective population-based cohort study (UK Biobank), with participants recruited between 2006-2010 with median follow-up of 11.5 (IQR, 10.8-12.2) years; data were collected until August 31, 2020. Participants had eGFRcr greater than or equal to 45 mL/min/1.73 m2, albuminuria (albumin <30 mg/g), and no preexisting CVD or kidney failure. EXPOSURES: Chronic kidney disease status was categorized by concordance between eGFRcr and eGFRcys across the threshold for hronic kidney disease (CKD) diagnosis (60 mL/min/1.73 m2). MAIN OUTCOMES AND MEASURES: Ten-year probabilities of CVD, mortality, and kidney failure were assessed according to CKD status. Multivariable-adjusted Cox proportional hazards models tested associations between CVD and mortality. Area under the receiving operating curve tested discrimination of eGFRcr and eGFRcys for CVD and mortality. The Net Reclassification Index assessed the usefulness of eGFRcr and eGFRcys for CVD risk stratification. Analyses were stratified by older (age 65-73 years) and younger (age <65 years) age. RESULTS: There were 428 402 participants: median age was 57 (IQR, 50-63) years and 237 173 (55.4%) were women. Among 76 629 older participants, there were 9335 deaths and 5205 CVD events. Among 351 773 younger participants, there were 14 776 deaths and 9328 CVD events. The 10-year probability of kidney failure was less than 0.1%. Regardless of the eGFRcr, the 10-year probabilities of CVD and mortality were low when eGFRcys was greater than or equal to 60 mL/min/1.73 m2; conversely, with eGFRcys less than 60 mL/min/1.73 m2, 10-year risks were nearly doubled in older adults and more than doubled in younger adults. Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr. Across a 7.5% 10-year risk threshold for CVD, eGFRcys improved case Net Reclassification Index by 0.7% (95% CI, 0.6%-0.8%) in older people and 0.7% (95% CI, 0.7%-0.8%) in younger people; eGFRcr did not add to CVD risk estimation. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that eGFRcr 45 to 59 mL/min/1.73 m2 includes a proportion of individuals at low risk and fails to capture a substantial proportion of individuals at high-risk for CVD and mortality. The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD.
重要性:肾脏功能通常通过血清肌酐水平来估计,而替代肾小球滤过标志物(胱抑素 C 水平)与未来心血管疾病(CVD)和死亡率的风险更密切相关。 目的:评估基于胱抑素 C(eGFRcys)和肌酐(eGFRcr)水平的估计肾小球滤过率(eGFR)的检测一致性是否会改善未来结局的风险分层,以及估计值是否因年龄而异。 设计、地点和参与者:一项前瞻性基于人群的队列研究(英国生物银行),参与者于 2006-2010 年招募,中位随访时间为 11.5(IQR,10.8-12.2)年;数据收集截至 2020 年 8 月 31 日。参与者的 eGFRcr 大于或等于 45 mL/min/1.73 m2,白蛋白尿(白蛋白<30 mg/g),且无预先存在的 CVD 或肾功能衰竭。 暴露:慢性肾脏病状态根据 eGFRcr 和 eGFRcys 在慢性肾脏病(CKD)诊断阈值(60 mL/min/1.73 m2)之间的一致性进行分类。 主要结果和测量:根据 CKD 状态评估 10 年 CVD、死亡率和肾功能衰竭的概率。多变量调整后的 Cox 比例风险模型测试了 CVD 和死亡率之间的关联。接受者操作特征曲线下面积测试了 eGFRcr 和 eGFRcys 对 CVD 和死亡率的区分度。净重新分类指数评估了 eGFRcr 和 eGFRcys 在 CVD 风险分层中的有用性。分析按年龄较大(65-73 岁)和年龄较小(<65 岁)分层。 结果:共有 428402 名参与者:中位年龄为 57(IQR,50-63)岁,237173 名(55.4%)为女性。在 76629 名年龄较大的参与者中,有 9335 人死亡,5205 人发生 CVD 事件。在 351773 名年龄较小的参与者中,有 14776 人死亡,9328 人发生 CVD 事件。肾功能衰竭的 10 年概率小于 0.1%。无论 eGFRcr 如何,当 eGFRcys 大于或等于 60 mL/min/1.73 m2 时,CVD 和死亡率的 10 年概率均较低;相反,当 eGFRcys 小于 60 mL/min/1.73 m2 时,老年人的 10 年风险几乎增加了一倍,年轻人的 10 年风险增加了一倍以上。与 eGFRcr 相比,eGFRcys 能更好地区分 CVD 和死亡率风险。在 CVD 10 年风险阈值为 7.5%的情况下,eGFRcys 在年龄较大的人群中使净重新分类指数提高了 0.7%(95%CI,0.6%-0.8%),在年龄较小的人群中提高了 0.7%(95%CI,0.7%-0.8%);eGFRcr 并未增加 CVD 风险估计。 结论和相关性:本研究结果表明,eGFRcr 为 45 至 59 mL/min/1.73 m2 包括了一部分低风险人群,且未能捕捉到相当一部分高 CVD 和死亡率风险人群。在轻度 CKD 中,eGFRcys 似乎对 CVD 和死亡率风险更敏感和特异。
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