The Kidney Failure Risk Equation for prediction of end stage renal disease in UK primary care: An external validation and clinical impact projection cohort study

BackgroundThe Kidney Failure Risk Equation (KFRE) uses the 4 variables of age, sex, urine albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) in individuals with chronic kidney disease (CKD) to predict the risk of end stage renal disease (ESRD), i.e., the need for dialysis or a kidney transplant, within 2 and 5 years. Currently, national guideline writers in the UK and other countries are evaluating the role of the KFRE in renal referrals from primary care to secondary care, but the KFRE has had limited external validation in primary care. The study’s objectives were therefore to externally validate the KFRE’s prediction of ESRD events in primary care, perform model recalibration if necessary, and assess its projected impact on referral rates to secondary care renal services.Methods and findingsIndividuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values 2 more than 90 days apart and a urine ACR or protein-to-creatinine ratio measurement between 1 December 2004 and 1 November 2016 were included in the cohort. The cohort included 35,539 (5.6%) individuals (57.5% female, mean age 75.9 years, median CKD-EPI eGFR 51 ml/min/1.73 m2, median ACR 3.2 mg/mmol) from a total adult practice population of 630,504. Overall, 176 (0.50%) and 429 (1.21%) ESRD events occurred within 2 and 5 years, respectively. Median length of follow-up was 4.7 years (IQR 2.8 to 6.6). Model discrimination was excellent for both 2-year (C-statistic 0.932, 95% CI 0.909 to 0.954) and 5-year (C-statistic 0.924, 95% 0.909 to 0.938) ESRD prediction. The KFRE overpredicted risk in lower (ConclusionsIn this cohort, the recalibrated KFRE accurately predicted the risk of ESRD at 2 and 5 years in primary care. Its introduction into primary care for referrals to secondary care renal services may lead to a reduction in unnecessary referrals, and earlier referrals in those who go on to develop ESRD. However, further validation studies in more diverse cohorts of the clinical impact projections and suggested referral criteria are required before the latter can be clinically implemented.研究背景 肾功能衰竭风险评分模型（Kidney Failure Risk Equation, KFRE）以慢性肾脏病（chronic kidney disease, CKD）患者的年龄、性别、尿白蛋白肌酐比（urine albumin-to-creatinine ratio, ACR）及估算肾小球滤过率（estimated glomerular filtration rate, eGFR）这4项变量为基础，用于预测患者2年及5年内发生终末期肾脏病（end stage renal disease, ESRD）的风险，即需接受透析或肾移植的风险。目前，英国及其他国家的国内指南制定者正在评估KFRE在基层医疗向二级医疗转诊的肾病患者评估中的应用价值，但KFRE在基层医疗场景中的外部验证研究较为有限。因此本研究的目标为：在基层医疗队列中外部验证KFRE对ESRD事件的预测效能，必要时对模型进行重新校准，并评估其对二级肾脏医疗服务转诊率的潜在影响。 方法与结果 本队列纳入2004年12月1日至2016年11月1日期间，拥有至少2次间隔超过90天的慢性肾脏病流行病学合作组（Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI）估算eGFR检测结果，且同时拥有尿ACR或尿蛋白肌酐比检测结果的受试者。最终队列共纳入630504名成年诊疗人群中的35539名个体（占比5.6%），其中57.5%为女性，平均年龄75.9岁，中位CKD-EPI eGFR为51 ml/min/1.73 m²，中位尿ACR为3.2 mg/mmol。整体而言，分别有176例（0.50%）和429例（1.21%）受试者在2年及5年内发生了ESRD事件。中位随访时长为4.7年（四分位数间距2.8~6.6）。模型区分度表现优异：2年ESRD预测的C统计量为0.932（95%置信区间0.909~0.954），5年ESRD预测的C统计量为0.924（95%置信区间0.909~0.938）。KFRE对低风险人群的风险存在高估。结论：在本队列中，经重新校准后的KFRE可准确预测基层医疗人群2年及5年ESRD发病风险。将KFRE应用于基层医疗的肾病专科转诊评估，可减少不必要的转诊，并为最终发生ESRD的患者提供更早的转诊时机。然而，在将该模型应用于临床实践前，还需要在更多样化的队列中开展进一步验证研究，以评估其临床影响及推荐的转诊标准。