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

Background The 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 findings Individuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values < 60 ml/min/1.73 m2 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 (
In this cohort study, Rupert Major and colleagues evaluate the performance of the Kidney Failure Risk Equation in chronic kidney disease patients in primary care settings and project impact of a recalibrated equation on referral practices and patient outcomes.
Author summary Why was this study done? The Kidney Failure Risk Equation (KFRE) has been developed in multinational chronic kidney disease (CKD) cohorts to predict end stage renal disease (ESRD) events (the need for dialysis or a kidney transplant) over 2- and 5-year time periods. The performance of the KFRE has not been extensively tested in UK and European primary care CKD populations. The projected impact of the KFRE on referrals from primary to secondary care has not been studied, and it is unclear what criteria for referrals should be used. What did the researchers do and find? Our study suggests that the KFRE has largely accurate performance (discrimination) for predicting ESRD, but requires adjustment (recalibration) for a primary care setting. Compared to current referral criteria, using hybrid criteria of a ≥5% risk of ESRD over 5 years from the recalibrated KFRE and/or a urine albumin-to-creatinine ratio (ACR) of ≥70 mg/mmol would reduce the number of individuals eligible for referral without increasing the number who later develop ESRD and are not initially eligible for referral. What do these findings mean? The recalibrated KFRE can be used to predict the risk of ESRD over 2 and 5 years in primary care CKD. The KFRE, in conjunction with the ACR criterion, can be used to triage CKD referrals from primary to secondary care.