Validation of the kidney failure risk equation for end-stage kidney disease in Southeast Asia

Patients with chronic kidney disease (CKD) are at high risk of end-stage kidney disease (ESKD). The Kidney Failure Risk Equation (KFRE), which predicts ESKD risk among patients with CKD, has not been validated in primary care clinics in Southeast Asia (SEA). Therefore, we aimed to (1) evaluate the performance of existing KFRE equations, (2) recalibrate KFRE for better predictive precision, and (3) identify optimally feasible KFRE thresholds for nephrologist referral and dialysis planning in SEA. All patients with CKD visiting nine primary care clinics from 2010 to 2013 in Singapore were included and applied 4-variable KFRE equations incorporating age, sex, estimated glomerular filtration rate (eGFR), and albumin-to-creatinine ratio (ACR). ESKD onset within two and five years were acquired via linkage to the Singapore Renal Registry. A weighted Brier score (the squared difference between observed vs predicted ESKD risks), bias (the median difference between observed vs predicted ESKD risks) and precision (the interquartile range of the bias) were used to select the best-calibrated KFRE equation. The recalibrated KFRE (named Recalibrated Pooled KFRE SEA) performed better than existing and other recalibrated KFRE equations in terms of having a smaller Brier score (square root: 2.8% vs. 4.0-9.3% at 5 years; 2.0% vs. 6.1-9.1% at 2 years), less bias (2.5% vs. 3.3-5.2% at 5 years; 1.8% vs. 3.2-3.6% at 2 years), and improved precision (0.5% vs. 1.7-5.2% at 5 years; 0.5% vs. 3.8-4.2% at 2 years). Area under ROC curve for the Recalibrated Pooled KFRE SEA equations were 0.94 (95% confidence interval [CI]: 0.93 to 0.95) at 5 years and 0.96 (95% CI: 0.95 to 0.97) at 2 years. The optimally feasible KFRE thresholds were > 10-16% for 5-year nephrologist referral and > 45% for 2-year dialysis planning. Using the Recalibrated Pooled KFRE SEA, an estimated 82 and 89% ESKD events were included among 10% of subjects at highest estimated risk of ESKD at 5-year and 2-year, respectively. The Recalibrated Pooled KFRE SEA performs better than existing KFREs and warrants implementation in primary care settings in SEA.