Background and objectives Progression of CKD toward ESRD is heterogeneous. The Kidney Failure Risk Equation (KFRE) was developed to identify CKD patients at high risk of ESRD. We aimed to externally validate KFRE and to test whether the addition of predefined Duplex ultrasound markers -renal resistive index (RRI) or difference of resistive indices in spleen and kidney (DI-RISK) -improved ESRD prediction.Design, setting, participants, & measurements The prospective Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Fourth Homburg evaluation (CARE FOR HOMe) study recruits CKD stage G2-G4 patients referred to a tertiary referral center for nephrologic care. Four hundred three CARE FOR HOMe participants enrolled between 2008 and 2012 had available RRI measurements at study inclusion; they were subsequently followed for a mean of 4.461.6 years. This subcohort was used to validate KFRE and to assess the added value of the ultrasound markers (new models KFRE+RRI and KFRE+DI-RISK). Model performance was assessed by log-likelihood ratio test, c-statistic, integrated discrimination improvement metrics (for study participants without subsequent ESRD [IDI No ESRD ] and for patients with ESRD [IDI ESRD ]), and calibration plots. If either new model improved on KFRE, we determined to validate it in an independent cohort of 162 CKD patients.Results KFRE predicted ESRD in CARE FOR HOMe participants with a c-statistic of 0.91 (95% confidence interval, 0.83 to 0.99). Adding RRI improved the KFRE model (P,0.001), and the KFRE+RRI model was well calibrated; however, the c-statistic (0.91 [0.83-1.00]) was similar, and overall sensitivity (IDI No ESRD =0.05 [0.00-0.10]) or overall specificity (IDI ESRD =0.00 [0.00-0.01]) did not improve. Adding DI-RISK did not improve the KRFE model. In the external validation cohort, we confirmed that the KFRE+RRI model did not outperform KFRE.Conclusions Routine Duplex examinations among CKD patients did not improve risk prediction for progression to ESRD beyond a validated equation.

Background: Kidney Disease Improving Global Outcomes (KDIGO) guidelines encourage clinicians to estimate 24-hour albuminuria as albumin to creatinine ratio (ACR) from spot urine samples. However, ACR underestimates 24-hour albumin excretion in muscular individuals. Equations that adjust ACR for surrogates of muscle mass to yield an estimated albumin excretion rate (eAER) were developed. We hypothesised that eAER is a better predictor of cardiovascular and renal outcomes than ACR. Methods: We determined ACR and eAER among 443 patients with chronic kidney disease G2-G4 recruited into the CARE FOR HOMe study. Patients were classified into KDIGO albuminuria categories, and followed for cardiovascular and renal events. The primary analysis was the net reclassification improvement (NRI) for those with and without events within 3 years of follow-up. Results: Eighty five patients experienced cardiovascular events during 3 years of follow-up, 13 of whom were reclassified to a more advanced albuminuria category, and 1 patient to a less advanced category by eAER compared to ACR (NRI_event: 14.1% (95% CI 5.8-22.4)). Among 358 patients without a cardiovascular event, 17 patients were reclassified to a more advanced albuminuria category, and 2 patients to a less advanced category by eAER (NRI_{no event}: -4.2%, 95% CI -8.5 to -1.8). Sixty patients went through renal events, and 383 patients had event-free 3-year follow-up. NRI_event was 6.7% (95% CI -1.2 to 14.5), and NRI_{no event} was -6.0% (95% CI -10.6 to 3.4) for renal events. Conclusion: Compared to ACR albuminuria categories, eAER categories are better associated with future cardiovascular events, but not with renal events.

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