Claudia S Lennartz1, John William Pickering2, Sarah Seiler-Mußler1, Lucie Bauer1, Kathrin Untersteller1, Insa E Emrich1, Adam M Zawada1, Jörg Radermacher3, Navdeep Tangri4, Danilo Fliser1, Gunnar H Heine5. 1. Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany; 2. Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand; Emergency Department, Christchurch Hospital, Christchurch, New Zealand; 3. Department of Nephrology and Hypertension, Johannes Wesling Klinikum, Minden, Germany; and. 4. Department of Medicine and Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada. 5. Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany; gunnar.heine@uks.eu.
Abstract
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 4.4±1.6 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 AND OBJECTIVES: Progression of CKD toward ESRD is heterogeneous. The Kidney Failure Risk Equation (KFRE) was developed to identify CKDpatients 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 4.4±1.6 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 CKDpatients. 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 CKDpatients did not improve risk prediction for progression to ESRD beyond a validated equation.
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