title: External Validation of the Kidney Failure Risk Equation and Re-Calibration with Addition of Ultrasound Parameters.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany;
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Lennartz
authors.affiliation: Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand; Emergency Department, Christchurch Hospital, Christchurch, New Zealand;
authors.forename: John William
authors.initials: JW
authors.lastname: Pickering
authors.affiliation: Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany;
authors.forename: Sarah
authors.initials: S
authors.lastname: Seiler-Mußler
authors.affiliation: Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany;
authors.forename: Lucie
authors.initials: L
authors.lastname: Bauer
authors.affiliation: Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany;
authors.forename: Kathrin
authors.initials: K
authors.lastname: Untersteller
authors.affiliation: Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany;
authors.forename: Insa E
authors.initials: IE
authors.lastname: Emrich
authors.affiliation: Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany;
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.affiliation: Department of Nephrology and Hypertension, Johannes Wesling Klinikum, Minden, Germany; and.
authors.forename: Jörg
authors.initials: J
authors.lastname: Radermacher
authors.affiliation: Department of Medicine and Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Navdeep
authors.initials: N
authors.lastname: Tangri
authors.affiliation: Department of Nephrology and Hypertension, Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center and Saarland University Faculty of Medicine, Homburg, Germany;
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: 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.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
mesh_terms: D015415:Biomarkers; D002138:Calibration; D018450:Disease Progression; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology*; D008297:Male; D055641:Mathematical Concepts; D008875:Middle Aged; D015233:Models, Statistical; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000150:complications* / Q000175:diagnosis* / Q000000981:diagnostic imaging; D018570:Risk Assessment; D014463:Ultrasonography
chemical_list: D015415:Biomarkers
keywords: Doppler; calibration; chronic kidney failure; humans; prospective studies; renal insufficiency, chronic; survivors; tertiary care centers; ultrasonography