학술논문
Validation of the Klinrisk chronic kidney disease progression model in the FIDELITY population.
Document Type
Academic Journal
Author
Tangri N; Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.; Seven Oaks Hospital Chronic Disease Innovation Centre, Winnipeg, Manitoba, Canada.; Ferguson T; Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.; Seven Oaks Hospital Chronic Disease Innovation Centre, Winnipeg, Manitoba, Canada.; Leon SJ; Seven Oaks Hospital Chronic Disease Innovation Centre, Winnipeg, Manitoba, Canada.; University of Manitoba, Community Health Sciences, Winnipeg, Manitoba, Canada.; Anker SD; Department of Cardiology (CVK) of German Heart Center Charité; German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin, Berlin, Germany.; Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland.; Filippatos G; National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Attikon University Hospital, Athens, Greece.; Pitt B; Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.; Rossing P; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Ruilope LM; Cardiorenal Translational Laboratory and Hypertension Unit, Institute of Research imas12, Madrid, Spain.; CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain.; Faculty of Sport Sciences, European University of Madrid, Madrid, Spain.; Farjat AE; Research and Development, Clinical Data Sciences and Analytics, Bayer PLC, Reading, UK.; Farag YMK; US Medical Affairs, Bayer US LLC Pharmaceuticals, Whippany, NJ, USA.; Schloemer P; Statistics and Data Insights, Bayer AG, Berlin, Germany.; Lawatscheck R; Cardiology and Nephrology Clinical Development, Bayer AG, Berlin, Germany.; Rohwedder K; Cardio-Renal Medical Affairs Department, Bayer AG, Berlin, Germany.; Bakris GL; Department of Medicine, University of Chicago Medicine, Chicago, IL, USA.
Source
Publisher: Oxford University Press Country of Publication: England NLM ID: 101579321 Publication Model: eCollection Cited Medium: Print ISSN: 2048-8505 (Print) Linking ISSN: 20488505 NLM ISO Abbreviation: Clin Kidney J Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2048-8505
Abstract
Background: Chronic kidney disease (CKD) affects >800 million individuals worldwide and is often underrecognized. Early detection, identification and treatment can delay disease progression. Klinrisk is a proprietary CKD progression risk prediction model based on common laboratory data to predict CKD progression. We aimed to externally validate the Klinrisk model for prediction of CKD progression in FIDELITY (a prespecified pooled analysis of two finerenone phase III trials in patients with CKD and type 2 diabetes). In addition, we sought to identify evidence of an interaction between treatment and risk.
Methods: The validation cohort included all participants in FIDELITY up to 4 years. The primary and secondary composite outcomes included a ≥40% decrease in estimated glomerular filtration rate (eGFR) or kidney failure, and a ≥57% decrease in eGFR or kidney failure. Prediction discrimination was calculated using area under the receiver operating characteristic curve (AUC). Calibration plots were calculated by decile comparing observed with predicted risk.
Results: At time horizons of 2 and 4 years, 993 and 1795 patients experienced a primary outcome event, respectively. The model predicted the primary outcome accurately with an AUC of 0.81 for 2 years and 0.86 for 4 years. Calibration was appropriate at both 2 and 4 years, with Brier scores of 0.067 and 0.115, respectively. No evidence of interaction between treatment and risk was identified for the primary composite outcome ( P = .31).
Conclusions: Our findings demonstrate the accuracy and utility of a laboratory-based prediction model for early identification of patients at the highest risk of CKD progression.
Competing Interests: N.T. reports having consultancy agreements with Marizyme, Mesentech, PulseData and Renibus; an ownership interest in ClinPredict, Klinrisk, Marizyme, Mesentech, PulseData, Quanta and Renibus; receiving research funding from AstraZeneca, Bayer, BI-Lilly, Janssen and Otsuka; receiving honoraria from AstraZeneca, Bayer, BI-Lilly, Janssen, Otsuka Pharmaceuticals and Pfizer; patents or royalties with Klinrisk and Marizyme; an advisory or leadership role with ClinPredict and Klinrisk; other interests or relationships with the National Kidney Foundation; and being the founder of ClinPredict and Klinrisk. T.F. reports personal fees from Baxter, ClinPredict, Quanta Dialysis Technologies and Strategic Health Resources, and personal fees/other from Klinrisk. S.J.L. reports personal fees from Quanta Dialysis Technologies. S.D.A. reports grants from Abbott Vascular and Vifor International, and personal fees from Amgen, AstraZeneca, Bayer, BioVentrix, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Impulse Dynamics, Janssen, Novartis, Occlutech, Respicardia, Servier, Vectorious and V-Wave. G.F. reports lecture fees and/or being a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier and Vifor Pharma. He is a senior consulting editor for JACC: Heart Failure and has received research support from the EU. B.P. reports consultant fees for AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, PhaseBio, Proton Intel, Sanofi/Lexicon, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; has stock options for Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Proton Intel, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; and holds a patent for site-specific delivery of eplerenone to the myocardium (US patent 9931412) and a provisional patent for histone acetylation-modulating agents for the treatment and prevention of organ injury (provisional patent US 63/045,784). P.R. reports personal fees from Bayer during the conduct of the study; research support and personal fees from AstraZeneca and Novo Nordisk and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi, and Vifor. All fees are given to Steno Diabetes Center Copenhagen. L.M.R. reports consultancy fees from Bayer. A.E.F. is a full-time employee of Bayer PL, Germany. Y.M.K.F. is a full-time employee of Bayer US. P.S. is a part-time employee of Bayer AG, Pharmaceuticals Division, Germany. R.L. and K.R. are full-time employees of Bayer AG, Pharmaceuticals Division, Germany. G.L.B. reports research funding, paid to the University of Chicago Medicine, from Bayer during the conduct of the study; research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; acted as a consultant and received personal fees from Alnylam, Merck and Relypsa; is an Editor of the American Journal of Nephrology, Nephrology and Hypertension, Section Editor of UpToDate and an Associate Editor of Diabetes Care and Hypertension Research.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
Methods: The validation cohort included all participants in FIDELITY up to 4 years. The primary and secondary composite outcomes included a ≥40% decrease in estimated glomerular filtration rate (eGFR) or kidney failure, and a ≥57% decrease in eGFR or kidney failure. Prediction discrimination was calculated using area under the receiver operating characteristic curve (AUC). Calibration plots were calculated by decile comparing observed with predicted risk.
Results: At time horizons of 2 and 4 years, 993 and 1795 patients experienced a primary outcome event, respectively. The model predicted the primary outcome accurately with an AUC of 0.81 for 2 years and 0.86 for 4 years. Calibration was appropriate at both 2 and 4 years, with Brier scores of 0.067 and 0.115, respectively. No evidence of interaction between treatment and risk was identified for the primary composite outcome ( P = .31).
Conclusions: Our findings demonstrate the accuracy and utility of a laboratory-based prediction model for early identification of patients at the highest risk of CKD progression.
Competing Interests: N.T. reports having consultancy agreements with Marizyme, Mesentech, PulseData and Renibus; an ownership interest in ClinPredict, Klinrisk, Marizyme, Mesentech, PulseData, Quanta and Renibus; receiving research funding from AstraZeneca, Bayer, BI-Lilly, Janssen and Otsuka; receiving honoraria from AstraZeneca, Bayer, BI-Lilly, Janssen, Otsuka Pharmaceuticals and Pfizer; patents or royalties with Klinrisk and Marizyme; an advisory or leadership role with ClinPredict and Klinrisk; other interests or relationships with the National Kidney Foundation; and being the founder of ClinPredict and Klinrisk. T.F. reports personal fees from Baxter, ClinPredict, Quanta Dialysis Technologies and Strategic Health Resources, and personal fees/other from Klinrisk. S.J.L. reports personal fees from Quanta Dialysis Technologies. S.D.A. reports grants from Abbott Vascular and Vifor International, and personal fees from Amgen, AstraZeneca, Bayer, BioVentrix, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Impulse Dynamics, Janssen, Novartis, Occlutech, Respicardia, Servier, Vectorious and V-Wave. G.F. reports lecture fees and/or being a committee member of trials and registries sponsored by Amgen, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier and Vifor Pharma. He is a senior consulting editor for JACC: Heart Failure and has received research support from the EU. B.P. reports consultant fees for AstraZeneca, Bayer, Boehringer Ingelheim, Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, PhaseBio, Proton Intel, Sanofi/Lexicon, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; has stock options for Brainstorm Medical, Cereno Scientific, G3 Pharmaceuticals, KBP Biosciences, Proton Intel, Sarfez, scPharmaceuticals, SQ Innovation, Tricida and Vifor/Relypsa; and holds a patent for site-specific delivery of eplerenone to the myocardium (US patent 9931412) and a provisional patent for histone acetylation-modulating agents for the treatment and prevention of organ injury (provisional patent US 63/045,784). P.R. reports personal fees from Bayer during the conduct of the study; research support and personal fees from AstraZeneca and Novo Nordisk and personal fees from Astellas, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, Sanofi, and Vifor. All fees are given to Steno Diabetes Center Copenhagen. L.M.R. reports consultancy fees from Bayer. A.E.F. is a full-time employee of Bayer PL, Germany. Y.M.K.F. is a full-time employee of Bayer US. P.S. is a part-time employee of Bayer AG, Pharmaceuticals Division, Germany. R.L. and K.R. are full-time employees of Bayer AG, Pharmaceuticals Division, Germany. G.L.B. reports research funding, paid to the University of Chicago Medicine, from Bayer during the conduct of the study; research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; acted as a consultant and received personal fees from Alnylam, Merck and Relypsa; is an Editor of the American Journal of Nephrology, Nephrology and Hypertension, Section Editor of UpToDate and an Associate Editor of Diabetes Care and Hypertension Research.
(© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)