Biomarkers of Kidney Failure and All-Cause Mortality in CKD

Article Article scientifique Article Biomarkers of Kidney Failure and All-Cause Mortality in CKD eng 2025-06-20 author Onoja Anthony 0000-0002-1429-0032 School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey. author McDonnell Thomas 0000-0002-2898-4457 Donal O'Donoghue Renal Research Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK.,University of Manchester, Faculty of Biology Medicine and Health, Division of Cardiovascular Sciences, Oxford Rd, Manchester. author Annessi Ramseyer Isabelle Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals and Faculty of Medicine. 119833 author Banks Rosamonde E 0000-0002-0042-8715 Leeds Institute of Medical Research, St James's University Hospital, School of Medicine, Leeds, UK. author Bergin Marianne UCB Biopharma UK, Inflammatory Rheumatology FA, Slough, UK. author Cockwell Paul 0000-0003-1975-266 Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham, UK and Institute of Inflammation and Ageing, University of Birmingham, UK. author Dusaulcy Rodolphe Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals and Faculty of Medicine. 788845 author Fraser Simon D S 0000-0002-4172-4406 School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, UK. author Johnson Tim 0000-0003-2238-3463 Experimental Renal Medicine, Human Metabolism and Oncology, The Medical School, University of Sheffield, Sheffield, UK. author Kalra Philip A 0000-0001-7652-1572 Donal O'Donoghue Renal Research Centre, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, UK.,University of Manchester, Faculty of Biology Medicine and Health, Division of Cardiovascular Sciences, Oxford Rd, Manchester. author Lemaitre Barbara Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals and Faculty of Medicine. 649671 author Saleem Moin 0000-0002-9808-4518 Bristol Renal and Children's Renal Unit, Bristol Medical School, University of Bristol, Bristol, UK. author Skroblin Phillipp Evotec International GmbH, Göttingen, Germany. author Soderberg Magnus 0000-0003-0946-5202 Pathology, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden. author Taal Maarten W 0000-0002-9065-212 Department of Renal Medicine, University Hospitals of Derby and Burton NHS Foundation Trust.,Centre for Kidney Research and Innovation, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham. author Unwin Robert J 0000-0001-7839-6031 AstraZeneca Biopharmaceuticals, Cambridge Biomedical Campus, Cambridge, UK. author Vuilleumier Nicolas Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals and Faculty of Medicine. 61406 Département de médecine (DEMED) author Wheeler David C 0000-0003-0745-3478 Department of Renal Medicine, University College London, London, UK. author Geifman Nophar 0000-0003-2956-6676 School of Health Sciences, Faculty of Health and Medical Sciences, University of Surrey. 10.1681/ASN.0000000767 40540429 1046-6673 https://journals.lww.com/10.1681/ASN.0000000767 Background: Chronic kidney disease (CKD) carries a variable risk for multiple adverse outcomes, highlighting the need for a personalised approach. This study evaluated several novel biomarkers linked to key disease mechanisms to predict the risk of kidney failure (first event of eGFR <15 ml/min/1.73m2 or kidney replacement therapy), all-cause mortality, and a composite of both. Methods: We included 2,884 adults with non-dialysis CKD from 16 nephrology centres across the UK. Twenty-one biomarkers associated with kidney damage, fibrosis, inflammation, and cardiovascular disease were analysed in urine, plasma, or serum. Cox proportional hazards models were used to assess biomarker associations and develop risk prediction models. Results: Participants had mean age 63 (15) years, 58% were male and 87% White. Median eGFR 35 (25, 47) ml/min/1.73m2, and median urinary albumin-to-creatinine ratio (UACR) 197 (32, 895) mg/g. During median 48 (33, 55) months follow-up, 680 kidney failure events and 414 all-cause mortality events occurred. For kidney failure, a model combining three biomarkers (sTNFR1, sCD40, UCOL1A1) showed good discrimination (c-index 0.86, 95% CI: 0.83-0.89) but was outperformed by a model using established risk factors (age, sex, ethnicity, eGFR, UACR; c-index 0.90, 95% CI: 0.88-0.92). For all-cause mortality, a model using three biomarkers (hs-cTnT, NT-proBNP, suPAR) demonstrated equivalent discrimination (c-index 0.80, 95% CI: 0.75-0.84) to an established risk factor model (c-index 0.80, 95% CI: 0.76-0.84).For the composite outcome, the biomarker model discrimination (C-index 0.78, 95% CI: 0.76, 0.81) was numerically higher than for established risk factors (C-index 0.77, 95% CI: 0.74, 0.80), and the addition of biomarkers to the established risk factors led to a small but statistically significant improvement in discrimination (C-index 0.80, 95% CI: 0.77, 0.82; p value < 0.01). Conclusions: Risk prediction models incorporating novel biomarkers showed comparable discrimination to established risk factors for kidney failure and all-cause mortality. Dewey 616 Roche Diagnostics UCB Biopharma Evotec International GmbH AstraZeneca Travere Therapeutics 56 Département de médecine 221 false 211 Auto-immunité, inflammation et athérosclérose 270 Journal of the American Society of Nephrology 51071211-25ea-4914-92a7-58d1fcae1ce2 Article (Published version) Public biomarkers_of_kidney_failure_and_al.pdf 2687702 application/pdf CC BY-NC-ND-4.0 ebeae03add763592555b53686244b2216da8c8476ed59b9e52105ad1dc8acd02 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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