Biomarkers of Kidney Failure and All-Cause Mortality in CKD

被引:0
作者
Onoja, Anthony [1 ]
McDonnell, Thomas [2 ,3 ]
Annessi, Isabelle [4 ]
Banks, Rosamonde E. [5 ]
Bergin, Marianne [6 ]
Cockwell, Paul [7 ]
Dusaulcy, Rodolphe [4 ]
Fraser, Simon D. S. [8 ]
Johnson, Tim [9 ]
Kalra, Philip A. [2 ,3 ]
Lemaitre, Barbara [4 ]
Saleem, Moin [10 ]
Skroblin, Philipp [11 ]
Soderberg, Magnus [12 ]
Taal, Maarten W. [13 ,14 ]
Unwin, Robert J. [15 ]
Vuilleumier, Nicolas [4 ]
Wheeler, David C. [16 ]
Geifman, Nophar [1 ]
机构
[1] Univ Surrey, Fac Hlth & Med Sci, Sch Hlth Sci, Guildford, England
[2] Salford Royal Hosp, Northern Care Alliance NHS Fdn Trust, Donal O Donoghue Renal Res Ctr, Salford, England
[3] Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, England
[4] Geneva Univ Hosp, Fac Med, Diagnost Dept, Div Lab Med, Geneva, Switzerland
[5] St James Univ Hosp, Leeds Inst Med Res, Sch Med, Leeds, England
[6] UCB Biopharm UK, Inflammatory Rheumatol FA, Slough, England
[7] Univ Hosp Birmingham, Queen Elizabeth Hosp, Inst Inflammat & Ageing, Dept Renal Med, Birmingham, England
[8] Univ Southampton, Sch Primary Care Populat Sci & Med Educ, Fac Med, Southampton, England
[9] Univ Sheffield, Med Sch, Expt Renal Med Human Metab & Oncol, Sheffield, England
[10] Univ Bristol, Bristol Med Sch, Bristol Renal & Childrens Renal Unit, Bristol, England
[11] Evotec Int GmbH, Gottingen, Germany
[12] AstraZeneca, Clin Pharmacol & Safety Sci, Pathol, R&D, Gothenburg, Sweden
[13] Univ Hosp Derby & Burton NHS Fdn Trust, Dept Renal Med, Derby, England
[14] Univ Nottingham, Ctr Kidney Res & Innovat, Sch Med, Acad Unit Translat Med Sci, Nottingham, England
[15] AstraZeneca Biopharmaceut, Cambridge Biomed Campus, Cambridge, England
[16] UCL, Dept Renal Med, London, England
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2025年
关键词
CKD; kidney failure; mortality; mortality risk; progression; progression of renal failure; CKD non-dialysis; ESKD; biomarkers; survival analysis; DISEASE; INJURY; ASSOCIATION; PROGRESSION; RISK;
D O I
10.1681/ASN.0000000767
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background CKD carries a variable risk for multiple adverse outcomes, highlighting the need for a personalized 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 per 1.73 m(2) or KRT), all-cause mortality, and a composite of both. Methods We included 2884 adults with nondialysis CKD from 16 nephrology centers across the United Kingdom. Twenty-one biomarkers associated with kidney damage, fibrosis, inflammation, and cardiovascular disease were analyzed 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 was 35 (25-47) ml/min per 1.73 m2, and the median urinary albumin-to-creatinine ratio was 197 (32-895) mg/g. During median 48 (33-55) months of follow-up, 680 kidney failure events and 414 all-cause mortality events occurred. For kidney failure, a model combining three biomarkers (soluble TNF receptor 1, soluble cluster of differentiation 40, and urinary collagen type 1 alpha 1 chain) showed good discrimination (C-index, 0.86; 95% confidence interval [CI], 0.83 to 0.89) but was outperformed by a model using established risk factors (age, sex, ethnicity, eGFR, and urinary albumin-to-creatinine ratio; C-index, 0.90; 95% CI, 0.88 to 0.92). For all-cause mortality, a model using three biomarkers (high-sensitivity cardiac troponin T, N-terminal pro-brain natriuretic peptide, and soluble urokinase plasminogen activator receptor) demonstrated equivalent discrimination (C-index, 0.80; 95% CI, 0.75 to 0.84) to an established risk factor model (C-index, 0.80; 95% CI, 0.76 to 0.84). For the composite outcome, the biomarker model discrimination (C-index, 0.78; 95% CI, 0.76 to 0.81) was numerically higher than for established risk factors (C-index, 0.77; 95% CI, 0.74 to 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 to 0.82; P value <0.01). Conclusions Risk prediction models incorporating novel biomarkers showed comparable discrimination to established risk factors of kidney failure and all-cause mortality.Clinical Trial registry name and registration number:ClinicalTrials.gov, NCT04084145.
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相关论文
共 32 条
[1]  
Agarwal A, 2020, CHRONIC RENAL DISEASE, 2ND EDITION, P263, DOI 10.1016/B978-0-12-815876-0.00018-8
[2]  
Chertow GM, 2024, NAT MED, V30, P2328, DOI 10.1038/s41591-024-03043-1
[3]   Potential role of soluble CD40 in the humoral immune response impairment of uraemic patients [J].
Contin, C ;
Pitard, V ;
Delmas, Y ;
Pelletier, N ;
Defrance, T ;
Moreau, JF ;
Merville, P ;
Déchanet-Merville, J .
IMMUNOLOGY, 2003, 110 (01) :131-140
[4]   Mechanisms underlying sCD40 production in hemodialysis patients [J].
Esposito, Pasquale ;
Rampino, Teresa ;
Gregorini, Marilena ;
Gabanti, Elisa ;
Bianzina, Stefania ;
Dal Canton, A. .
CELLULAR IMMUNOLOGY, 2012, 278 (1-2) :10-15
[5]  
F. London: National Institute for Health and Care Excellence (NICE), 2021, Evidence Review for the Best Combination of Measures to Identify Increased Risk of Progression in Adults, Children and Young People: Chronic Kidney Disease: Evidence Review
[6]   New Insights into Molecular Mechanisms of Chronic Kidney Disease [J].
Frak, Weronika ;
Kucmierz, Joanna ;
Szlagor, Magdalena ;
Mlynarska, Ewelina ;
Rysz, Jacek ;
Franczyk, Beata .
BIOMEDICINES, 2022, 10 (11)
[7]   Estimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes An Individual-Participant Data Meta-Analysis [J].
Grams, Morgan E. ;
Coresh, Josef ;
Matsushita, Kunihiro ;
Ballew, Shoshana H. ;
Sang, Yingying ;
Surapaneni, Aditya ;
de Pinho, Natalia Alencar ;
Anderson, Amanda ;
Appel, Lawrence J. ;
Arnlov, Johan ;
Azizi, Fereidoun ;
Bansal, Nisha ;
Bell, Samira ;
Bilo, Henk J. G. ;
Brunskill, Nigel J. ;
Carrero, Juan J. ;
Chadban, Steve ;
Chalmers, John ;
Chen, Jing ;
Ciemins, Elizabeth ;
Cirillo, Massimo ;
Ebert, Natalie ;
Evans, Marie ;
Ferreiro, Alejandro ;
Fu, Edouard L. ;
Fukagawa, Masafumi ;
Green, Jamie A. ;
Gutierrez, Orlando M. ;
Herrington, William G. ;
Hwang, Shih-Jen ;
Inker, Lesley A. ;
Iseki, Kunitoshi ;
Jafar, Tazeen ;
Jassal, Simerjot K. ;
Jha, Vivekanand ;
Kadota, Aya ;
Katz, Ronit ;
Koettgen, Anna ;
Konta, Tsuneo ;
Kronenberg, Florian ;
Lee, Brian J. ;
Lees, Jennifer ;
Levin, Adeera ;
Looker, Helen C. ;
Major, Rupert ;
Cohen, Cheli Melzer ;
Mieno, Makiko ;
Miyazaki, Mariko ;
Moranne, Olivier ;
Muraki, Isao .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2023, 330 (13) :1266-1277
[8]   Risk Factors for CKD Progression Overview of Findings from the CRIC Study [J].
Hannan, Mary ;
Ansari, Sajid ;
Meza, Natalie ;
Anderson, Amanda H. ;
Srivastava, Anand ;
Waikar, Sushrut ;
Charleston, Jeanne ;
Weir, Matthew R. ;
Taliercio, Jonathan ;
Horwitz, Edward ;
Saunders, Milda R. ;
Wolfrum, Katherine ;
Feldman, Harold, I ;
Lash, James P. ;
Ricardo, Ana C. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2021, 16 (04) :648-659
[9]   Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis [J].
Hill, Nathan R. ;
Fatoba, Samuel T. ;
Oke, Jason L. ;
Hirst, Jennifer A. ;
O'Callaghan, Christopher A. ;
Lasserson, Daniel S. ;
Hobbs, F. D. Richard .
PLOS ONE, 2016, 11 (07)
[10]   Tubulointerstitial injury and the progression of chronic kidney disease [J].
Hodgkins, Kavita S. ;
Schnaper, H. William .
PEDIATRIC NEPHROLOGY, 2012, 27 (06) :901-909