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American Heart Association

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Final ID: MDP1233

Kidney and cardiac biomarkers and risk of adverse kidney outcomes in patients with type 2 diabetes and kidney disease, cardiovascular disease, or both

Abstract Body (Do not enter title and authors here): Introduction
Kidney (estimated glomerular filtration rate [eGFR] and urine albumin/creatinine ratio [UACR]) and cardiac biomarkers (high-sensitivity troponin T [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP] predict cardiovascular (CV) and kidney outcomes in a wide spectrum of patients. However, the discriminatory ability of these biomarkers in isolation and in combination is less clear.

Methods
We examined data from participants in the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE) with available baseline measurements (n=5,597). Cox models were fitted to explore the individual and collective discriminative ability of eGFR, log-UACR, log-NT-proBNP, and log-hsTnT with a kidney composite outcome (kidney failure [dialysis or transplant], kidney-related death, sustained doubling of serum creatinine). Subsequently, the combined biomarker model was additionally adjusted for clinical covariates (age, sex, race, BMI, insulin use, baseline BUN, history of stroke, amputation, or heart failure). Discriminatory capacity was assessed by differences in C-statistics.

Results
Over a median follow-up of 2.7 years, 344/5,597 (6.1%) participants experienced the kidney composite outcome. At baseline, mean eGFR was 52 ±23 mL/min/1.73m2; median baseline UACR, hsTnT, and NT-proBNP were 300 [62, 914]mg/g, 15 [7, 24]pg/mL and 176 [77, 430]pg/mL, respectively. For the kidney composite outcome, the C-statistic was 0.583 for eGFR alone, 0.622 for NT-proBNP, 0.686 for hsTnT, and 0.842 for UACR. The combined 4-biomarker model C-statistic was 0.847, which increased to 0.865 with the addition of clinical covariates (Table 1).

Conclusion
Among participants of ALTITUDE, higher UACR was the most important prognostic biomarker of future adverse kidney events, beyond that of a multivariable clinical model. The addition of eGFR, hsTnT, and NT-proBNP to UACR marginally improved model discrimination, with further improvement by adding clinical variables.
  • Mc Causland, Finnian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Vaduganathan, Muthiah  ( Brigham and Womens Hospital , Boston , Massachusetts , United States )
  • Pfeffer, Marc  ( BRIGHAM and WOMENS HOSPITAL , Boston , Massachusetts , United States )
  • Claggett, Brian  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Solomon, Scott  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Chaturvedi, Nishi  ( University College London , London , United Kingdom )
  • De Zeeuw, Dick  ( University Medical Center Groningen , Groningen , Netherlands )
  • Malachias, Marcus  ( INSTITUTO DE HIPERTENSAO , Belo Horizonte , Brazil )
  • Mcgrath, Martina  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • Mcmurray, John  ( BHF CARDIOVASCULAR RESEARCH CENTRE , Glasgow , United Kingdom )
  • Neuen, Brendon  ( George Institute for Global Health , Newtown , New South Wales , Australia )
  • Author Disclosures:
    Finnian Mc Causland: DO have relevant financial relationships ; Research Funding (PI or named investigator):Lexicon:Active (exists now) ; Other (please indicate in the box next to the company name):Rubin-Anders Scientific (expert witness):Active (exists now) ; Consultant:Zydus:Active (exists now) ; Consultant:GSK:Active (exists now) ; Research Funding (PI or named investigator):NIDDK:Active (exists now) ; Research Funding (PI or named investigator):Novartis:Active (exists now) | Muthiah Vaduganathan: DO have relevant financial relationships ; Researcher:received research grant support, served on advisory boards, or had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, BMS, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health, and participates on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics:Active (exists now) | Marc Pfeffer: DO have relevant financial relationships ; Consultant:Alexion, Alnylam, Apnimed, AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, DalCor, Intellia, Novartis, and Novo Nordisk. :Active (exists now) ; Individual Stocks/Stock Options:Dal-Cor:Active (exists now) ; Researcher:Lexicon, Novartis:Past (completed) | Brian Claggett: DO have relevant financial relationships ; Consultant:Cardior:Active (exists now) ; Consultant:Eli Lilly:Active (exists now) ; Consultant:CVRx:Past (completed) ; Consultant:Intellia:Active (exists now) ; Consultant:Cytokinetics:Past (completed) ; Consultant:Cardurion:Active (exists now) | Scott Solomon: DO have relevant financial relationships ; Research Funding (PI or named investigator):Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly,NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, US2.AI:Active (exists now) ; Consultant:Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Intellia, Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, Valo:Active (exists now) | Nishi Chaturvedi: No Answer | Dick de Zeeuw: No Answer | Marcus Malachias: No Answer | Martina McGrath: DO have relevant financial relationships ; Research Funding (PI or named investigator):Lexicon:Active (exists now) ; Consultant:Alexion:Past (completed) | John McMurray: DO have relevant financial relationships ; Research Funding (PI or named investigator):British Heart Foundation, National Institute for Health – National Heart Lung and Blood Institute (NIH-NHLBI), Boehringer Ingelheim, SQ Innovations, Catalyze Group. - Payment to Glasgow University:Active (exists now) ; Other (please indicate in the box next to the company name):KBP Biosciences - My employer, Glasgow University, has been paid by KBP Biosciences for my time spent scientific advisor to company to help guide clinical development in cardio-renal disease, inflammation & infection.:Past (completed) ; Consultant:WIRB-Copernicus Group Clinical Inc. - Data Safety Monitoring Board:Active (exists now) ; Other (please indicate in the box next to the company name):Bayer - My employer, Glasgow University, has been paid by Bayer for my time spent as Steering Committee member for the PANACHE trial using neladenoson bialanate and for the FINEARTS trial with finerenone. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/drugs.:Active (exists now) ; Other (please indicate in the box next to the company name):Glaxo Smith Kline - My employer, Glasgow University, has been paid by GSK for my time spent as Co-principal investigator and Steering Committee member, respectively, for the Harmony-Outcomes trial (albiglutide) and two trials, ASCEND-D and ASCEND-ND, using daprodustat, and meetings related to these trials. GSK has also paid my travel and accommodation for some of these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/drugs.:Active (exists now) ; Other (please indicate in the box next to the company name):Novartis - My employer, Glasgow University, has been paid by Novartis for my time spent as Executive Committee member and then co-principal investigator of ATMOSPHERE, co-principal investigator of the PARADIGM-HF and PARAGON-HF trials and Executive/Steering Committee member for PARADISE-MI, PERSPECTIVE and PARACHUTE-HF trials (with sacubitril/valsartan) and meetings/presentations related to these trials and aliskiren and sacubitril/valsartan. Novartis has also paid my travel and accommodation for some of these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments from Novartis in relation to these trials/drugs.:Active (exists now) ; Other (please indicate in the box next to the company name):Cardurion - My employer, Glasgow University, has been paid by Cardurion for my participation in a company advisory board about development of a PDE 9 inhibitor in heart failure.:Active (exists now) ; Consultant:Global Clinical Trial Partners Ltd. - Director:Active (exists now) ; Consultant:Alynylam Pharmaceuticals, Amgen, AnaCardio, AstraZeneca, Bayer, Berlin Cures, BMS, Cardurion, Cytokinetics, Ionis Pharmaceuticals, Novartis, Regeneron Pharmaceuticals, River 2 Renal Corp.:Active (exists now) ; Other (please indicate in the box next to the company name):Theracos - My employer, Glasgow University, has been paid by Theracos for my time spent as Principal investigator for the BEST trial and meetings related to this trial. Theracos has also paid my travel and accommodation for some of these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to this trial/this drug.:Past (completed) ; Other (please indicate in the box next to the company name):Amgen - My employer, Glasgow University, has been paid by Amgen for my time spent as Steering Committee member for the ATOMIC-HF, COSMIC-HF and GALACTIC-HF trials and meetings and other activities related to these trials. Amgen has also paid my travel and accommodation for some of these meetings/activities. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/this drug.:Active (exists now) ; Other (please indicate in the box next to the company name):Cytokinetics - My employer, Glasgow University, has been paid by Cytokinetics for my time spent as Steering Committee member for the ATOMIC-HF, COSMIC-HF and GALACTIC-HF trials and meetings and other activities related to these trials. Cytokinetics has also paid my travel and accommodation for some of these meetings/activities. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to these trials/this drug.:Active (exists now) ; Speaker:Abbott, Alkem Metabolics, Astra Zeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharmaceuticals Ltd., Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharmaceuticals, J.B. Chemicals & Pharmaceuticals Ltd., Lupin Pharmaceuticals, Medscape/Heart.Org., ProAdWise Communications, Radcliffe Cardiology, Sun Pharmaceuticals, The Corpus, Translation Research Group, Translational Medicine Academy - personal lecture fees:Active (exists now) ; Other (please indicate in the box next to the company name):AstraZeneca - My employer, Glasgow University, has been paid by AstraZeneca (who market dapagliflozin) for my time spent as Principal Investigator of DAPA-HF and Co-principal Investigator of DELIVER and DETERMINE (trials using dapagliflozin) in heart failure and meetings and other activities related to these trials. AstraZeneca has also paid my travel and accommodation for these meetings. These payments were made through a Consultancy with Glasgow University and I have not received personal payments in relation to this trial/this drug.:Active (exists now) | Brendon Neuen: DO have relevant financial relationships ; Consultant:AstraZeneca:Active (exists now) ; Research Funding (PI or named investigator):Menarini:Expected (by end of conference) ; Consultant:Travere Therapeutics:Active (exists now) ; Consultant:Novo Nordisk:Active (exists now) ; Consultant:Boehringer and Ingelheim:Active (exists now) ; Consultant:Bayer:Active (exists now) ; Consultant:Alexion:Active (exists now)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Cardiovascular-Kidney-Metabolic Health- Biomarkers and Imaging in the Era of Precision Medicine

Sunday, 11/17/2024 , 09:30AM - 10:45AM

Moderated Digital Poster Session

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