The Role of GDF-15 in Heart Failure Patients With Chronic Kidney Disease
Abstract
Background Growth differentiation factor-15 (GDF-15) is a stress-inducible cytokine and member of the transforming growth factor-β cytokine superfamily that refines prognostic assessment in subgroups of patients with heart failure (HF). We evaluated its role in HF patients with chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min/1.73 m 2).Methods A total of 358 patients with stable systolic HF were followed for a median of 1121 (interquartile range, 379-2600) days. Comprehensive evaluation including B-type natriuretic peptide (BNP) and GDF-15 testing was performed at study entry; the analysis was stratified according to kidney function.Results Patients with CKD (33.8%) were older, had more often diabetes, and were less often treated with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). GDF-15 was associated with estimated glomerular filtration rate, whereas BNP was associated with left ventricular-end diastolic diameter and ejection fraction (P < 0.01). During follow-up, 244 patients (68.2%) experienced an adverse outcome (death, urgent transplantation, implantation of mechanical circulatory support). In patients with HF and CKD, the Cox proportional hazard model identified BNP, GDF-15, sex, systolic blood pressure, sodium, total cholesterol, and ACEi/ARB treatment as significant variables associated with an adverse outcome (P < 0.05). In multivariable analysis, BNP was replaced by GDF-15. Net reclassification improvement confirmed prognostic superiority of the model encompassing GDF-15 (GDF-15, sodium, total cholesterol, ACEi/ARB treatment) compared with the model without GDF-15 (BNP, sex, sodium, ACEi/ARB treatment), net reclassification improvement 0.62, P = 0.005. In contrast, in patients with HF and normal kidney function, BNP remained superior to GDF-15 in a multivariable model.Conclusions In patients with systolic HF and CKD, GDF-15 is more strongly associated with adverse outcomes than the conventionally used BNP.
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Elevated circulating GDF-15 levels are associated with more severe disease or higher mortality in people with DM2, insulin resistance, hemodialysis, cachexia, cardiovascular diseases, COPD, VTE, cancer, or obesity.
“Elevated circulating GDF-15 levels have been associated with more severe disease or higher mortality in people with DM2, insulin resistance, hemodialysis, cachexia, cardiovascular diseases, chronic obstructive pulmonary disease (COPD), venous thromboembolism (VTE), cancer, or obesity (28–34).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [29]
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GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin
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- Authors
- Benes, J., Kotrc, M., Wohlfahrt, P., Conrad, M. J., Franekova, J., Jabor, A., Lupinek, P., Kautzner, J., Melenovsky, V., & Jarolim, P.
- Affiliations
- Charles University (CZ)
- Brigham and Women's Hospital (US)
- Institute of Clinical and Experimental Medicine (CZ)
- Venue
- Canadian Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 35
- Issue
- 4
- Pages
- 462-470
- ISSN
- 0828-282X (ISSN-L)
- OpenAlex
- W2906550469
- Cited by
- 42
- References
- 32
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 2
- FWCI
- 2.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Canadian Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Health (IN 00023001, 17-28784A)
- Czech Republic (15-14200)
- Biomarker Research and Clinical Trials Laboratory (103517)
- Abbott Laboratories
- Amgen
- AstraZeneca LP
- Beckman Coulter
- Daiichi Sankyo
- GlaxoSmithKline
- Merck
- Roche Diagnostics Corporation
- Takeda Global Research and Development Center
- Waters Technologies Corporation
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- growth differentiation factor 15, heart failure with reduced ejection fraction, chronic kidney disease, brain natriuretic peptide, prognostic factors, adverse outcomes, ACE inhibitors and angiotensin receptor blockers, net reclassification improvement, estimated glomerular filtration rate
- MeSH terms
- Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Cholesterol, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart-Assist Devices, Humans, Male, Middle Aged, Sex Factors, Sodium, Systole, Biomarkers, Proportional Hazards Models, Heart Transplantation, Natriuretic Peptide, Brain, Renal Insufficiency, Chronic, Heart Failure, Systolic, Growth Differentiation Factor 15, Angiotensin Receptor Antagonists
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