Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort
Open accessAbstract
Background/Aims: Cardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients. Methods: Among prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage. Results: The mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models. Conclusion: Higher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population.
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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 [33]
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- Authors
- You, A. S., Kalantar-Zadeh, K., Lerner, L., Nakata, T., Lopez, N., Lou, L., Veliz, M., Soohoo, M., Jing, J., Zaldivar, F., Gyuris, J., Nguyen, D. V., & Rhee, C. M.
- Affiliations
- University of California, Irvine (US)
- AVEO Oncology (United States) (US)
- ORCID
- Venue
- Cardiorenal Medicine
- Publisher
- S. Karger AG
- Published
- 2017
- Volume
- 7
- Issue
- 2
- Pages
- 158-168
- ISSN
- 1664-3828 (ISSN-L)
- 1664-5502
- PMC
- PMC5465654
- OpenAlex
- W2586988883
- Cited by
- 43
- References
- 42
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 3 · 2020: 8 · 2019: 4 · 2018: 5
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cardiorenal Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (UL1TR001414)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK092232, K23DK102903, DK102903, K24DK091419, R01DK092232)
- National Center for Advancing Translational Sciences (TR001414)
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- growth differentiation factor 15, GDF15, hemodialysis, all-cause mortality, protein-energy wasting, cardiovascular disease, biomarkers, serum creatinine, muscle mass, risk adjustment, end-stage renal disease
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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