Highlights
- •High circulating GDF-15 level correlates with CKD progression and poor prognosis.
- •Per 1 ng/mL increase in GDF-15 predicts a 31% increased risk of CKD progression.
- •Per 1 ng/mL GDF-15 increase predicts an average 55% increased risk of poor prognosis.
- •GDF-15 is linear to CKD progression and prognosis in a certain concentration range.
Abstract
Background
Patients with chronic kidney disease (CKD) typically exhibit circulating growth differentiation
factor-15 (GDF-15) at high levels. This meta-analysis aimed to evaluate the potential
value of GDF-15 in predicting CKD progression and prognosis. Furthermore, when sufficient
information was provided, the dose-response correlation was studied.
Methods
Studies were searched in Web of Science, Embase, and PubMed from inception until November
2022. By using random- or fixed-effects models, the pooled effect size was estimated
in accordance with heterogeneity in existing research.
Results
This study covered 14 studies from 12 articles with 7813 subjects participating in
the research. CKD patients in the top GDF-15 tertile had notably higher risks of CKD
progression (HR 2.60, 95% CI 2.06–3.27), all-cause mortality (HR 2.05, 95% CI 1.44–2.92),
cardiovascular mortality (HR 2.82, 95% CI 1.85–4.30), and cardiovascular events (HR
2.74, 95% CI 2.21–3.40), as compared to CKD patients in the bottom tertile. In the
dose-response study, the risks for CKD progression, all-cause death, cardiovascular
death, and cardiovascular events were increased by 31% (HR 1.31, 95% CI 1.06–1.61),
44% (HR 1.44, 95% CI 1.08–1.92), 67% (HR 1.67, 95% CI 1.37–2.03), and 55% (HR 1.55,
95% CI 1.31–1.83), respectively, with per 1 ng/mL increase in GDF-15. The positive
linear correlations between GDF-15 and CKD progression and prognosis in a certain
GDF-15 concentration range of approximately 0–3 ng/mL were indicated by the dose-response
curve.
Conclusions
Circulating GDF-15 independently predicted CKD progression and worse prognosis; however,
the predicted correlations may fall into a specific range of GDF-15 concentrations.
Keywords
Abbreviations:
CKD (chronic kidney disease), CVD (cardiovascular disease), ESRD (end-stage renal disease), eGFR (estimated glomerular filtration rate), GDF-15 (growth differentiation factor-15), MIC-1 (macrophage inhibitory cytokine-1), TGF-β (transforming growth factor β)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Costs and healthcare resource use associated with risk of cardiovascular morbidity in patients with chronic kidney disease: evidence from a systematic literature review.Adv Ther. 2021; 38: 994-1010
- Chronic kidney disease diagnosis and management: a review.JAMA. 2019; 322: 1294-1304
- Plasma and urine biomarkers in chronic kidney disease: closer to clinical application.Curr Opin Nephrol Hypertens. 2021; 30: 531-537
- Advances in the progression and prognosis biomarkers of chronic kidney disease.Front Pharmacol. 2021; 12785375
- The role of prognostic and predictive biomarkers for assessing cardiovascular risk in chronic kidney disease patients.Biomed Res Int. 2020; 20202314128
- GDF15 and growth control.Front Physiol. 2018; 9: 1712
- Growth differentiation factor 15: a novel biomarker with high clinical potential.Crit Rev Clin Lab Sci. 2019; 56: 333-350
- Pathophysiological role of growth differentiation factor 15 (GDF15) in obesity, cancer, and cachexia.Cytokine Growth Factor Rev. 2022; 64: 71-83
- Roles and regulation of growth differentiation factor-15 in the immune and tumor microenvironment.Hum Immunol. 2021; 82: 937-944
- Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury.Shock. 2005; 23: 543-548
- GDF15 as a central mediator for integrated stress response and a promising therapeutic molecule for metabolic disorders and NASH.Biochim Biophys Acta Gen Subj. 2021; 1865129834
- Growth differentiation factor-15 and risk of CKD progression.J Am Soc Nephrol. 2017; 28: 2233-2240
- Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach.Ups J Med Sci. 2020; 125: 37-43
- Cardiac biomarkers and risk of mortality in CKD (the CRIC Study).Kidney Int Rep. 2020; 5: 2002-2012
- Macrophage inhibitory cytokine-1 (MIC-1/GDF15) and mortality in end-stage renal disease.Nephrol Dial Transplant. 2012; 27: 70-75
- The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.Ann Intern Med. 2009; 151: W65-W94
- Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses.Eur J Epidemiol. 2010; 25: 603-605
- Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies.JAMA. 1998; 279: 1477-1482
- Methods for summarizing the risk associations of quantitative variables in epidemiologic studies in a consistent form.Am J Epidemiol. 1996; 144: 610-621
- Meta-analysis of epidemiologic dose-response data.Epidemiology. 1993; 4: 218-228
- Meta-analysis for linear and nonlinear dose-response relations: examples, an evaluation of approximations, and software.Am J Epidemiol. 2012; 175: 66-73
- Plasma growth differentiation factor-15 independently predicts all-cause and cardiovascular mortality as well as deterioration of kidney function in type 1 diabetic patients with nephropathy.Diabetes Care. 2010; 33: 1567-1572
- Association of growth differentiation factor 15 with mortality in a prospective hemodialysis cohort.Cardiorenal Med. 2017; 7: 158-168
- GDF-15, Galectin 3, soluble ST2, and risk of mortality and cardiovascular events in CKD.Am J Kidney Dis. 2018; 72: 519-528
- Cardiac biomarkers and risk of incident heart failure in chronic kidney disease: the CRIC (Chronic Renal Insufficiency Cohort) study.J Am Heart Assoc. 2019; 8e012336
- Cardiac and stress biomarkers and chronic kidney disease progression: the CRIC study.Clin Chem. 2019; 65: 1448-1457
- The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease.Atherosclerosis. 2020; 307: 11-15
- Serum growth differentiation factor-15 analysis as a malnutrition marker in hemodialysis patients.Turk J Med Sci. 2021; 51: 1984-1993
- A growth differentiation factor 15-based risk score model to predict mortality in hemodialysis patients.Diagnostics (Basel). 2021; 11: 286
- Major adverse cardiovascular events and mortality prediction by circulating GDF-15 in patients with type 2 diabetes: a systematic review and meta-analysis.Biomolecules. 2022; 12: 934
- A meta-analysis of growth differentiation factor-15 and prognosis in chronic heart failure.Front Cardiovasc Med. 2021; 8630818
- Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: a meta-analysis of prospective studies.Clin Cardiol. 2019; 42: 513-523
- Comorbidity in chronic kidney disease: a large cross-sectional study of prevalence in Scottish primary care.Br J Gen Pract. 2021; 71: e243-e2e9
- A long-term nationwide study on chronic kidney disease-related mortality in Italy: trends and associated comorbidity.J Nephrol. 2022; 35: 505-515
- Growth differentiation factor 15 protects against the aging-mediated systemic inflammatory response in humans and mice.Aging Cell. 2020; 19: e13195
- NAG-1/GDF15 protects against streptozotocin-induced type 1 diabetes by inhibiting apoptosis, preserving beta-cell function, and suppressing inflammation in pancreatic islets.Mol Cell Endocrinol. 2022; 549111643
- Growth differentiation factor-15 and its role in diabetes and cardiovascular disease.Cytokine Growth Factor Rev. 2021; 57: 11-18
- TFEB-GDF15 axis protects against obesity and insulin resistance as a lysosomal stress response.Nat Metab. 2021; 3: 410-427
- GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation.Circ Res. 2006; 98: 342-350
- Growth differentiation factor-15 deficiency augments inflammatory response and exacerbates septic heart and renal injury induced by lipopolysaccharide.Sci Rep. 2017; 7: 1037
- GDF15 is an inflammation-induced central mediator of tissue tolerance.Cell. 2019; 178 (1231-44.e11)
- Interpretation of tests of heterogeneity and bias in meta-analysis.J Eval Clin Pract. 2008; 14: 951-957
Article info
Publication history
Published online: February 03, 2023
Accepted:
January 22,
2023
Received in revised form:
December 26,
2022
Received:
November 29,
2022
Identification
Copyright
© 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
