Growth differentiation factor-15 and fibroblast growth factor-23 are associated with mortality in type 2 diabetes: An observational follow-up study
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- journal.pone.0196634
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OBJECTIVES: Two biomarkers, growth differentiation factor 15 (GDF-15) and fibroblast growth factor 23 (FGF-23)), reflecting different aspects of renal pathophysiology, were evaluated as determinants of decline in estimated glomerular filtration rate (eGFR), incident cardiovascular disease (CVD) and all-cause mortality in patients with type 2 diabetes (T2D) and microalbuminuria, but without clinical cardiac disease.
MATERIALS AND METHODS: Prospective study including 200 T2D patients. The predefined endpoint of chronic kidney disease (CKD) progression: A decline in eGFR of >30% at any time point during follow-up. Hazard ratios (HR) are provided per 1 SD increment of log2-transformed values.
RESULTS: Mean (± SD) age was 59 ± 9 years, eGFR 91.1 ± 18.3 ml/min/1.73m2 and median (IQR) UAER 103 (39-230) mg/24-h. During a median 6.1 years follow-up, 40 incident CVD events, 26 deaths and 42 patients reached the CKD endpoint after median 4.9 years. Higher GDF-15 was a determinant of decline in eGFR >30% and all-cause mortality in adjusted models (HR 1.7 (1.1-2.5); p = 0.018 and HR 1.9 (1.2-2.9); p = 0.003, respectively). Adding GDF-15 to traditional risk factors improved risk prediction of decline in renal function (relative integrated discrimination improvement (rIDI) = 30%; p = 0.037). Higher FGF-23 was associated with all-cause mortality in adjusted models (HR 1.6 (1.1-2.2); p = 0.011) with a rIDI of 30% (p = 0.024).
CONCLUSIONS: In patients with T2D and microalbuminuria, higher GDF-15 and FGF-23 were independently associated with all-cause mortality and higher GDF-15 improved risk prediction of decline in kidney function and higher FGF-23 of all-cause mortality, beyond traditional risk factors, but not independently of GDF-15.
Original language | English |
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Article number | e0196634 |
Journal | PLoS ONE |
Volume | 13 |
Issue number | 4 |
Number of pages | 13 |
ISSN | 1932-6203 |
DOIs | |
Publication status | Published - 2018 |
- Aged, Albuminuria/complications, Cardiovascular Diseases/diagnosis, Cause of Death, Diabetes Mellitus, Type 2/complications, Female, Fibroblast Growth Factors/blood, Follow-Up Studies, Glomerular Filtration Rate, Growth Differentiation Factor 15/blood, Humans, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, Renal Insufficiency, Chronic/diagnosis, Risk Factors
Research areas
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