Article open access publication

Growth differentiation factor-15 and fibroblast growth factor-23 are associated with mortality in type 2 diabetes – An observational follow-up study

PLoS ONE, Public Library of Science (PLoS), ISSN 1932-6203

Volume 13, 4, 2018

DOI:10.1371/journal.pone.0196634, Dimensions: pub.1103665739, PMC: PMC5919646, PMID: 29698460,



  1. (1) Steno Diabetes Center, grid.419658.7, Capital Region
  2. (2) Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  3. (3) Department of Medical Endocrinology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  4. (4) University of Copenhagen, grid.5254.6, KU






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.

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