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

• Published in: PloS one 2018-04, Vol.13 (4), p.e0196634-e0196634
• Main Authors: Frimodt-Møller, Marie, von Scholten, Bernt Johan, Reinhard, Henrik, Jacobsen, Peter Karl, Hansen, Tine Willum, Persson, Frederik Ivar, Parving, Hans-Henrik, Rossing, Peter
• Format: Article
• Language: English
• Subjects: Analysis; Biology and Life Sciences; Biomarkers; Cardiovascular diseases; Coronary artery disease; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Differentiation; Epidermal growth factor receptors; Fibroblast growth factor 23; Fibroblast growth factors; Glomerular filtration rate; Heart diseases; Kidneys; Mathematical models; Medicine and Health Sciences; Mortality; Patients; Renal function; Risk analysis; Risk factors; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0196634

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. 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. 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). 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.