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

TY - JOUR

T1 - Growth differentiation factor-15 and fibroblast growth factor-23 are associated with mortality in type 2 diabetes

T2 - An observational follow-up study

AU - Frimodt-Møller, Marie

AU - von Scholten, Bernt Johan

AU - Reinhard, Henrik

AU - Jacobsen, Peter Karl

AU - Hansen, Tine Willum

AU - Persson, Frederik Ivar

AU - Parving, Hans-Henrik

AU - Rossing, Peter

PY - 2018/4

Y1 - 2018/4

N2 - 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.

AB - 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.

KW - Aged

KW - Albuminuria/complications

KW - Cardiovascular Diseases/diagnosis

KW - Cause of Death

KW - Diabetes Mellitus, Type 2/complications

KW - Female

KW - Fibroblast Growth Factors/blood

KW - Follow-Up Studies

KW - Glomerular Filtration Rate

KW - Growth Differentiation Factor 15/blood

KW - Humans

KW - Incidence

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Proportional Hazards Models

KW - Renal Insufficiency, Chronic/diagnosis

KW - Risk Factors

U2 - 10.1371/journal.pone.0196634

DO - 10.1371/journal.pone.0196634

M3 - Journal article

C2 - 29698460

SN - 1932-6203

VL - 13

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

M1 - e0196634

ER -