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2018 ; 13
(4
): e0196634
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gab.com Text
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Growth differentiation factor-15 and fibroblast growth factor-23 are associated
with mortality in type 2 diabetes - An observational follow-up study
#MMPMID29698460
Frimodt-Møller M
; von Scholten BJ
; Reinhard H
; Jacobsen PK
; Hansen TW
; Persson FI
; Parving HH
; Rossing P
PLoS One
2018[]; 13
(4
): e0196634
PMID29698460
show ga
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.