title: Circulating fibroblast growth factor 21 levels predict progressive kidney disease in subjects with type 2 diabetes and normoalbuminuria.
abstract: BACKGROUND
  Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy.
  
  
  METHODS
  Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis.
  
  
  RESULTS
  At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend <.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m(2), serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P < .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01-1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥ 60 mL/min/1.73 m(2) and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06-1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1-3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects.
  
  
  CONCLUSIONS
  Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.
authors.affiliation: Department of Medicine (C.H.L., E.Y.L.H., Y.C.W., C.Y.Y., W.S.C., M.M.A.Y., C.H.Y.F. A.X., K.S.L.L.), Queen Mary Hospital, Hong Kong SAR; Research Centre of Heart, Brain, Hormone and Healthy Aging (E.Y.L.H., A.X., K.S.L.L.), The University of Hong Kong, Pokfulam, Hong Kong SAR; and State Key Laboratory of Pharmaceutical Biotechnology (A.X., K.S.L.L.), The University of Hong Kong, Pokfulam, Hong Kong SAR.
authors.forename: C H
authors.initials: CH
authors.lastname: Lee
authors.forename: E Y L
authors.initials: EY
authors.lastname: Hui
authors.forename: Y C
authors.initials: YC
authors.lastname: Woo
authors.forename: C Y
authors.initials: CY
authors.lastname: Yeung
authors.forename: W S
authors.initials: WS
authors.lastname: Chow
authors.forename: M M A
authors.initials: MM
authors.lastname: Yuen
authors.forename: C H Y
authors.initials: CH
authors.lastname: Fong
authors.forename: A
authors.initials: A
authors.lastname: Xu
authors.forename: K S L
authors.initials: KS
authors.lastname: Lam
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000175:diagnosis; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012042:Registries
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors