title: Risk of ESRD and all cause mortality in type 2 diabetes according to circulating levels of FGF-23 and TNFR1.
abstract: BACKGROUND
  Recent studies demonstrated that circulating fibroblast growth factor (FGF)-23 was associated with risk of end stage renal disease (ESRD) and mortality. This study aims to examine whether the predictive effect of FGF-23 is independent from circulating levels of tumor necrosis factor receptor 1 (TNFR1), a strong predictor of ESRD in Type 2 diabetes (T2D).
  
  
  METHODS
  We studied 380 patients with T2D who were followed for 8-12 years and were used previously to examine the effect of TNFR1. Baseline plasma FGF-23 was measured by immunoassay.
  
  
  RESULTS
  During follow-up, 48 patients (13%) developed ESRD and 83 patients (22%) died without ESRD. In a univariate analysis, baseline circulating levels of FGF-23 and TNFR1 were significantly higher in subjects who subsequently developed ESRD or died without ESRD than in those who remained alive. In a Cox proportional hazard model, baseline concentration of FGF-23 was associated with increased risk of ESRD, however its effect was no longer significant after controlling for TNFR1 and other clinical characteristics (HR 1.3, p = 0.15). The strong effect of circulating level of TNFR1 on risk of ESRD was not changed by including circulating levels of FGF-23 (HR 8.7, p<0.001). In the Cox multivariate model, circulating levels of FGF-23 remained a significant independent predictor of all-cause mortality unrelated to ESRD (HR 1.5, p<0.001).
  
  
  CONCLUSIONS
  We demonstrated that the effect of circulating levels of FGF-23 on the risk of ESRD is accounted for by circulating levels of TNFR1. We confirmed that circulating levels of FGF-23 have an independent effect on all-cause mortality in T2D.
authors.affiliation: Research Division, Joslin Diabetes Center, Boston, Massachusetts, United States of America.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Tomohito
authors.initials: T
authors.lastname: Gohda
authors.forename: William H
authors.initials: WH
authors.lastname: Walker
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.forename: Adam M
authors.initials: AM
authors.lastname: Smiles
authors.forename: Rita R
authors.initials: RR
authors.lastname: Holak
authors.forename: Jackson
authors.initials: J
authors.lastname: Jeong
authors.forename: Kevin P
authors.initials: KP
authors.lastname: McDonnell
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Krolewski
authors.forename: Monika A
authors.initials: MA
authors.lastname: Niewczas
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications* / Q000401:mortality; D003928:Diabetic Nephropathies / Q000097:blood* / Q000209:etiology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000209:etiology*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23