title: Fibroblast growth factor 23 and incident CKD in type 2 diabetes.
abstract: OBJECTIVE
  High levels of fibroblast growth factor 23 are associated with accelerated progression of CKD. Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain.
  
  
  METHODS
  A prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial. The analytic sample consisted of a random subcohort of 590 patients with type 2 diabetes without prevalent CKD at baseline, 124 of whom developed incident CKD during follow-up, and 520 additional patients with incident CKD outside the random subcohort. The association between serum intact fibroblast growth factor 23 and incident CKD, defined as the new onset of eGFR<60 ml/min per 1.73 m(2) that represented a ≥25% decrease from baseline in an individual with eGFR≥60 ml/min per 1.73 m(2) and no microalbuminuria (<30 mg/g creatinine) at baseline, was tested.
  
  
  RESULTS
  The mean baseline eGFR in the random subcohort was 90.9±22.7 ml/min per 1.73 m(2). During a median follow-up of 4.7 years, there was a total of 644 patients with incident CKD. The median baseline fibroblast growth factor 23 level was modestly higher among patients with incident CKD versus controls (43.5, interquartile range=34.7-55.1 versus 39.8, interquartile range=31.9-49.5 pg/ml; P<0.001). Higher baseline fibroblast growth factor 23 levels were associated with higher risk of incident CKD in unadjusted and demographics-adjusted models, but the effect was attenuated after additional adjustment for clinical risk factors and baseline eGFR (hazard ratio per SD of natural log fibroblast growth factor 23, 1.09; 95% confidence interval, 0.94 to 1.27), which was the strongest predictor of incident CKD. Consistent with the results of primary analyses, baseline fibroblast growth factor 23 was not associated with eGFR slope.
  
  
  CONCLUSIONS
  Higher fibroblast growth factor 23 levels are not independently associated with higher risk of incident CKD in patients with type 2 diabetes.
authors.affiliation: Department of Medicine, Institute of Public Health and Medicine and tamara.isakova@northwestern.edu.
authors.forename: Tamara
authors.initials: T
authors.lastname: Isakova
authors.affiliation: Departments of Biostatistical Sciences and.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Craven
authors.affiliation: Department of Preventative Medicine, Division of Biostatistics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois;
authors.forename: Jungwha
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida; and.
authors.forename: Julia J
authors.initials: JJ
authors.lastname: Scialla
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida; and.
authors.forename: Huiliang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida; and.
authors.forename: Patricia
authors.initials: P
authors.lastname: Wahl
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Santica M
authors.initials: SM
authors.lastname: Marcovina
authors.affiliation: Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina;
authors.forename: Robert P
authors.initials: RP
authors.lastname: Byington
authors.affiliation: Department of Medicine, Institute of Public Health and Medicine and.
authors.forename: Myles
authors.initials: M
authors.lastname: Wolf
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: CKD; diabetes; diabetic nephropathy