title: Impact of fractional phosphate excretion on the relation of FGF23 with outcome in CKD patients.
abstract: BACKGROUND
  Cardiovascular risk is increased in patients with chronic kidney disease (CKD). Fibroblast growth factor 23 (FGF23) has emerged as an important, independent predictor of outcome in CKD patients. High FGF23 may, however, be a reflection of renal tissue resistance to its actions, reflected by low fractional excretion of phosphate (FePi). We evaluated the modifying effect of FePi on the association between FGF23 and outcome in patients with CKD stage 3-4.
  
  
  METHODS
  An analysis was performed in a subset of 166 adult patients of two participating centers of the MASTERPLAN trial of whom urine samples at baseline were available to calculate FePi. Outcome was defined as a composite of death, renal failure (defined as need for renal replacement therapy or doubling of serum creatinine) and cardiovascular events (myocardial infarction, cerebrovascular accident, percutaneous transluminal coronary angioplasty or coronary artery bypass graft. Patients were categorized by FGF23 and FePi. A product term was added to Cox regression and RERIs were calculated.
  
  
  RESULTS
  Patients had a median estimated glomerular filtration rate (eGFR) of 36 ml/min/1.73 m(2) [interquartile range (IQR) 27-44], serum phosphate 1.04 mmol/l (IQR 0.92-1.20), FGF23 140 RU/ml (IQR 81-236) and FePi 0.32 (IQR 0.25-0.44). A total of 96 events occurred during 5 years of follow up. LnFGF23 was a significant, independent predictor for the composite outcome [hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.53-2.95]. FePi did not modify the relation between FGF23 and outcome in these patients with CKD.
  
  
  CONCLUSIONS
  Our study shows that FGF23 itself, but not its renal tissue resistance as reflected by FePi, is an important risk factor for clinical events in subjects with CKD stage 3-4.
authors.affiliation: Department of Nephrology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, annekebech@hotmail.com.
authors.forename: Anneke P
authors.initials: AP
authors.lastname: Bech
authors.forename: Annet
authors.initials: A
authors.lastname: Bouma-de Krijger
authors.forename: Arjan D
authors.initials: AD
authors.lastname: van Zuilen
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.forename: Jan A J G
authors.initials: JA
authors.lastname: van den Brand
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: Jack F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000628:therapy; D003404:Creatinine / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands; D010710:Phosphates / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D065667:Renal Elimination; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003404:Creatinine