title: Relation between Red Cell Distribution Width and Fibroblast Growth Factor 23 Cleaving in Patients with Chronic Kidney Disease and Heart Failure.
abstract: OBJECTIVE
  In chronic kidney disease (CKD), both anemia and deregulated phosphate metabolism are common and predictive of adverse outcome. Previous studies suggest that iron status influences phosphate metabolism by modulating proteolytic cleavage of FGF23 into C-terminal fragments. Red cell distribution width (RDW) was recently identified as a strong prognostic determinant for cardiovascular morbidity and mortality, independently of iron status. We assessed whether RDW is associated with FGF23 cleaving in CKD patients with heart failure.
  
  
  METHODS
  The associations between RDW and either intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23, reflecting iFGF23 and C-terminal fragments together) and the iFGF23/cFGF23 ratio were analyzed in 52 patients with CKD (eGFR 34,9 ± 13.9 ml/min/1.73m2) and chronic heart failure (CHF). Associations between RDW and FGF23 forms were studied by linear regression analysis adjusted for parameters of renal function, iron metabolism, phosphate metabolism and inflammation.
  
  
  RESULTS
  Median cFGF23 levels were 197.5 [110-408.5] RU/ml, median iFGF23 levels were 107.3 [65.1-162.2] pg/ml and median FGF23 ratio was 0.80 [0.37-0.86]. Mean RDW was 14.1 ± 1.2%. cFGF23 and RDW were associated (β = 1.63 x 10(-3), P < 0.001), whereas iFGF23 and RDW were not (β = -1.38 x 10(-3), P = 0.336). The iFGF23/cFGF23 ratio was inversely associated with RDW. The difference between cFGF23 and iFGF23 (cFGF23- iFGF23) was positively associated with RDW (β = 1.74 x 10(-3), P < 0.001). The association between cFGF23 and RDW persisted upon multivariable linear regression analysis, adjusted for parameters of renal function, phosphate metabolism, iron metabolism and inflammation (β = 0.97 x 10(-3), P = 0.047).
  
  
  CONCLUSIONS
  RDW is associated with cFGF23 but not with iFGF23 levels in patients with CKD and CHF. This suggests a connection between RDW and FGF23 catabolism, independent of iron status and inflammation. Future studies are needed to unravel underlying mechanisms and whether these pertain to the link between RDW and outcome.
authors.affiliation: Department of Nephrology and ICaR-VU, VUMC, Amsterdam, the Netherlands.
authors.forename: Fenna
authors.initials: F
authors.lastname: van Breda
authors.affiliation: Department of Cardiology, Ikazia Hospital, Rotterdam, the Netherlands.
authors.forename: Mireille E
authors.initials: ME
authors.lastname: Emans
authors.affiliation: Department of Internal Medicine, TerGooi Hospital, Hilversum, the Netherlands.
authors.forename: Karien
authors.initials: K
authors.lastname: van der Putten
authors.affiliation: Department of Medicine, division of Nephrology and Immunology, University of Alberta, Edmonton, Canada.
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
authors.affiliation: Department of Nephrology and ICaR-VU, VUMC, Amsterdam, the Netherlands.
authors.forename: Frans J
authors.initials: FJ
authors.lastname: van Ittersum
authors.affiliation: Department of Clinical Chemistry, Meander Medical Center, Amersfoort, the Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Kraaijenhagen
authors.affiliation: Department of Nephrology, UMCG, Groningen, the Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
authors.affiliation: Department of Nephrology and ICaR-VU, VUMC, Amsterdam, the Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Vervloet
authors.affiliation: Department of Nephrology, UMCG, Groningen, the Netherlands.
authors.forename: Carlo A J M
authors.initials: CA
authors.lastname: Gaillard
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D004909:Erythrocyte Indices; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood* / Q000150:complications* / Q000378:metabolism; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications* / Q000378:metabolism
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23