title: Longitudinal FGF23 and Klotho axis characterization in children treated with chronic peritoneal dialysis.
abstract: BACKGROUND
  Fibroblast Growth Factor-23 (FGF23) and cofactor Klotho are key regulators of mineral metabolism in chronic kidney disease (CKD), but little is known about the mechanisms that regulate their production. This study evaluates longitudinal changes of FGF23 and Klotho levels and their regulatory factors in children on chronic peritoneal dialysis (PD).
  
  
  METHODS
  FGF23, Klotho, 25(OH) vitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) plasma concentrations were measured during 1 year of follow-up in PD children. Anthropometric and dialytical parameters were evaluated in addition to mineral metabolism variables.
  
  
  RESULTS
  Thirty-one patients under chronic PD were followed for 12 months. FGF23 mean plasma levels at Month 1 were significantly increased compared with controls, 215.1 ± 303.6 versus 9.4 ± 5.7 pg/mL, respectively (P < 0.001). Baseline Klotho levels were 41% lower in patients compared with controls, 132.1 ± 58 versus 320 ± 119.4 pg/mL, respectively (P < 0.001), and did not correlate with FGF23 and phosphorus levels. At Month 12, FGF23 (195 ± 300 pg/mL) and Klotho levels (130 ± 34 pg/mL) remained similar to baseline values. Log-FGF23 correlated significantly with height/age Z score (r= -0.38) and residual renal function (r = -0.44), but no correlation was found with serum phosphorus, phosphate intake, PTH and vitamin D levels. The log-FGF23 strongly correlated with calcium levels at Months 1, 6 and 12, however, this relationship was blunted if serum phosphorus was >6 mg/dL. By multiple regression analysis, calcium was the strongest variable determining FGF23 levels.
  
  
  CONCLUSIONS
  In this longitudinal study, FGF23 levels are markedly increased, and Klotho levels are reduced in PD children compared with controls. FGF23 levels appeared to be regulated primarily by serum calcium, showing a significant correlation at each time of measurement. This relationship was lost in patients with phosphorus >6 mg/dL. These observations may have important consequences to the therapeutic management of phosphate homeostasis in CKD patients.
authors: Division of Pediatric Nephrology , Luis Calvo Mackenna Children's Hospital, Faculty of Medicine, University of Chile , Santiago , Chile.
authors: Francisco J
authors: FJ
authors: Cano
authors: Division of Pediatric Nephrology , University of Miami Miller School of Medicine , Miami, FL , USA.
authors: Michael
authors: M
authors: Freundlich
authors: Division of Pediatric Nephrology , Luis Calvo Mackenna Children's Hospital, Faculty of Medicine, University of Chile , Santiago , Chile.
authors: Maria L
authors: ML
authors: Ceballos
authors: Division of Pediatric Nephrology , Luis Calvo Mackenna Children's Hospital, Faculty of Medicine, University of Chile , Santiago , Chile.
authors: Angelica P
authors: AP
authors: Rojo
authors: Division of Pediatric Nephrology , Luis Calvo Mackenna Children's Hospital, Faculty of Medicine, University of Chile , Santiago , Chile.
authors: Marta A
authors: MA
authors: Azocar
authors: Department of Biostatistics , Desarrollo University , Santiago , Chile.
authors: Iris O
authors: IO
authors: Delgado
authors: Division of Pediatric Nephrology , Luis Calvo Mackenna Children's Hospital, Faculty of Medicine, University of Chile , Santiago , Chile.
authors: Maria J
authors: MJ
authors: Ibacache
authors: Division of Pediatric Nephrology , Luis Calvo Mackenna Children's Hospital, Faculty of Medicine, University of Chile , Santiago , Chile.
authors: Maria A
authors: MA
authors: Delucchi
authors: Division of Pediatric Nephrology , Luis Calvo Mackenna Children's Hospital, Faculty of Medicine, University of Chile , Santiago , Chile.
authors: Ana M
authors: AM
authors: Lillo
authors: Department of Pediatric Endocrinology , Molecular Physiology Laboratory, Faculty of Medicine, Los Andes University , Santiago , Chile.
authors: Carlos E
authors: CE
authors: Irarrázabal
authors: Department of Pediatric Endocrinology , Molecular Physiology Laboratory, Faculty of Medicine, Los Andes University , Santiago , Chile.
authors: Maria F
authors: MF
authors: Ugarte
keywords: calcium; chronic kidney disease, FGF23, Klotho; phosphorus