title: Intact FGF23 and α-Klotho during acute inflammation/sepsis in CKD patients.
abstract: BACKGROUND
  High FGF23 and low α-Klotho levels associate with systemic inflammation and reduced nitric oxide (NO) bioavailability, but the dynamics of this relationship in patients with CKD has not been investigated.
  
  
  METHODS
  We sequentially measured serum intact FGF23 and carboxyl-terminal (iFGF23, cFGF23), the iFGF23/cFGF23 ratio, αKlotho, biomarkers of inflammation (hs-CRP, IL-6 and TNF-α) and sepsis (procalcitonin), nitrotyrosine (reflecting NO synthesis and oxidative stress), serum iron and ferritin and CKD-MBD biomarkers, PTH, 25(OH)VD, 1,25(OH)2 VD at peak of intercurrent sepsis and after complete resolution in a series of 17 patients with CKD.
  
  
  RESULTS
  At peak infection, biomarkers of inflammation/sepsis, ferritin and nitrotyrosine were all very high (all P < 0·01) and declined towards the normal range thereafter (P < 0·01). iFGF23 was 191 ± 10 pg/ml (geometric mean, SD) and doubled to 371 ± 8 pg/ml (P = 0·003) after the resolution of infection, while cFGF23 did not change (246 ± 5 pg/mL vs. 248 ± 5 pg/mL, P = 0·50). As a consequence, the iFGF23/cFGF23 ratio, an indicator of the proteolytic cleavage of the FGF23 molecule, was 0·78 ± 3·87 at peak infection and increased to 1·49 ± 3·00 after resolution of infection (P < 0·001). In contrast, serum α-Klotho levels were upregulated at peak infection (peak infection: 526 ± 4 pg/ml, postinfection: 447 ± 4 pg/ml, P = 0·001). The eGFR, PTH and vitamin D did not change significantly throughout.
  
  
  CONCLUSIONS
  Acute inflammation/sepsis suppresses the active form of FGF23 and activates α-Klotho, the latter effect being likely attributable to enhance proteolysis of FGF23 molecule. iFGF23 downregulation and α-Klotho upregulation during acute sepsis may participate into the counter-regulatory response to severe inflammation in CKD patients with sepsis.
authors.affiliation: Department of Nephrology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Dounousi
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Torino
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pizzini
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cutrupi
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.|Renal Unit, Reggio Calabria, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Panuccio
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: D'Arrigo
authors.affiliation: Department of Epidemiology, Alexandria University, Alexandria, Egypt.
authors.forename: Samar
authors.initials: S
authors.lastname: Abd ElHafeez
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.|Renal Unit, Reggio Calabria, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.affiliation: Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR-IFC, Reggio Calabria, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000276:immunology; D002116:Calcitonin / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology; D007501:Iron / Q000378:metabolism; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010281:Parathyroid Hormone / Q000378:metabolism; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000276:immunology / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D010281:Parathyroid Hormone; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D; C002744:3-nitrotyrosine; D014443:Tyrosine; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002116:Calcitonin; D002097:C-Reactive Protein; D005293:Ferritins; C104450:25-hydroxyvitamin D; D007501:Iron; D005966:Glucuronidase; D000090265:Klotho Proteins; D002117:Calcitriol
keywords: Acute inflammation; Klotho; carboxy FGF23; chronic kidney disease; intact FGF23; sepsis