title: Fibroblast growth factor-23 and chronic allograft injury in pediatric renal transplant recipients: a Midwest Pediatric Nephrology Consortium study.
abstract: The chronic kidney disease-mineral bone disorder (CKD-MBD) produces fibroblast growth factor-23 (FGF-23) and related circulating pathogenic factors that are strongly associated with vascular injury and declining kidney function in native CKD. Similarly, chronic renal allograft injury (CRAI) is characterized by vascular injury and declining allograft function in transplant CKD. We hypothesized that circulating CKD-MBD factors could serve as non-invasive biomarkers of CRAI. We conducted a cross-sectional, multicenter case-control study. Cases (n = 31) had transplant function >20 mL/min/1.73 m(2) and biopsy-proven CRAI. Controls (n = 31) had transplant function >90 mL/min/1.73 m(2) and/or a biopsy with no detectable abnormality in the previous six months. We measured plasma CKD-MBD factors at a single time point using ELISA. Median (range) FGF23 levels were over twofold higher in CRAI vs. controls [106 (10-475) pg/mL vs. 45 (8-91) pg/mL; p < 0.001]. FGF23 levels were inversely correlated with transplant function (r(2) = -0.617, p < 0.001). Higher FGF23 levels were associated with increased odds of biopsy-proven CRAI after adjusting for transplant function, clinical, and demographic factors [OR (95% CI) 1.43 (1.23, 1.67)]. Relationships between additional CKD-MBD factors and CRAI were attenuated in multivariable models. Higher FGF23 levels were independently associated with biopsy-proven CRAI in children.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Southern Illinois University, Springfield, IL, USA.|Department of Pediatrics, Washington University, St. Louis, MO, USA.
authors.forename: Michael E
authors.identifier: http://orcid.org/0000-0002-0557-6178
authors.initials: ME
authors.lastname: Seifert
authors.affiliation: Division of Nephrology, Children's Hospital of New Orleans, New Orleans, LA, USA.
authors.forename: Isa F
authors.initials: IF
authors.lastname: Ashoor
authors.affiliation: Department of Pediatrics, West Virginia University, Charleston, WV, USA.
authors.forename: Myra L
authors.initials: ML
authors.lastname: Chiang
authors.affiliation: Division of Nephrology, Hypertension and Renal Transplantation, University of Kentucky, Lexington, KY, USA.
authors.forename: Aftab S
authors.initials: AS
authors.lastname: Chishti
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO, USA.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Dietzen
authors.affiliation: Division of Nephrology, C.S. Mott Children's Hospital and University of Michigan, Ann Arbor, MI, USA.
authors.forename: Debbie S
authors.initials: DS
authors.lastname: Gipson
authors.affiliation: Center for Pediatric Nephrology, Cleveland Clinic Children's Hospital and Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Halima S
authors.initials: HS
authors.lastname: Janjua
authors.affiliation: Division of Nephrology, C.S. Mott Children's Hospital and University of Michigan, Ann Arbor, MI, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Selewski
authors.affiliation: Department of Pediatrics, Washington University, St. Louis, MO, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hruska
mesh_terms: D000293:Adolescent; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000379:methods*; D008297:Male; D015999:Multivariate Analysis; D009398:Nephrology / Q000379:methods*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23
keywords: biomarkers; chronic allograft nephropathy; chronic rejection; pediatric kidney transplantation