Fibroblast growth factor-23 and chronic allograft injury in pediatric renal transplant recipients: A Midwest Pediatric Nephrology Consortium study

Michael E. Seifert, Isa F. Ashoor, Myra L. Chiang, Aftab S. Chishti, Dennis J. Dietzen, Debbie S. Gipson, Halima S. Janjua, David T. Selewski, Keith A. Hruska

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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 m2 and biopsy-proven CRAI. Controls (n = 31) had transplant function >90 mL/min/1.73 m2 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 (r2 = -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.

Original languageEnglish (US)
Pages (from-to)378-387
Number of pages10
JournalPediatric Transplantation
Volume20
Issue number3
DOIs
StatePublished - May 1 2016
Externally publishedYes

Keywords

  • biomarkers
  • chronic allograft nephropathy
  • chronic rejection
  • pediatric kidney transplantation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Transplantation

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