Associations among erythropoietic, iron-related, and FGF23 parameters in pediatric kidney transplant recipients

• Published in: Pediatric nephrology (Berlin, West) Vol. 36; no. 10; pp. 3241 - 3249
• Main Authors: Limm-Chan, Blair, Wesseling-Perry, Katherine, Pearl, Meghan H., Jung, Grace, Tsai-Chambers, Eileen, Weng, Patricia L., Hanudel, Mark R.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2021; Springer; Springer Nature B.V
• Subjects: Adolescent; Age; Calcium; Child; Cross-Sectional Studies; Epidermal growth factor receptors; ErbB Receptors; Erythropoiesis; Erythropoietin; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Glomerular filtration rate; Health aspects; Hemoglobin; Hemoglobins; Hepcidin; Hepcidins; Humans; Inflammation; Iron; Iron in the body; Kidney diseases; Kidney transplantation; Kidney Transplantation - adverse effects; Kidney transplants; Kidneys; Measurement; Medicine; Medicine & Public Health; Mycophenolic acid; Nephrology; Original Article; Patients; Pediatric research; Pediatrics; Transplantation; Urology; What’s New in Renal Transplantation; United States; Pediatrics; Erythroferrone; Kidney transplant; Fibroblast growth factor 23; Anemia; Hepcidin
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-021-05081-0

Background In pediatric kidney transplant recipients, anemia is common and oftentimes multifactorial. Hemoglobin concentrations may be affected by traditional factors, such as kidney function and iron status, as well as novel parameters, such as fibroblast growth factor 23 (FGF23). Methods Here, we evaluated associations among erythropoietic, iron-related, and FGF23 parameters in a cohort of pediatric kidney transplant recipients, hypothesizing that multiple factors are associated with hemoglobin concentrations. Results In a cross-sectional analysis of 59 pediatric kidney transplant recipients (median (interquartile range) age 16.3 (13.5, 18.6) years, median estimated glomerular filtration rate (eGFR) 67 (54, 87) ml/min/1.73 m 2 ), the median age-related hemoglobin standard deviation score (SDS) was −2.1 (−3.3, −1.1). Hemoglobin SDS was positively associated with eGFR and calcium, and was inversely associated with erythropoietin (EPO), mycophenolate dose, and total, but not intact, FGF23. In multivariable analysis, total FGF23 remained inversely associated with hemoglobin SDS, independent of eGFR, iron parameters, EPO, and inflammatory markers, suggesting a novel FGF23-hemoglobin association in pediatric kidney transplant patients. In a subset of patients with repeat measurements, only delta hepcidin was inversely associated with delta hemoglobin SDS. Also, delta EPO positively correlated with delta erythroferrone (ERFE), and delta ERFE inversely correlated with delta hepcidin, suggesting a possible physiologic role for the EPO-ERFE-hepcidin axis in the setting of chronic kidney disease (CKD). Conclusion Our study provides further insight into factors potentially associated with erythropoiesis in pediatric kidney transplant recipients. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information