TY - JOUR
T1 - Abnormalities in renal tubular phosphate handling in children with sickle cell disease
AU - Raj, Vimal Master Sankar
AU - Freundlich, Michael
AU - Hamideh, Dima
AU - Alvarez, Ofelia
AU - Seeherunvong, Wacharee
AU - Abitbol, Carolyn
AU - Katsoufis, Chryso
AU - Chandar, Jayanthi
AU - Ruiz, Phillip
AU - Zilleruelo, Gaston
N1 - Publisher Copyright:
© 2014 Wiley Periodicals, Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background: The mechanisms responsible for the hyperphosphatemia in patients with sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic hormone has not been investigated in SCD. Hence, we evaluated parameters of renal tubular phosphorus handling and their relation to prevailing FGF23 levels in a cohort of young SCD patients. Methods: Renal tubular phosphate handling and circulating levels of various analytes including FGF23 and parathyroid hormone (PTH) were measured in 24 children with SCD and normal estimated GFR in a cross sectional study. Correlation and regression analysis were employed to derive relationships between serum phosphorus and several variables. Results: Most children showed elevated age- adjusted serum phosphorus (5.1±0.7mg/dl) levels. Tubular re-absorption of phosphorus(TRP) (96.3±2.1%) and tubular maximum re-absorption of phosphorus per unit volume of GFR (TMP/GFR) (4.9±0.6mg/dl) were both elevated. Plasma intact FGF23 concentrations were elevated (81±38pg/ml) while the average PTH values were normal in most patients (50±27pg/ml). Univariate analysis showed significant correlations of serum phosphorus with TMP/GFR, alkaline phosphatase, age, lactate dehydrogenase (LDH), and log intact FGF23. TMP/GFR correlated with log intact FGF23 (r=0.5, P< or =0.01) but not with PTH. Multiple regression analysis yielded an independent relationship of serum phosphorus with TMP/GFR. Conclusion: The elevated serum phosphorus concentrations with simultaneously increased TMP/GFR and elevated FGF23 levels collectively suggest that patients with SCD display proximal tubular resistance to the action of FGF23 before any decline in GFR.
AB - Background: The mechanisms responsible for the hyperphosphatemia in patients with sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic hormone has not been investigated in SCD. Hence, we evaluated parameters of renal tubular phosphorus handling and their relation to prevailing FGF23 levels in a cohort of young SCD patients. Methods: Renal tubular phosphate handling and circulating levels of various analytes including FGF23 and parathyroid hormone (PTH) were measured in 24 children with SCD and normal estimated GFR in a cross sectional study. Correlation and regression analysis were employed to derive relationships between serum phosphorus and several variables. Results: Most children showed elevated age- adjusted serum phosphorus (5.1±0.7mg/dl) levels. Tubular re-absorption of phosphorus(TRP) (96.3±2.1%) and tubular maximum re-absorption of phosphorus per unit volume of GFR (TMP/GFR) (4.9±0.6mg/dl) were both elevated. Plasma intact FGF23 concentrations were elevated (81±38pg/ml) while the average PTH values were normal in most patients (50±27pg/ml). Univariate analysis showed significant correlations of serum phosphorus with TMP/GFR, alkaline phosphatase, age, lactate dehydrogenase (LDH), and log intact FGF23. TMP/GFR correlated with log intact FGF23 (r=0.5, P< or =0.01) but not with PTH. Multiple regression analysis yielded an independent relationship of serum phosphorus with TMP/GFR. Conclusion: The elevated serum phosphorus concentrations with simultaneously increased TMP/GFR and elevated FGF23 levels collectively suggest that patients with SCD display proximal tubular resistance to the action of FGF23 before any decline in GFR.
KW - Estimated glomerular filtration rate
KW - Fibroblast growth factor 23
KW - Intact parathyroid hormone
KW - Sickle cell disease
KW - Tubular maximum re-absorption of phosphorus per unit of GFR
KW - Tubular re-absorption of phosphorus
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U2 - 10.1002/pbc.25188
DO - 10.1002/pbc.25188
M3 - Article
C2 - 25132581
AN - SCOPUS:84911463826
VL - 61
SP - 2267
EP - 2270
JO - Medical and Pediatric Oncology
JF - Medical and Pediatric Oncology
SN - 1545-5009
IS - 12
ER -