TY - JOUR
T1 - Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease
AU - Gutierrez, Orlando
AU - Isakova, Tamara
AU - Rhee, Eugene
AU - Shah, Anand
AU - Holmes, Julie
AU - Collerone, Gina
AU - Jüppner, Harald
AU - Wolf, Myles
PY - 2005
Y1 - 2005
N2 - Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal 1α-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D 3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (FePO4) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was <30. Increased FePO4 was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased FePO4. Increased FGF-23 and decreased 25(OH)D3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, FePO4, and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.
AB - Hyperphosphatemia, calcitriol deficiency, and secondary hyperparathyroidism (SHPT) are common complications of chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF-23) is a novel phosphaturic hormone that also inhibits renal 1α-hydroxylase activity and thus may be involved in the pathogenesis of SHPT. Several hypotheses were tested: that FGF-23 increases as renal function declines; is linearly associated with serum phosphate levels; is associated with increased phosphaturia independent of parathyroid hormone (PTH); and is associated with decreased calcitriol levels independent of renal function, hyperphosphatemia, and vitamin D stores. FGF-23, PTH, 25(OH)D 3, calcitriol, calcium, phosphate, and urinary fractional excretion of phosphate (FePO4) were measured in 80 CKD patients. Multiple linear regression was used to test the hypotheses. FGF-23 and PTH were inversely associated with estimated GFR (eGFR), whereas calcitriol levels were linearly associated with eGFR. Hyperphosphatemia and hypocalcemia were present in only 12 and 6% of patients, respectively, all of whose eGFR was <30. Increased FePO4 was associated with decreased eGFR, and both increased FGF-23 and PTH were independently associated with increased FePO4. Increased FGF-23 and decreased 25(OH)D3 were independent predictors of decreased calcitriol, but the effects on calcitriol levels of renal function itself and hyperphosphatemia were completely extinguished by adjusting for FGF-23. It is concluded that FGF-23 levels increase early in CKD before the development of serum mineral abnormalities and are independently associated with serum phosphate, FePO4, and calcitriol deficiency. Increased FGF-23 may contribute to maintaining normal serum phosphate levels in the face of advancing CKD but may worsen calcitriol deficiency and thus may be a central factor in the early pathogenesis of SHPT.
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U2 - 10.1681/ASN.2005010052
DO - 10.1681/ASN.2005010052
M3 - Article
C2 - 15917335
AN - SCOPUS:27744545673
SN - 1046-6673
VL - 16
SP - 2205
EP - 2215
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 7
ER -