Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD

James B. Wetmore, Peter W. Santos, Jonathan D. Mahnken, Ron Krebill, Rochelle Menard, Hema Gutta, Leigh Quarles

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Context: The positive association of elevated fibroblast growth factor-23 (FGF23) with PTH levels in the setting of secondary hyperparathyroidism is paradoxical to the purported effects of FGF23 to suppress PTH secretion. Objective: We used dynamic calcium-mediated suppression of PTH levels in hemodialysis (HD) patients to determine the relationship between FGF23 levels and parathyroid gland function. Design: HD patients with elevated PTH were washed out of vitamin D analogs and/or calcimimetics and then exposed them to a high-calcium dialysate bath designed to suppress PTH. Setting: The study was conducted at an outpatient HD unit of an academic medical center. Participants: Eighteen maintenance HD patients with elevated PTH levels participated in the study. Main Outcome Measures: Ionized calcium (iCa), PTH, and FGF23 levels were measured during HD. The slope of the relationship between iCa and PTH (a marker of parathyroid gland mass) and the iCa level required for a 50% reduction in PTH were determined, and the association of these with FGF23 levels was determined. Results: Increased baseline log FGF23 levels were associated with putative alterations in gland mass as estimated by significantly shallower slopes of the iCa/PTH suppression curves (P = 0.0004), but there was no association between FGF23 and calcium sensing as measured by ionized Ca associated with a 50% suppression of PTH (P = 0.38). FGF23 levels decreased significantly during HD, but this change was not correlated with decrements in either renal phosphate or PTH. Conclusions: High FGF23 levels may be a marker for parathyroid gland hyperplasia in HD patients. Acute reductions in neither PTH nor renal phosphate during dialysis correlated with PTH suppression.

Original languageEnglish (US)
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Chronic Kidney Failure
Renal Dialysis
Calcium
Parathyroid Glands
Association reactions
Phosphates
Kidney
fibroblast growth factor 23
Secondary Hyperparathyroidism
Dialysis
Dialysis Solutions
Baths
Vitamin D
Hyperplasia
Outpatients
Maintenance
Outcome Assessment (Health Care)

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD. / Wetmore, James B.; Santos, Peter W.; Mahnken, Jonathan D.; Krebill, Ron; Menard, Rochelle; Gutta, Hema; Quarles, Leigh.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 96, No. 1, 01.01.2011.

Research output: Contribution to journalArticle

Wetmore, James B. ; Santos, Peter W. ; Mahnken, Jonathan D. ; Krebill, Ron ; Menard, Rochelle ; Gutta, Hema ; Quarles, Leigh. / Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD. In: Journal of Clinical Endocrinology and Metabolism. 2011 ; Vol. 96, No. 1.
@article{80858338bd494eb0b5fb691f826d5653,
title = "Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD",
abstract = "Context: The positive association of elevated fibroblast growth factor-23 (FGF23) with PTH levels in the setting of secondary hyperparathyroidism is paradoxical to the purported effects of FGF23 to suppress PTH secretion. Objective: We used dynamic calcium-mediated suppression of PTH levels in hemodialysis (HD) patients to determine the relationship between FGF23 levels and parathyroid gland function. Design: HD patients with elevated PTH were washed out of vitamin D analogs and/or calcimimetics and then exposed them to a high-calcium dialysate bath designed to suppress PTH. Setting: The study was conducted at an outpatient HD unit of an academic medical center. Participants: Eighteen maintenance HD patients with elevated PTH levels participated in the study. Main Outcome Measures: Ionized calcium (iCa), PTH, and FGF23 levels were measured during HD. The slope of the relationship between iCa and PTH (a marker of parathyroid gland mass) and the iCa level required for a 50{\%} reduction in PTH were determined, and the association of these with FGF23 levels was determined. Results: Increased baseline log FGF23 levels were associated with putative alterations in gland mass as estimated by significantly shallower slopes of the iCa/PTH suppression curves (P = 0.0004), but there was no association between FGF23 and calcium sensing as measured by ionized Ca associated with a 50{\%} suppression of PTH (P = 0.38). FGF23 levels decreased significantly during HD, but this change was not correlated with decrements in either renal phosphate or PTH. Conclusions: High FGF23 levels may be a marker for parathyroid gland hyperplasia in HD patients. Acute reductions in neither PTH nor renal phosphate during dialysis correlated with PTH suppression.",
author = "Wetmore, {James B.} and Santos, {Peter W.} and Mahnken, {Jonathan D.} and Ron Krebill and Rochelle Menard and Hema Gutta and Leigh Quarles",
year = "2011",
month = "1",
day = "1",
doi = "10.1210/jc.2010-1277",
language = "English (US)",
volume = "96",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Elevated FGF23 levels are associated with impaired calcium-mediated suppression of PTH in ESRD

AU - Wetmore, James B.

AU - Santos, Peter W.

AU - Mahnken, Jonathan D.

AU - Krebill, Ron

AU - Menard, Rochelle

AU - Gutta, Hema

AU - Quarles, Leigh

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Context: The positive association of elevated fibroblast growth factor-23 (FGF23) with PTH levels in the setting of secondary hyperparathyroidism is paradoxical to the purported effects of FGF23 to suppress PTH secretion. Objective: We used dynamic calcium-mediated suppression of PTH levels in hemodialysis (HD) patients to determine the relationship between FGF23 levels and parathyroid gland function. Design: HD patients with elevated PTH were washed out of vitamin D analogs and/or calcimimetics and then exposed them to a high-calcium dialysate bath designed to suppress PTH. Setting: The study was conducted at an outpatient HD unit of an academic medical center. Participants: Eighteen maintenance HD patients with elevated PTH levels participated in the study. Main Outcome Measures: Ionized calcium (iCa), PTH, and FGF23 levels were measured during HD. The slope of the relationship between iCa and PTH (a marker of parathyroid gland mass) and the iCa level required for a 50% reduction in PTH were determined, and the association of these with FGF23 levels was determined. Results: Increased baseline log FGF23 levels were associated with putative alterations in gland mass as estimated by significantly shallower slopes of the iCa/PTH suppression curves (P = 0.0004), but there was no association between FGF23 and calcium sensing as measured by ionized Ca associated with a 50% suppression of PTH (P = 0.38). FGF23 levels decreased significantly during HD, but this change was not correlated with decrements in either renal phosphate or PTH. Conclusions: High FGF23 levels may be a marker for parathyroid gland hyperplasia in HD patients. Acute reductions in neither PTH nor renal phosphate during dialysis correlated with PTH suppression.

AB - Context: The positive association of elevated fibroblast growth factor-23 (FGF23) with PTH levels in the setting of secondary hyperparathyroidism is paradoxical to the purported effects of FGF23 to suppress PTH secretion. Objective: We used dynamic calcium-mediated suppression of PTH levels in hemodialysis (HD) patients to determine the relationship between FGF23 levels and parathyroid gland function. Design: HD patients with elevated PTH were washed out of vitamin D analogs and/or calcimimetics and then exposed them to a high-calcium dialysate bath designed to suppress PTH. Setting: The study was conducted at an outpatient HD unit of an academic medical center. Participants: Eighteen maintenance HD patients with elevated PTH levels participated in the study. Main Outcome Measures: Ionized calcium (iCa), PTH, and FGF23 levels were measured during HD. The slope of the relationship between iCa and PTH (a marker of parathyroid gland mass) and the iCa level required for a 50% reduction in PTH were determined, and the association of these with FGF23 levels was determined. Results: Increased baseline log FGF23 levels were associated with putative alterations in gland mass as estimated by significantly shallower slopes of the iCa/PTH suppression curves (P = 0.0004), but there was no association between FGF23 and calcium sensing as measured by ionized Ca associated with a 50% suppression of PTH (P = 0.38). FGF23 levels decreased significantly during HD, but this change was not correlated with decrements in either renal phosphate or PTH. Conclusions: High FGF23 levels may be a marker for parathyroid gland hyperplasia in HD patients. Acute reductions in neither PTH nor renal phosphate during dialysis correlated with PTH suppression.

UR - http://www.scopus.com/inward/record.url?scp=78650871573&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650871573&partnerID=8YFLogxK

U2 - 10.1210/jc.2010-1277

DO - 10.1210/jc.2010-1277

M3 - Article

VL - 96

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -