The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84)

J Clin Endocrinol Metab. 2010 Jun;95(6):2772-80. doi: 10.1210/jc.2009-1909. Epub 2010 Apr 9.

Abstract

Context: Factors contributing to PTH resistance in dialysis patients remain elusive.

Objectives: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients.

Design: The study was a prospective, controlled assessment of response to PTH(1-34).

Setting: The study was performed at the University of California, Los Angeles, General Clinical Research Center.

Participants: Nineteen dialysis patients and 17 healthy volunteers were studied.

Intervention: PTH(1-34) was infused at a rate of 8 pmol/kg x h for 46 h. Bone biopsy was performed in all dialysis patients.

Main outcome measures: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion.

Results: Serum calcium levels rose in healthy volunteers (9.2 +/- 0.1 to 11.9 +/- 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 +/- 0.3 to 10.7 +/- 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 +/- 0.1 to 3.5 +/- 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 +/- 0.4 to 8.0 +/- 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover.

Conclusions: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Bone Development / drug effects
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Calcification, Physiologic / drug effects
  • Calcium / blood*
  • Calcium / urine
  • Female
  • Fibroblast Growth Factors / blood
  • Humans
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / pathology
  • Male
  • Parathyroid Hormone / physiology
  • Parathyroid Hormone / therapeutic use*
  • Peptide Fragments / physiology*
  • Phosphorus / blood
  • Renal Dialysis
  • Young Adult

Substances

  • Parathyroid Hormone
  • Peptide Fragments
  • parathyroid hormone (7-84)
  • Phosphorus
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • Calcium