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).
BACKGROUND
Factors contributing to PTH resistance in dialysis patients remain elusive.


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


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


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


METHODS
Nineteen dialysis patients and 17 healthy volunteers were studied.


METHODS
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.


METHODS
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.
Wesseling-Perry
Katherine
K
David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095, USA. kwesseling@mednet.ucla.edu
Harkins
G Chris
GC
Wang
He-jing
HJ
Elashoff
Robert
R
Gales
Barbara
B
Horwitz
Mara J
MJ
Stewart
Andrew F
AF
Jüppner
Harald
H
Salusky
Isidro B
IB
D000293:Adolescent; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000097:blood* / Q000652:urine; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010281:Parathyroid Hormone / Q000502:physiology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000502:physiology*; D010758:Phosphorus / Q000097:blood; D006435:Renal Dialysis; D055815:Young Adult
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010446:Peptide Fragments; C414937:parathyroid hormone (7-84); D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium
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