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1
Centre de Recherche et, Hôpital Saint-Luc, Montreal, Quebec H2X 1P1, Canada.
2
Département de Biochimie du CHUM, Hôpital
Saint-Luc, Montreal, Quebec H2X 1P1, Canada.
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Department of Medicine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
4
Department of Biochemistry,
Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
a Address correspondence to this author at: Centre de Recherche du CHUM, Hôpital Saint-Luc, 264 René Lévesque Blvd. East, Montréal, Québec H2X 1P1, Canada. Fax 514-281-2492; e-mail rechcalcium{at}ssss.gouv.qc.ca
Background: Commercial intact parathyroid hormone (I-PTH) assays detect molecular form(s) of human PTH, non-(1-84) PTH, different from the 84-amino acid native molecule. These molecular form(s) accumulate in hemodialyzed patients. We investigated the importance of non-(1-84) PTH in the interpretation of the increased I-PTH in progressive renal failure.
Methods: Five groups were studied: 26 healthy individuals, 12 hemodialyzed patients, and 31 patients with progressive renal failure subdivided according to their glomerular filtration rate (GFR) into 11 with a GFR between 60 and 100 mL · min-1 · 1.73 m-2, 12 with a GFR between 30 and 60 mL · min-1 · 1.73 m-2, and 8 with a GFR between 5 and 30 mL · min-1 · 1.73 m-2. We evaluated indicators of calcium and phosphorus metabolism and creatinine clearance (CrCl) in the progressive renal failure groups, and the HPLC profile of I-PTH and C-terminal PTH in all groups.
Results: Only patients with a GFR <30 mL · min-1 · 1.73 m-2 and hemodialyzed patients had decreased Ca2+ and 1,25-dihydroxyvitamin D, and increased phosphate. In patients with progressive renal failure, I-PTH was related to Ca2+ (r = -0.66; P <0.0001), CrCl (r = -0.61; P <0.001), 1,25-dihydroxyvitamin D (r = -0.40; P <0.05), and 25-hydroxyvitamin D (r = -0.49; P <0.01) by simple linear regression. The importance of non-(1-84) PTH in the composition of I-PTH increased with each GFR decrease, being 21% in healthy individuals, 32% in progressive renal failure patients with a GFR <30 mL · min-1 · 1.73 m-2, and 50% in hemodialyzed patients, with PTH(1-84) making up the difference.
Conclusions: As I-PTH increases progressively with GFR decrease, part of the increase is associated with the accumulation of non-(1-84) PTH, particularly when the GFR is <30 mL · min-1 · 1.73 m-2. Concentrations of I-PTH 1.6-fold higher than in healthy individuals are necessary in hemodialyzed patients to achieve PTH(1-84) concentrations similar to those in the absence of renal failure.
The following articles in journals at HighWire Press have cited this article:
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J. C. Estepa, I. Lopez, A. J. Felsenfeld, P. Gao, T. Cantor, M. Rodriguez, and E. Aguilera-Tejero Dynamics of secretion and metabolism of PTH during hypo- and hypercalcaemia in the dog as determined by the 'intact' and 'whole' PTH assays Nephrol. Dial. Transplant., June 1, 2003; 18(6): 1101 - 1107. [Abstract] [Full Text] [PDF]
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