Influence of glomerular filtration rate on non-(1-84) parathyroid hormone (PTH) detected by intact PTH assays

Abstract

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(184) concentrations similar to those in the absence of renal failure. (C) 2000 American Association for Clinical Chemistry.