title: A non-(1-84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples.
abstract: We have previously shown that the Nichols assay for intact parathyroid hormone (I-PTH) reacts with a non-(1-84) molecular form of PTH. This form behaves as a carboxy-terminal fragment and accumulates in renal failure, accounting for 40-60% of the measured immunoreactivity. We wanted to see whether this was a common event with other commercial two-site I-PTH assays. We thus compared the ability of three commercial kits [Nichols (NL), Incstar (IT), and Diagnostic System Laboratories (DSL)] to measure I-PTH in 112 renal failure patients and to detect hPTH(1-84) and non-(1-84)PTH on HPLC profiles of serum pools from uremic patients with I-PTH concentrations of 10-100 pmol/L. The behavior of synthetic hPTH(7-84), a fragment possibly related to non-(1-84)PTH was also compared with hPTH(1-84) in the three assays. The I-PTH concentrations measured with the three assays in the 112 uremic samples were highly related (r2 > or = 0.89, P < 0.0001), and the values measured with NL were, on average, 23% higher than IT. Values measured with DSL were 23% and 56% higher than IT for values less than and more than 40 pmol/L, respectively. The three assays detected two HPLC peaks on four different profiles corresponding to hPTH(1-84) and non-(1-84)PTH. This last peak represented 36 +/- 8.4% of the immunoreactivity with NL, 24 +/- 5.5% with IT, and 25 +/- 2.8% with DSL (NL vs IT or DSL: P < 0.05). These differences were confirmed by a 50% lower immunoreactivity to hPTH(7-84) compared with hPTH(1-84) for IT and DSL but not for NL. These results suggest that most of the two-site I-PTH assays would cross-react with non-(1-84)PTH material, thus explaining about one-half of the 2-2.5 x higher I-PTH concentrations reported in uremic patients without bone involvement than in subjects without uremia.
authors.affiliation: Département de Biochimie, Université de Montréal, Quebec, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Lepage
authors.forename: L
authors.initials: L
authors.lastname: Roy
authors.forename: J H
authors.initials: JH
authors.lastname: Brossard
authors.forename: L
authors.initials: L
authors.lastname: Rousseau
authors.forename: C
authors.initials: C
authors.lastname: Dorais
authors.forename: C
authors.initials: C
authors.lastname: Lazure
authors.forename: P
authors.initials: P
authors.lastname: D'Amour
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006801:Humans; D010281:Parathyroid Hormone / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood; D011933:Reagent Kits, Diagnostic; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications; D014511:Uremia / Q000097:blood* / Q000209:etiology
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011933:Reagent Kits, Diagnostic