A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: Implications for PTH measurements in renal failure

In 8 adolescents with end-stage renal disease (ESRD), basal PTH concentrati ons measured with a novel immunoradiometric assay (IRMA) (Scantibodies Labo ratory, Inc.; S-IRMA) were invariably lower than those estimated with an es tablished assay (Nichols Institute; N-IRMA) (263 +/- 228 versus 645 +/- 442 pg/ml, respectively; p<0.00001). During in vivo dynamic testing, set point s for calcium-regulated PTB release were indistinguishable for both IRMAs ( 1.21 +/- 0.05 versus 1.22 +/- 0.06). However, maximal PTH concentrations we re significantly lower when measured by S-IRMA then by N-IRMA (557 +/- 448 and 1114 +/- 606 pg/ml, respectively); minimum PTH concentrations were 41 /- 65 pg/ml (5.0 +/- 4.2% of maximum) and 189 +/- 137 pg/ml (13.6 +/- 7.2% of maximum), respectively. Correlation between PTH and blood ionized calciu m indicated that PTH measured by S-IRMA decreased more readily than the con centrations determined by N-IRMA. The N-IRMA showed indistinguishable cross -reactivity with hPTH(1-84) and hPTH(7-84), while the S-IRMA detected only the full-length peptide. Furthermore, the radiolabeled detection antibody o f the N-IRMA interacted equivalently with hPTH(1-34) and hPTH(2-34), while the S-IRMA showed crossreactivity only with hPTH(1-34). These differences i n assay specificity could explain the observed differences in ESRD, and sug gest that PTH concentrations estimated by the S-IRMA reflect more accuratel y the amount of biologically active PTH in the circulation. Since low conce ntrations of PTH are frequently associated with adynamic bone disease, our findings may have significant implications for the treatment of renal osteo dystrophy with calcium and/or biologically active vitamin D analogs.