ACCUMULATION OF A NON-(1-84) MOLECULAR-FORM OF PARATHYROID-HORMONE (PTH) DETECTED BY INTACT PTH ASSAY IN RENAL-FAILURE - IMPORTANCE IN THE INTERPRETATION OF PTH VALUES

A molecular form of PTH different from PTH-(1-84) and present in norma l serum is recognized by two-site intact (I-) PTH assays; it responds to Ca2+ changes in the same way that PTH carboxyl-terminal fragments d o. To evaluate the impact of this finding, we have compared basal, sti mulated, and nonsuppressible I-PTH values in 14 normal subjects and 15 renal failure patients, subdivided into 8 patients with low (<12 pmol /L; LBI) and 7 with high (>12 pmol/L; HBI) basal I-PTH. Samples obtain ed under various calcemic conditions in these 3 groups were further fr actionated by high performance liquid chromatography (HPLC) and assaye d for I-PTH, and the various peaks observed were quantitated by planim etry. Differences among the 3 groups were reinterpreted knowing the ex act composition of I-PTH. Basal I-PTH was greatly increased in HBI (me an +/- SD, 44.1 +/- 38.6 pmol/L) compared to that in normal subjects ( 2.5 +/- 0.8 pmol/L; P < 0.001) or LBI (6.1 +/- 2.4 pmol/L; P < 0.001); the difference was less in these last 2 groups (P < 0.01). Similar di fferences were observed for stimulated and nonsuppressible I-PTH, exce pt for stimulated I-PTH, which was similar in normal and LBI subjects. Two I-PTH HPLC molecular forms accounted for I-PTH immunoreactivity i n the 3 groups. In normal subjects, PTH-(1-84) accounted for 74.9 +/- 4.3%, 79.0 +/- 3.0%, and 87.2 +/- 1.0% of I-PTH in hyper-, normo-, and hypocalcemia, respectively, but only for 44.6 +/- 2.5%, 50.5 +/- 0.7% , and 63.6 +/- 0.1% in renal failure patients, with similar results in HBI and LBI. The accumulation of a non-(1-84) PTH peak accounted for the difference between normal subjects and renal failure patients. Whe n basal, stimulated, and nonsuppressible I-PTH values were separated i nto their 2 components, prior differences between HBI and LBI or norma l subjects remained unchanged because of very high I-PTH values in HBI , but differences between normal and LBI subjects were entirely explai ned by the accumulation of the non-(1-84) PTH peak [basal, 3.0 +/- 1.2 vs. 0.5 +/- 0.2 pmol/L (P < 0.001); stimulated, 6.8 +/- 2.3 vs. 2.3 /- 1.0 pmol/L (P < 0.001); nonsuppressible, 1.3 +/- 0.7 vs. 0.2 +/- 0. 08 pmol/L (P < 0.001)]; PTH-(1-84) values were similar (basal, 3.1 +/- 1.2 vs. 2.0 +/- 0.6 pmol/L; stimulated, 12.0 +/- 3.9 vs. 15.5 +/- 6.6 pmol/L; nonsuppressible, 1.1 +/- 0.6 vs. 0.52 +/- 0.22 pmol/L). Thus, a non-(1-84) PTH molecular form detected by two-site I-PTH assays acc umulates in renal failure and accounts for a larger proportion of I-PT H than that in normal subjects. Levels of I-PTH 1.57 times higher than those in normocalcemic subjects are thus required in renal failure to achieve similar PTH-(1-84) concentrations. The composition of I-PTH i s also identical in all hemodialyzed patients.