THE SET-POINT OF PARATHYROID-HORMONE STIMULATION BY CALCIUM IS NORMALIN PROGRESSIVE RENAL-FAILURE

An increased set point of PTH stimulation by ionized calcium (Ca++) ha s been observed in renal failure patients with severe secondary hyperp arathyroidism. The extension of this concept to all renal failure pati ents has remained problematic, even if it could explain elevated PTH l evels in the absence of other biochemical abnormalities. We were parti cularly interested in seeing whether the concept could fit patients wi th progressive renal failure (PRF). To achieve this, we studied 26 nor mals (N), 9 patients with PRF, and 12 hemodialyzed patients (HD) in th e basal state and during parathyroid function tests. The latter two gr oups were studied at the end of winter and end of summer, respectively . Patients with PRF had normal levels of Ca++, PO4, and 1,25(OH)(2)D, and they had low-normal concentrations of 25(OH)D; their basal I- and C-PTH levels were 3- and 4-fold higher than N, as were their creatinin e levels. HD had significantly lower levels of Ca++ and 1,25(OH)(2)D, and they had higher levels of phosphate, creatinine, I-PTH, and C-PTH than N or PRF. Stimulated levels of I-PTH were similar in N (13.6 +/- 4.3 pmol/L) and PFR (18 +/- 3.3 pmol/L) and elevated in HD (37.1 +/- 2 8.7 pmol/L; P < 0.001 vs. N, and P < 0.05 vs. PRF). Nonsuppressible I- PTH was increased a-fold in PRF (N = 0.64 +/- 0.19 vs. PRF = 1.28 +/- 0.46 pmol/L; P < 0.01) and 6-fold in HD (3.95 +/- 2.85 pmol/L; P < 0.0 01 vs. others). But the set point of I-PTH stimulation by Ca++ was nor mal in PRF (N = 1.18 +/- 0.03 vs. PRF = 1.20 +/- 0.04 mmol/L; not sign ificant) and decreased in HD (1.09 +/- 0.04 mmol/L; P < 0.001 vs. othe rs). Similar results were obtained with the set point of C-PTH and of the C-PTH/I-PTH ratio. A positive correlation was observed between ser um Ca++ concentration and the set point value when all three populatio ns were analyzed together (r = 0.759, n = 47, P < 0.0001). These resul ts indicate that the set point of PTH stimulation is normal in PRF and decreased in hypocalcemic HD. The set point seems to adjust to the am bient Ca++ concentration of the patients, by mechanisms yet to be eluc idated. This does not suggest participation of this factor to the gene sis of the secondary hyperparathyroidism of PRF.