The calcitonin-calcium relation curve and calcitonin secretory parameters in renal patients with variable degrees of renal function

Increased calcitonin (CT) levels have been reported in chronic renal failure, even before the uraemic phase and in the absence of hypercalcaemia. Furthermore, a sigmoidal CT-calcium relationship was recently observed in rats and haemodialysed patients. We carried out the present investigation in order to assess: (a) whether the sigmoidal CT-calcium relationship is also evident in renal patients with a variable degree of renal failure and in normal subjects; (b) whether the four secretory parameters already described for the PTH-calcium relation curve might be described for CT too; (c) whether any change in some, if any, of these secretory parameters could be found at a variable degree of renal insufficiency. We studied 33 renal patients (RP), with a variable degree of renal failure (creatinine clearance ranging from 16 to 164 ml/min), and 10 normal subjects (C). All RP and C were submitted to a basal evaluation including the assessment of (1) basal concentrations of 1,25(OH)2 vitamin D, 25(OH) vitamin D, monomeric CT, intact PTH; (2) GFR by Cr51EDTA clearance. On the 2 subsequent days, a hypocalcaemic test (Na2-EDTA about 37 mg/kg of body-weight/2 h) and a hypercalcaemic test (Ca gluconate giving 8 mg/kg body-weight/2 h of Ca element) were carried out for the assessment of both CT and PTH secretory parameters. According to GFR values, the RP were divided into three groups: group RP1 (GFR > 70 ml/min per 1.73 m2; n = 10), group RP2 (GFR between 30 and 70 ml/min per 1.73 m2; n = 15), group RP3 (GFR < 30 ml/min per 1.73 m2; n = 8). In most, but not all, RP and C a sigmoidal CT-calcium relationship was evident, opposite in direction to the PTH-calcium relation curve. In these RP and C the four secretory parameters, characteristic for the PTH-calcium secretion curve, were calculated for CT too. When pooled RP and C were considered, both minimal (9.0 +/- 6.4 pg/ml) and maximal CT levels (71.8 +/- 56.2 pg/ml) significantly differed from basal levels (24.3 +/- 18 pg/ml; P < 0.001). The CT set point (CT SP) and sensitivity (CT SENS) values were significantly higher and lower than the corresponding PTH secretory parameters (CT SP 1.39 +/- 0.08 mmol/l, PTH SP 1.23 +/- 0.05 mmol/l, P < 0.001) (CT SENS 243 +/- 67%/mmol, PTH SENS 598 +/- 329%, P < 0.001). However, the CT SP values were strictly correlated with PTH SP values (r = 0.78, P < 0.001). When CT secretory parameters were considered separately in the RP groups, increased levels of basal (36.1 +/- 28.6 pg/ml), minimal (17.9 +/- 10.4), and maximal (139.9 +/- 39.7) CT levels were found in the RP3 group, when compared with both the other RP groups and C. No significant difference was found as regards the CT SP and CT SENS values between RP and CT. These results suggest that (1) CT secretion is homeostatically controlled by calcium changes in the same range of the PTH-calcium system; (2) a sigmoidal CT-calcium relationship is demonstrable in most (but not all) RP and C; in these subjects it is possible to calculate the CT secretory parameters as for PTH; (3) the increase in CT levels in the course of chronic renal failure is quite similar to the already known increase of PTH, and is characterized by the increase of basal, minimal and maximal CT values, suggesting that an increased secretion of CT by the thyroid C-cells (rather than CT retention due to a decrease in renal function), is responsible for these findings.