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 chronicrenal failure, even before the uraemic phase and in the absenceof hypercalcaemia. Furthermore, a sigmoidal CT-calcium relationshipwas 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 evidentin renal patients with a variable degree of renal failure andin normal subjects; (b) whether the four secretory parametersalready described for the PTH-calcium relation curve might bedescribed for CT too; (c) whether any change in some, if any,of these secretory parameters could be found at a variable degreeof renal insufficiency. We studied 33 renal patients (RP), with a variable degree ofrenal failure (creatinine clearance ranging from 16 to 164ml/min),and 10 normal subjects (C). All RP and C were submitted to abasal evaluation including the assessment of (1) basal concentrationsof 1,25(OH)₂ vitamin D, 25(OH) vitamin D, mono-meric CT, intactPTH; (2) GFR by Cr⁵¹EDTA clearance. On the 2 subsequent days,a hypocalcaemic test (Na₂-EDTA about 37 mg/kg of body-weight/2h) and a hypercalcaemic test (Ca gluconate giving 8 mg/kg body-weight/2h of Ca element) were carried out for the assessment of bothCT and PTH secretory parameters. According to GFR values, theRP were divided into three groups: group RP1 (GFR > 70 ml/minper 1.73 m²; n = 10), group RP2 (GFR between 30 and 70 ml/minper 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 relationshipwas evident, opposite in direction to the PTH-calcium relationcurve. In these RP and C the four secretory parameters, characteristicfor the PTH-calcium secretion curve, were calculated for CTtoo. When pooled RP and C were considered, both minimal (9.0± 6.4 pg/ml) and maximal CT levels (71.8 ± 56.2pg/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 thecorresponding PTH secretory parameters (CT SP 1.39 ±0.08 mmol/1, PTH SP 1.23 ± 0.05 mmol/1,P<0.001) (CTSENS 243 ± 67%/mmol, PTH SENS 598 ± 329%, P<0.001).However, the CT SP values were strictly correlated with PTHSP values (r = 0.78, P<0.001). When CT secretory parameterswere considered separately in the RP groups, increased levelsof basal (36.1±28.6pg/ml), minimal (17.9±10.4),and maximal (139.9 ± 39.7) CT levels were found in theRP3 group, when compared with both the other RP groups and C.No significant difference was found as regards the CT SP andCT SENS values between RP and CT. These results suggest that (1) CT secretion is homeo-staticallycontrolled by calcium changes in the same range of the PTH-calciumsystem; (2) a sigmoidal CT-calcium relationship is demonstrablein most (but not all) RP and C; in these subjects it is possibleto calculate the CT secretory parameters as for PTH; (3) theincrease in CT levels in the course of chronic renal failureis quite similar to the already known increase of PTH, and ischaracterized by the increase of basal, minimal and maximalCT values, suggesting that an increased secretion of CT by thethyroid C-cells (rather than CT retention due to a decreasein renal function), is responsible for these findings.