Renal mass and reserve of vitamin D: Determinants in primary hyperparathyroidism

Abstract

We studied circulating 1,25(OH)2D3 and its determinants in 102 patients with primary hyperparathyroidism (PHPT), 33 of them with recurrent renal stones, 60 with non-specific symptoms, and nine with overt bone disease. Means for serum 1,25(OH)2D3 and intestinal absorption of calcium were abnormally high in the renal stone group, slightly elevated in the non-specific group, and low-normal in the bone disease group. In the whole population of patients, we found a positive correlation between circulating 1,25(OH)2D3 and creatinine clearance (taken as an index of the functional renal mass). Negative correlations were observed between 1,25(OH)2D3 and age, and between creatinine clearance and age, the latter being not different from that observed in a normal large population. In the renal stone group, means for the determinants of the renal 1 alpha hydroxylase activity, that is, PTH activity expressed as nephrogenous cyclic AMP (NcAMP), serum phosphate and calcium were identical to those of the group with non-specific symptoms. However means for age were lower and functional renal mass significantly higher in the renal stone group, which may account for the higher value of circulating 1,25(OH)2D3. In the bone disease group, means for age, renal mass and serum calcium were identical to those of the group with non-specific symptoms, and NcAMP was far higher and hypophosphatemia more marked, which may not account for the lower value of circulating 1,25(OH)2D3. However, in the bone disease group, serum 25(OH)D was abnormally low, which may limit the renal production of 1,25(OH)2D3 and explain the low-normal circulating values. From these results, we suggest that the renal mass and vitamin D reserve might be two major determinants of the circulating values of 1,25(OH)2D3, and of the clinical presentation of PHPT. In young patients with high renal mass, PTH hypersecretion would result in a very large production of 1,25(OH)2D3, and thus very high intestinal absorption of calcium, hypercalciuria and high risk of renal stones. In older patients, with lower renal mass and normal reserve of vitamin D, a similar degree of PTH hypersecretion would result in a slightly elevated 1,25(OH)2D3, and thus high-normal intestinal absorption of calcium and calciuria, and low risk of renal stones. In older patients with vitamin D deficiency, the low-normal 1,25(OH)2D3, low intestinal absorption of calcium, and far higher degree of PTH hypersecretion may explain the occurrence of over bone disease.