1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with renal insufficiency

A reduced expression of the vitamin D receptor (VDR) in parathyroid glands of uremic animals and humans has been observed. Similar results have been obtained by our own group in peripheral blood mononuclear cells (PBMC) from patients with secondary hyperparathyroidism to chronic renal failure. However, the reasons for these changes are not clear. In the present study, we have investigated the specific uptake of [3H]1,25(OH)2D3 by PBMC of 11 women with advanced chronic renal failure (A-CRF), 6 women with mild-moderate renal insufficiency (M-CRF), and 23 healthy women. The mean dissociation constant (KD) was similar in both groups of patients and in healthy women (A-CRF: 0.7 +/- 0.5 x 10(-10) M; M-CRF: 1.1 +/- 0.9 x 10(-10) M; controls: 1.0 +/- 0.6 x 10(-10) M). However, VDR concentration was significantly decreased in A-CRF (0.8 +/- 0.5 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls, p < 0.001), whereas no changes were seen in M-CRF (1.7 +/- 0.7 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls). No correlation was seen between VDR and serum calcitriol or PTH levels, when considering both groups of patients together or separately. Conversely, a significant negative correlation was found between VDR and serum creatinine values when A-CRF and M-CRF were considered altogether (r = -0.63; p < 0.01). Treatment with two different schedules of oral calcitriol (five patients with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7 days) did not change VDR concentrations. We conclude that the low levels of serum 1,25(OH)2D3 of uremia are not responsible for the decrease in VDR concentration found in these patients.