1,25-dihydroxyvitamin D-3 receptors in peripheral blood mononuclear cells from patients with renal insufficiency

A reduced expression of the vitamin D receptor (VDR) iir 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. Howe ver; the reasons for these changes are not clear: In the present study we h ave investigated the specific uptake of [H-3]1,25(OH)(2)D-3 by BMC of II wo men with advanced chronic renal failure (A-CRF), 6 women with mild-moderate renal insufficiency (M-CRF), and 23 healthy women. The mean dissociation c onstant (K-D) was similar in both groups of patients and ill 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 decre ased in A-CRF (0.8 +/- 0.5 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cell s in controls, p < 0.001), whereas no changes were seen in M-CRF(1.7 +/- 0. 7 fmo/10(7) cells cs. 2.3 +/- 0.9 fmol/10(7) cells in controls). No correla tion was seen between VDR and serum calcitriol oi PTH levels, when consider ing both groups of patients together or separately Conversely, a significan t negative con-elation was found between VDR and serum creatinine values wh en A-CRF and M-CRF were considered altogether (r = -0.63; p <0.01). Treatme nt with two different schedules of oral calcitriol (five patients with 0.5 mu g/day for I month and four-patients with 2 mu g/day for 7 days) did not change VDR concentrations. We conclude that the low levels of serum 1,25(OH )(2)D-3 of uremia are not responsible for the decrease in VDR concentration found in these patients. (C) 1998 Prous science. All rights reserved.