Correlation of enhanced cell proliferation with decreased density of vitamin D receptor in parathyroid hyperplasia in chronic dialysis patients

Summary: The decreased density of the vitamin D receptor (VDR) plays an important role in the pathogenesis and progression of parathyroid hyperplasia in renal failure. In chronic dialysis patients, VDR density is less in nodular hyperplasia than in diffuse hyperplasia and the difference of cell proliferation has been also suggested by DNA analysis. to prove a more direct correlation between VDR density and cell proliferation, VDR density and proliferating cell nuclear antigen (PCNA) were detected in situ by immunohistochemistry in serial sections of surgically excised parathyroid glands from 10 chronic dialysis patients. Among 28 excised glands, 20 glands were nodular hyperplasia and eight glands were diffuse hyperplasia. Vitamin D receptor positive cells were much fewer in nodular hyperplasia (13.1 ± 4.8%) than in diffuse hyperplasia (383 ± 5.6%). In contrast, mean PCNA positive cell numbers per one 400 x field were much higher in nodular hyperplasia (2.0± 1.2) than in diffuse hyperplasia (0.1±0.2). These two parameters, simultaneously detected in the same area of the serial sections, showed strong negative correlation (r= -0.719, P <0.0001). Remarkable differences in VDR and PCNA were evident between nodules and the surrounding diffuse hyperplasia in the same section. These data suggest more direct relationship between the decrease of VDR density and parathyroid cell proliferation in chronic renal failure as a pathophysiological mechanism.