Persistent hyperparathyroidism in renal allograft recipients: Vitamin D receptor, calcium-sensing receptor, and apoptosis

The phenotypic changes in parathyroid cells after successful renal transplantation remain to be elucidated. We compared 10 diffuse and 11 nodular hyperplastic parathyroid glands from five renal allograft recipients with persistent hyperparathyroidism, with five diffuse and 13 nodular hyperplasia from seven uremic patients on hemodialysis, and 13 normal glands. Comparisons included expressions of both vitamin D receptor (VDR) and calcium-sensing receptor (CaSR), proliferative activity (Ki67), and apoptosis (TUNEL). Immunoreactivity was assessed semiquantitatively and expressed as labeling index. The area/cell was also measured to assess cellular hypertrophy. The labeling indexes of VDR (587±71; mean±s.e.m.) and CaSR (45.0±2.8) in recipients' diffuse hyperplasia were significantly higher than those in uremic diffuse hyperplasia (224±44, 29.3±2.3, respectively) (P<0.01, each). However, these expressions remained low in recipients' nodular hyperplasia (42±8, 11.8±1.4, respectively). Ki67 labeling index in recipients' nodular hyperplasia (7±1) was significantly smaller than in uremic patients (24±6, P<0.01). TUNEL labeling index in recipients' diffuse hyperplasia (30±5) was the highest among the groups. The cell volume tended to be smaller in both patterns of hyperplasia in allograft recipients compared with uremic patients. Our results suggest that the phenotypic change in parathyroid cells after renal transplantation depends on the pattern of hyperplasia, where it is normalized only in diffuse hyperplastic glands in which the number of cells also regresses with significant induction of apoptosis.