Calcium-Sensing Receptor Gene Polymorphism is Associated with the Parathyroid Response to Low Calcium Dialysate in Hemodialysis Patients with Low Parathyroid Hormone Secretion / 대한신장학회지

ABSTRACT

PURPOSE: Low level of parathyroid hormone (PTH) is a risk factor that might cause hip fracture in dialysis patients. Low calcium dialysate (LCD) has been suggested as an approach to increase PTH level. The calcium-sensing receptor (CaSR) polymorphism is known to be associated with the sensitivity to extracellular calcium. METHODS: We prospectively investigated the role of genetic polymorphism of CaSR codon 990 as one cause of the different parathyroid responses to LCD in maintenance hemodialysis (HD) patients. 48 patients, using 3.5 mEq/L calcium dialysate, with intact PTH below 100 pg/ml for the last one year underwent HD sessions on 2.5 mEq/L calcium dialysate for 12 weeks. Serum intact PTH, total calcium, phosphorus, alkaline phosphatase (ALP) and bone-specific ALP (BAP) were measured monthly. The CaSR gene from peripheral lymphocytes was amplified to confirm the genotype by polymerase chain reaction. RESULTS: According to the CaSR genetic polymorphism, subjects were divided into 3 groups, A/A (14.6 %), A/G (45.8%) and G/G (39.6%). Twelve weeks later, intact PTH (48.5+/-25.4 to 89.0+/-49.4 pg/mL, p<0.01), and ALP (78.7+/-25.7 to 87.4+/-27.2 IU/L, p<0.01) increased significantly in G/G group, but not in non-G/G groups. However, BAP significantly increased in both G/G group (24.3+/-11.9 to 29.5+/-10.6 U/L, p<0.01) and in non-G/G groups (21.4+/-4.5 to 26.1+/-9.1 U/L, p<0.01). During the study period, levels of corrected total calcium and phosphorus were not significantly changed. CONCLUSION: The CaSR polymorphism, G/G genotype, strongly influenced the responsiveness of parathyroid gland to LCD, compared with non-G/G genotypes. However, bone formation may occur actively on LCD, irrespective of CaSR genetic polymorphism.