Korean J Nephrol.  2007 Jul;26(4):440-447.

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

• Park TJ
• Seo JW
• Pack KM
• Chang JW
• Yang WS
• Kim SB
• Lee SK
• Park SK
• Park JS

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.

Keyword

Calcium-sensing receptor; Genetic polymorphism; End-stage renal disease; Hyperparathyroidism; Dialysates

MeSH Terms

Alkaline Phosphatase
Calcium*
Codon
Dialysis
Dialysis Solutions
Genotype
Hip
Humans
Hyperparathyroidism
Kidney Failure, Chronic
Lymphocytes
Osteogenesis
Parathyroid Glands
Parathyroid Hormone*
Phosphorus
Polymerase Chain Reaction
Polymorphism, Genetic
Prospective Studies
Receptors, Calcium-Sensing*
Renal Dialysis*
Risk Factors
Alkaline Phosphatase
Calcium
Codon
Dialysis Solutions
Parathyroid Hormone
Phosphorus
Receptors, Calcium-Sensing