Endocrine Abstracts

Background: Secondary hyperparathyroidism (SHPT) is an adaptive process that develops in response to declining kidney function, impaired phosphate excretion, and failure to bioactivate vitamin D. The signal transduction via the calcium-sensing receptor (CaSR) is a key determinant of parathyroid gland hyperplasia.

Aims: To examine the polymorphisms rs1801725 (p.Ala986Ser, G>T), rs1042636 (p.Arg990Gly, A>G), rs1801726 (p.Glu1021Gln, G>C) of CaSR gene as a possible cause of the different responses to cinacalcet.

Materials and methods: In study were enrolled 25 patients undego chronic hemodialysis with SHPT (parathyroid hormone (PTH) levels greater than 800 pg/ml). The mean age of patients was 47 (21–77) years old. Patients were genotyped for rs1801725, rs1042636, rs1801726 of CaSR gene by Sanger sequencing. The initial dosage of cinacalcet was 30 mg/day. All patients were also tested for calcium-phosphate metabolism parameters.

Results: The baseline levels of albumin-corrected calcium were significantly lower in patients with polymorphisms rs1801725, rs1042636, rs1801726 of CaSR gene compared to the patients with wild type genotype (P = 0,01). In 3 months cinacalcet treatment patients homozygous and heterozygous for the rs1801725 polymorphism did not demonstrate significant reduction in PTH from baselinecompared to the patients without this polymorphism in the genotype. The same situation was found for rs1801726 polymorphism carriers. The heterozygous patients for the rs1801726 polymorphismshowedsignificant reduction in PTH andcalcium * phosphate product (Ca*P), while patients without this polymorphismshowed reduction in PTH,ionized calcium, albumin-corrected calcium,phosphate and Ca*Pfrom baseline. After 3 months treatment the homozygous and heterozygous patients for the rs1042636 showed significant reduction of PTH levels, while the patients without this polymorphism showed reduction in PTH, ionized calcium, albumin-corrected calcium, phosphate and Ca*P.

Conclusions: This study shows that polymorphisms rs1801725, rs1042636, rs1801726 of CaSR geneinfluence the effectiveness of cinacalcet treatment. The patients without this polymorphism showed a significantly higher sensitivity to cinacalcet compared to the patients who were carriers of CaSR polymorphisms.