The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism

Abstract

The objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT.

Figure 1

Flow diagram of the inclusion and exclusion process.

Figure 2

Box plots of intact parathyroid hormone (iPTH) concentrations before and after 12 weeks of cinacalcet treatment of 135 participants (a) Baseline iPTH data (b) iPTH concentration after 12 weeks of cinacalcet treatment (c) Absolute change of iPTH concentration from baseline to 12 weeks (d) Percentage change of iPTH concentration from baseline to 12 weeks. In each box, the top, the middle line, and the bottom represent the 75th percentile, the median, and the 25th percentile, respectively. The whiskers show the maximum and the minimum. The data were compared by Kruskal–Wallis test among three genotypes and by Mann–Whitney test between two genotypes. *p < 0.05 was considered statistically significant.

Figure 3

The percentage of patients that achieved at least 30% reduction of intact parathyroid hormone concentration from baseline and the KDIGO recommended PTH target of two to nine times upper limit for the assay used for dialysis patients (130–585 pg/mL) after 12 weeks of cinacalcet treatment. The data were compared by chi-square test. *p < 0.05 was considered statistically significant.