Gene polymorphisms in the vitamin D binding protein might influence the response to cinacalcet in patients receiving dialysis, investigators suggest.

In an observational study, 158 patients (mean age 64 years) on hemodialysis initiated the calcimimetic cinacalcet (starting dose 30 mg/d) for secondary hyperparathyroidism (SHPT). Parathyroid hormone (PTH) levels declined by 30% or more over 12 months in 105 treated patients (66.5%), but 53 patients (33.5%) failed to reach that target with cinacalcet treatment. Responders and non-responders had comparable baseline characteristics, such as age, gender, comorbidities, dialysis vintage, body mass index, laboratory values, cardiovascular risk factors, and use of phosphorus binders and paricalcitol.

Investigators analyzed patients’ DNA for polymorphisms in the vitamin D binding protein (rs4588, rs7041) or vitamin D3 receptor gene (rs7975232, rs1544410, rs2228570, rs731236). No significant differences were found in polymorphisms of the vitamin D3 receptor. However, the T436K variant of the vitamin D binding protein rs4588 polymorphism significantly correlated with lower response to cinacalcet, Pablo Conesa-Zamora, PhD, of Universidad Católica de Murcia in Guadalupe, Spain, and colleagues reported in Nephrology Dialysis Transplantation.

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In multivariate analysis, the rs4588 polymorphism, baseline albumin, 25(OH)D, and ferritin emerged as independent predictors of serum PTH. The T allele appeared to confer resistance to cinacalcet in a dominant manner.

“The association reported here, if validated, may partly explain inter-individual differences in the response to cinacalcet treatment in CKD-related [SHPT] patients and may be helpful for dose adjustment,” Dr Conesa-Zamora’s team concluded.


de Alarcón R, Alburquerque-González B, Fernández-Valera A, et al. Pharmacogenetic role of vitamin D-binding protein and vitamin D receptor polymorphisms in the treatment response of dialysis patients with secondary hyperparathyroidism. Nephrol Dial Transplant. Published December 9, 2021. doi:10.1093/ndt/gfab353