Paricalcitol for Secondary Hyperparathyroidism in Renal Transplantation

Abstract

Secondary hyperparathyroidism contributes to post-transplant CKD mineral and bone disorder. Paricalcitol, a selective vitamin D receptor activator, decreased serum parathyroid hormone levels and proteinuria in patients with secondary hyperparathyroidism. This single-center, prospective, randomized, crossover, open-label study compared the effect of 6-month treatment with paricalcitol (1 mg/d for 3 months and then uptitrated to 2 mg/d if tolerated) or nonparicalcitol therapy on serum parathyroid hormone levels (primary outcome), mineral metabolism, and proteinuria in 43 consenting recipients of renal transplants with secondary hyperparathyroidism. Participants were randomized 1:1 according to a computer-generated sequence. Compared with baseline, median (interquartile range) serum parathyroid hormone levels significantly declined on paricalcitol from 115.6 (94.8-152.0) to 63.3 (52.0-79.7) pg/ml (P,0.001) but not on nonparicalcitol therapy. At 6 months, levels significantly differed between treatments (P,0.001 by analysis of covariance). Serum bone-specific alkaline phosphatase and osteocalcin decreased on paricalcitol therapy only and significantly differed between treatments at 6 months (P,0.001 for all comparisons). At 6 months, urinary deoxypyridinoline-to-creatinine ratio and 24-hour proteinuria level decreased only on paricalcitol (P,0.05). L3 and L4 vertebral mineral bone density, assessed by dual-energy x-ray absorption, significantly improved with paricalcitol at 6 months (P,0.05 for both densities). Paricalcitol was well tolerated. Overall, 6-month paricalcitol supplementation reduced parathyroid hormone levels and proteinuria, attenuated bone remodeling and mineral loss, and reduced eGFR in renal transplant recipients with secondary hyperparathyroidism. Longterm studies are needed to monitor directly measured GFR, ensure that the bone remodeling and mineral effects are sustained, and determine if the reduction in proteinuria improves renal and cardiovascular outcomes.

Mineral and bone disorder after kidney transplantation

“…Another randomized controlled trial of paricalcitol vs no treatment for 6 mo in prevalent KT recipients with transplant duration 517 years also revealed the ability of paricalcitol in lowering PTH. In this study, vertebral BMD as well as proteinuria improved after paricalcitol therapy [81] . The above evidence indicate that oral active vitamin D are beneficial in alleviating persistent hyperparathyroidism and improving bone mass.…”

Bone Disease after Kidney Transplantation

“…In the same study, moderate renal allograft fibrosis was reduced in the paricalcitol group compared with the control group. Another randomized, crossover study has shown that paricalcitol also reduced bone remodeling as reflected by reduction of bALP and osteocalcin together with improvements in lumbar spine BMD (34). Interestingly, there was a reduction in eGFR associated with paricalcitol therapy, but it is not clear whether this reflects changes in creatinine secretion and generation or a direct effect on GFR.…”

Modern approaches to correction mineral and bone disorders in kidney transplant recipients

“…Согласно при-лагаемой к парикальцитолу инструкции, препарат не рекомендован для коррекции посттрансплан-тационного ГПТ. В последние годы опубликовано всего несколько работ, показавших одинаковые эф-фективность и безопасность парикальцитола в про-филактике и лечении ГПТ у реципиентов почечного трансплантата [32][33][34]. Авторы убедительно проде-монстрировали, что парикальцитол (пероральная форма в дозе 1-2 мкг/сут -3-4 мкг/нед.)…”