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 μg/d for 3 months and then uptitrated to 2 µg/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. Long-term 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.

Keywords: hyperparathyroidism; kidney transplantation; proteinuria; vitamin D.

Figure 1.

Study flow chart. Sixty kidney transplant recipients with secondary hyperparathyroidism and stable renal function were assessed for eligibility. Forty-three of the 60 participants were randomly assigned to paricalcitol (n=22) or nonparicalcitol (n=21) therapy.

Figure 2.

iPTH levels significantly decreased at 3 and 6 months of treatment with paricalcitol compared with baseline but did not change appreciably during nonparicalcitol therapy. At 3 and 6 months, PTH levels were significantly lower on paricalcitol than nonparicalcitol therapy. Data are means±SEMs. conc., Concentration.

Figure 3.

Effect of paricalcitol on urinary protein excretion. Proteinuria significantly decreased at 6 months of treatment with paricalcitol compared with baseline but did not change appreciably during nonparicalcitol therapy. Data are means±SEMs.