A placebo-controlled trial to evaluate immunomodulatory effects of paricalcitol

Calcitriol has shown a benefit in various small uncontrolled studies of ex vivo immune function. We hypothesized that paricalcitol, a new vitamin D de rivative, will have a positive effect on the immune system with minimal adv erse effects on calcium homeostasis. Thirty-one hemodialysis patients not a dministered vitamin D because of low intact parathyroid hormone (PTH) level s were randomized to placebo or 4 mug of paricalcitol intravenously with th e hemodialysis session three times weekly for 12 weeks. Effects on in vivo and ex vivo assessments of immune function were evaluated. All patients ach ieved the target dose of paricalcitol. Twenty patients were anergic at the start of the study; 4 of 11 patients in the paricalcitol group and 0 of 9 p atients in the placebo group converted to reactive (P = 0.09). The in vivo response to standard hepatitis B booster vaccine and in vitro proliferation and release of interleukin-2 (IL-2), IL-6, tumor necrosis factor-alpha, an d interferon-gamma from stimulated lymphocytes were not different between t he groups. In contrast to clinical immune effects, paricalcitol increased s erum calcium levels and decreased PTH and bone alkaline phosphatase levels (all P < 0.05). However, hypercalcemia was infrequent. In vitro experiments showed that paricalcitol led to greater dose-dependent thymidine uptake th an calcitriol In lymphocytes isolated from either dialysis patients or cont rol subjects. Paricalcitol has a tendency toward improving delayed hypersen sitivity reactions, but did not have other proimmune effects. However, as e xpected, paricalcitol had significant effects on calcium homeostasis compar ed with placebo. Thus, patients with low PTH levels are unlikely to experie nce the proimmune effects of vitamin D therapy without more profound and po tentially adverse oversuppression of PTH. (C) 2001 by the National Kidney F oundation, Inc.