Distal calcific uremic arteriolopathy in a hemodialysis patient responds to lowering of Ca x P product and aggressive wound care.

Calcific uremic arteriolopathy (CUA; calciphylaxis), is reported in approximately 4% of patients receiving hemodialysis, and is characterized by skin lesions that may include firm plaques or subcutaneous nodules. The syndrome has been associated with the use of calcium-containing phosphate binders, high serum phosphorus levels, and elevated calcium x phosphorus (Ca x P) product. This report describes a 73-year-old white male with chronic renal failure due to diabetes mellitus and hypertension, who had been on home hemodialysis for 3 years. He developed CUA after an acute elevation in serum phosphorus (8.1 mg/dl) and Ca x P product (84.2), with painful skin lesions that rapidly progressed to become circumferentially located around the entire lower left extremity. The patient declined amputation, opting for a treatment approach that included aggressive management of phosphorus and calcium, more frequent dialysis, and rigorous wound care. All calcium-containing phosphate binders were discontinued. The patient was switched from calcitriol to paricalcitol, a less calcemic form ofvitamin D replacement therapy, from which he was slowly weaned. Dialysis dose and frequency was also increased to 4 hours, 6 times weekly. The patient was given sevelamer hydrochloride (Renagel)--a calcium-free phosphate binder--with meals at an initial dose of 6.4 g/day. After 5 months, the dose was increased to 8 g/day, with additional dietary counseling to restrict phosphorus intake. At this point, serum phosphorus decreased to 4.9 mg/dl and calcium levels had fallen to 8.5 mg/dl, compared to 9.5 - 10.4 mg/dl prior to diagnosis of CUA with an overall decline in the Ca x P product. Significant healing of the lesions was noted at 8 months following diagnosis, with near-total healing by 12 months. Our studies support that lowering of elevated serum phosphorus, calcium, and Ca x P product, together with aggressive wound care may contribute to the successful outcome of patients with CUA.

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 derivative, will have a positive effect on the immune system with minimal adverse effects on calcium homeostasis. Thirty-one hemodialysis patients not administered vitamin D because of low intact parathyroid hormone (PTH) levels were randomized to placebo or 4 microg of paricalcitol intravenously with the hemodialysis session three times weekly for 12 weeks. Effects on in vivo and ex vivo assessments of immune function were evaluated. All patients achieved 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 patients 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, and interferon-gamma from stimulated lymphocytes were not different between the groups. In contrast to clinical immune effects, paricalcitol increased serum 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 than calcitriol in lymphocytes isolated from either dialysis patients or control subjects. Paricalcitol has a tendency toward improving delayed hypersensitivity reactions, but did not have other proimmune effects. However, as expected, paricalcitol had significant effects on calcium homeostasis compared with placebo. Thus, patients with low PTH levels are unlikely to experience the proimmune effects of vitamin D therapy without more profound and potentially adverse oversuppression of PTH.