VANCOUVER, B.C.—Paricalcitol is more effective than ergocalciferol at lowering parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) stages 3 and 4 and who have vitamin D deficiency and secondary hyperparathyroidism, data suggest.
Moreover, the study revealed that the ergocalciferol dosing regimen advocated by Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines is often ineffective at correcting 25-hydroxyvitamin D [25(OH)D] levels.
“We had to modify this regimen by administering ergocalciferol weekly rather than monthly [in cases where KDOQI suggested the latter] in order to achieve improvement in 25(OH)D levels,” said lead investigator Csaba Kovesdy, MD, Associate Professor of Clinical Medicine at the University of Virginia in Charlottesville and Chief of Nephrology at the Salem VA Medical Center in Salem, Va.
He and his team based their conclusions on the results of a randomized controlled trial involving 80 patients with a mean estimated glomerular filtration rate of 31 mL/min/1.73 m2. The researchers assigned patients to receive paricalcitol 1 or 2 ug daily or ergocalciferol 50,000 units weekly or monthly for a total of 16 weeks. The investigators monitored serum PTH, 25(OH)D, calcium, and phosphorus levels every four weeks. The primary outcome was the effectiveness at lowering PTH, defined as the presence of two consecutive PTH levels that were decreased by at least 30% from baseline.
A total of 76 patients completed the study, 36 in the paricalcitol group and 40 in the ergocalciferol group. The primary endpoint was achieved by 53% of paricalcitol-treated patients compared with only 18% of ergocalciferol recipients, Dr. Kovesdy reported at the World Congress of Nephrology. Mean serum PTH levels did not decrease significantly in the ergocalciferol group (175 pg/mL at baseline and 166 pg/mL at 16 weeks), but did decrease significantly in the paricalcitol group, from 164 to 119.
Serum 25(OH)D levels rose significantly in ergocalciferol-treated subjects but not in paricalcitol recipients. The two groups experienced similar incidences of hyperphosphatemia and hypercalcemia. Both treatments were associated with similar clinical adverse events.
In an interview with Renal & Urology News, Dr. Kovesdy noted that KDOQI guidelines recommend that ergocalciferol be used to start treatment of secondary hyperparathyroidism in CKD patients with 25(OH)D deficiency or insufficiency. Head-to-head comparisons between the KDOQI-recommended regimens and paricalcitol have not previously been performed, however.
“Ours is the first study to directly assess the regimen that KDOQI advocates, and as such it addresses practical issues beyond the scientific question posed,” Dr. Kovesdy said. “We also showed that besides suppressing PTH, paricalcitol was also more effective in lowering elevated bone-specific alkaline phosphatase levels, which provides more direct evidence regarding its benefits on bone metabolism.”
In addition, the study revealed that paricalcitol was superior to ergocalciferol even without dose titration, he pointed out. Patients were started on a fixed dose of the medication based on their initial PTH levels and the dose remained unchanged throughout the study.