Low Dose CalcitriolVersusPlacebo in Patients with Predialysis Chronic Renal Failure*

Abstract

The effects of a small dose of calcitriol (less than or equal to 0.50 micrograms/day) on parathyroid and renal function, bone histomorphometry, and aluminum (Al) metabolism were studied in a randomized double blind study of 30 patients with predialysis chronic renal failure. The patients were followed at least monthly for 8 months. Serum Al levels were measured, and transiliac bone biopsies, double labeled with tetracycline, were obtained at both the beginning and end of the 8-month treatment period. Serum calcium and ionized calcium concentrations increased in the treatment group, and the calcitriol dosage had to be reduced in 8 patients at least once because of hypercalcemia. Calcitriol treatment did not significantly influence either serum A1 levels or the presence of stainable Al in bone. Serum PTH, urinary cAMP excretion, and bone resorption indices decreased in the treatment group, indicating suppression of parathyroid hyperfunction. Throughout the study renal function decreased at a similar rate in both groups, suggesting that calcitriol treatment had no depressive effect on renal function. We conclude that a low dose of calcitriol may be used to preserve or even restore bone metabolism in patients with predialysis chronic renal failure if serum calcium is closely followed and hypercalcemia promptly treated.

A Randomized Multicenter Trial of Paricalcitol versus Calcitriol for Secondary Hyperparathyroidism in Stages 3–4 CKD

“…cCa, albumin-corrected calcium; PTH, parathyroid hormone. partly explained by the lower starting doses used in this study (1 mg paricalcitol and 0.25 mg calcitriol) compared with other trials, and the avoidance of prolonged oversuppression of PTH (14)(15)(16). During the 24-week treatment period, the increase in serum calcium and phosphorus as well as the reduction in alkaline phosphatase were similar between the two groups.…”

“…Studies of calcitriol in the late 1980s enrolled few patients and were designed to increase serum calcium and not specifically to suppress PTH. Nevertheless, calcitriol did significantly decrease PTH (20%-30%), and bone histology tended to improve (15,16). In a placebo-controlled trial in stages 3-4 CKD, doxercalciferol significantly suppressed PTH 46% with minimal hypercalcemia (defined as .10.7 mg/dl) and a slight increase in hypercalciuria (20).…”

“…Thus, most patients with CKD require VDRA therapy to control hyperparathyroidism. The available VDRAs (calcitriol and paricalcitol) and the prohormone VDRAs (doxercalciferol and alfacalcidol) suppress PTH in a dose-dependent fashion independent of the CKD stage (14,15,20,21). Studies of calcitriol in the late 1980s enrolled few patients and were designed to increase serum calcium and not specifically to suppress PTH.…”

“…Secondary endpoints were also assessed on an intention-to-treat basis. On the basis of prior published reports, we estimated a 5% rate of hypercalcemia with paricalcitol and a 30% rate with calcitriol (15,16). To have a 90% power to detect a difference at the P=0.05 confidence level, 42 patients per group were needed.…”

“…A small trial of calcitriol using doses of #0.5 mg/d reported that eight of 15 patients with CKD became hypercalcemic at least once during an 8-month treatment period (15).…”