Low-dose calcitriol prevents the rise in 1,84 iPTH without affecting serum calcium and phosphate in patients with moderate renal failure (prospective placebo-controlled multicentre trial)

Background. Higher doses of calcitriol are effective in lowering markedly elevated 1,84 PTH levels of patients with renal secondary hyperparathyroidism. It has not been established, however, whether prophylactic administration of low doses of calcitriol prevents an increase of 1,84 PTH without causing side-effects, i.e. hypercalcaemia, hypercalciuria, or hyperphosphataemia. Study design. We carried out a placebo-controlled, double-blind prospective multicentre trial over 12 months in 45 patients with mild to moderate renal failure. Criteria for inclusion were S-creatinine 1.4 mg/dl and 1,84 PTH > 6 pmol/l (normal 6). Calcitriol 0.125 mu g/day per os was compared with placebo. The patients received calcium carbonate per os if serum P exceeded 1.7 mmol/l. Results. Baseline 1,84 iPTH concentrations were not significantly different, i.e. 14.0 pmol/l (6.7-63.3) on placebo vs 16.2 (6.85-82.0) on calcitriol. Intention to treat analysis revealed a significant difference of final 1,84 IPTH, i.e. 27.8 (4.2-68.5) on placebo vs 18.2 (4.45-75.5) on calcitriol. On post-hoc analysis the difference was even more pronounced at S-creatinine concentrations above 3 mg/dl. S-calcium, S-phosphate, and urinary excretion of calcium did not change significantly on either placebo or on calcitriol. There were no episodes of hypercalcaemia or hyperphosphataemia. There was no significant difference of final S-creatinine or change in S-creatinine between placebo and calcitriol. One patient on calcitriol and two on placebo progressed to terminal renal failure. Bone alkaline phosphatase as a non-invasive index of bone metabolism was not decreased to subnormal levels. Conclusion. The results document that a therapeutic window exists in patients with moderate renal failure and elevated of 1,84 iPTH, where low-dose calcitriol (0.125 mu g/day) prevents the increase in 1,84 iPTH without causing side-effects. This observation suggests that the parathyroid is more sensitive to calcitriol than intestine and bone.