Association of activated vitamin D treatment and mortality in chronic kidney disease

Background: Treatment of secondary hyperparathyroidism (SHPT) with activated vitamin D analogues is associated with better survival in patients receiving dialysis. It is unclear whether such a benefit is present in patients with predialysis chronic kidney disease (CKD). Methods: We examined the association of oral calcitriol treatment with mortality and the incidence of dialysis in 520 male US veterans (mean [SD] age, 69.8 [10.3] years; 23.5% black) with CKD stages 3 to 5 and not yet receiving dialysis (mean [SD] estimated glomerular filtration rate, 30.8 [11.3]). Associations were examined by the Kaplan-Meier method and in Poisson regression models with adjustment for age, race, comorbidities, smoking, blood pressure, body mass index, use of phosphate binders, estimated glomerular filtration rate, proteinuria, white blood cell count, percentage of lymphocytes, and levels of parathyroid hormone, calcium, phosphorus, albumin, bicarbonate, and hemoglobin. Results: Two hundred fifty-eight of 520 subjects received treatment with calcitriol, 0.25 to 0.5 μg/d, for a median duration of 2.1 years (range, 0.06-6.0 years). The incidence rate ratios for mortality and combined death and dialysis initiation were significantly lower in treated vs untreated patients (P<.001 for both in the fully adjusted models). Treatment with calcitriol was associated with a trend toward a lower incidence of dialysis. These results were consistent across different subgroups. Conclusions: Treatment with the activated vitamin D analogue calcitriol appears to be associated with significantly greater survival in patients with CKD not yet receiving dialysis. Randomized clinical trials are required to verify the causality of these associations and to examine whether similar associations are seen with different activated vitamin D analogues.