Beyond minerals and parathyroid hormone: Role of active vitamin D in end-stage renal disease

Secondary hyperparathyroidism is a common complication of end-stage renal disease (ESRD) that is often treated with activated forms of intravenous vitamin D. The natural course and treatment of secondary hyperparathyroidism in hemodialysis patients is punctuated by episodes of hypercalcemia, hyperphosphatemia, and increased calcium-phosphate product, which in previous studies were linked to increased mortality. Historically these episodes have been attributed to vitamin D, leading some authorities to favor decreased vitamin D use. However, the studies that examined the impact of mineral levels and parathyroid hormone (PTH) on survival did not consistently account for vitamin D therapy itself on hemodialysis patient survival. The current review examines in detail two recent large-scale studies of hemodialysis patients: one that demonstrated a survival advantage of paricalcitol over calcitriol and a second that demonstrated a significant survival advantage of any intravenous vitamin D formulation versus none. In both studies, the effects were independent of mineral and PTH levels, suggesting "nontraditional" actions of vitamin D contributed to the observed survival advantage. Several of these nontraditional actions are reviewed with an emphasis on those that might impact hemodialysis outcomes.