Vitamin D in Patients with Chronic Kidney Disease: Nothing New under the Sun

Vitamin D deficiency—a common occurrence in patients with chronic kidney disease—plays an integral role in the development of secondary hyperparathyroidism, which in turn can lead to bone fractures and disability. The active form of vitamin D has hydroxyl groups at the 1 and 25 positions. Current options for vitamin D replacement in patients with chronic kidney disease include nonhydroxylated vitamin D (ergocalciferol, cholecalciferol), 25-hydroxyvitamin D, and activated forms. The latter include 1,25-hydroxyvitamin D and the 1-hydroxylated prohormone, which is subsequently 25-hydroxylated by the liver. Because 1-hydroxylase activity is impaired in chronic kidney disease, activated vitamin D offers theoretical advantages over vitamin D compounds that are not 1-hydroxylated and has been prescribed to dialysis patients for more than 20 years. Initially 1,25 hydroxyvitamin D (calcitriol) was used, although the use of vitamin D analogues (chemically modified dihydroxylated compounds, such as paricalcitol and doxercalciferol) is increasingly common.

Prevention of clinical and biochemical evidence of bone disease remains the primary indication for vitamin D supplementation, but over time, the goals of therapy have become more ambitious: achieving more physiologic serum levels of phosphate, calcium, and parathyroid hormone (PTH). Lately, researchers have speculated that activated vitamin D might reduce cardiovascular morbidity and mortality in patients undergoing dialysis and, perhaps, those with milder chronic kidney disease. Current clinical practice guidelines recommend using activated vitamin D in patients with chronic kidney disease (1), and 80% of patients undergoing hemodialysis in the United States use injectable forms of activated vitamin D (2). Medicare spent $375 million during 2005 alone for injectable vitamin D treatment in U.S. patients undergoing dialysis (2). Vitamin D compounds are solidly entrenched in the management of …