Vitamin D is a nutrient that helps the body absorb calcium, playing a part in bone health and overall mineral balance. It also has roles in immune function, blood pressure regulation, and cardiovascular health. For individuals with chronic kidney disease (CKD), particularly those on dialysis, managing this vitamin is difficult. The vast majority of dialysis patients experience low levels of Vitamin D, with deficiency or insufficiency reported in 70% to over 90% of this population. Precise medical management is necessary due to the impaired handling of Vitamin D in kidney failure.
Why Kidney Failure Disrupts Vitamin D Metabolism
The body does not use the Vitamin D obtained from sunlight or diet until it has been processed in a two-step activation pathway. The first step occurs in the liver, where the inactive form of Vitamin D, either D2 or D3, is converted into 25-hydroxyvitamin D, also known as calcidiol. This compound is the storage form of the vitamin and is what is typically measured in blood tests to determine a person’s Vitamin D status.
The second activation step must take place in the kidneys. Here, an enzyme called 1-alpha-hydroxylase converts calcidiol into its biologically active form, 1,25-dihydroxyvitamin D, or calcitriol. Calcitriol is the hormone responsible for regulating calcium absorption in the gut and controlling the parathyroid glands. As kidney function declines in CKD and eventually fails, the amount of 1-alpha-hydroxylase enzyme available is severely reduced.
This failure to complete the activation step leads to a deficiency of active calcitriol. Low levels of calcitriol contribute directly to a condition known as secondary hyperparathyroidism (SHPT), where the parathyroid glands overproduce parathyroid hormone (PTH) in an attempt to raise low calcium levels. This uncontrolled PTH production can pull calcium from the bones, causing bone pain and increasing the risk of fractures.
Distinguishing Standard and Active Vitamin D Therapies
Medical treatment for Vitamin D issues in dialysis patients involves standard nutritional supplements and active hormonal therapies. Standard nutritional Vitamin D is typically cholecalciferol (Vitamin D3) or ergocalciferol (Vitamin D2). These supplements are used to replenish the body’s storage levels of calcidiol (25-hydroxyvitamin D), which is often low due to dietary restrictions and poor health in dialysis patients.
Nutritional Vitamin D requires the failing kidneys to perform the last activation step, making it less effective for immediately correcting the active hormone deficiency. They are generally considered safe for use in dialysis patients and may mildly decrease PTH levels.
Active Vitamin D therapies, often referred to as Vitamin D Receptor Activators (VDRAs), are prescribed to bypass the failed kidney activation process. These medications are synthetic versions of the final hormone, calcitriol, or close analogs. Calcitriol (1,25-dihydroxyvitamin D) is the most direct replacement.
Other common VDRAs include paricalcitol and doxercalciferol. These active forms are designed to suppress the production of PTH with a lower risk of increasing calcium and phosphate levels compared to calcitriol. These active forms act directly on the parathyroid glands to suppress PTH overproduction. VDRAs are administered either as oral capsules or, frequently during hemodialysis sessions, directly into the bloodstream intravenously.
Monitoring Calcium, Phosphate, and PTH Levels
The administration of any Vitamin D form, especially the active therapies, requires monitoring to prevent mineral imbalance. Physicians closely track three specific laboratory markers to ensure the safety and effectiveness of the treatment regimen.
Calcium levels must be monitored because active Vitamin D increases calcium absorption from the intestine. Too much calcium in the blood, known as hypercalcemia, can lead to the deposition of calcium in soft tissues, including blood vessels and heart valves. This risk of vascular calcification is a major factor limiting the dosage of active Vitamin D.
Phosphate levels are also carefully tracked, as active Vitamin D can increase the absorption of phosphate. This can result in hyperphosphatemia, which also contributes to soft tissue calcification. Patients often require phosphate binders—medications that block phosphate absorption in the gut—to be taken alongside meals to manage this risk while on Vitamin D therapy.
Parathyroid Hormone (PTH) levels are monitored to gauge the effectiveness of the active Vitamin D treatment against secondary hyperparathyroidism. The goal is to suppress PTH to an appropriate target range. If PTH levels remain too high, it indicates the need for a dosage adjustment, but if they fall too low, it can lead to adynamic bone disease, a condition where bone turnover is suppressed too much.