How to replace vitamin D in End-Stage Renal Disease (ESRD)?

From the Guidelines

Vitamin D replacement in patients with end-stage renal disease (ESRD) typically requires active vitamin D analogs, such as calcitriol, paricalcitol, or doxercalciferol, due to the kidneys' inability to convert regular vitamin D to its active form. The recommended approach is to use these analogs, with treatment individualized based on serum calcium, phosphorus, and parathyroid hormone (PTH) levels, with regular monitoring every 1-3 months 1, 2, 3.

Key Considerations

• Start with lower doses and titrate upward as needed to maintain PTH levels within 2-9 times the upper limit of normal while avoiding hypercalcemia and hyperphosphatemia.
• Patients should also receive phosphate binders with meals to control phosphorus levels and may need dietary phosphorus restriction.
• The use of calcitriol or vitamin D analogues should not be routine in patients not receiving dialysis due to the increased risk for hypercalcemia, but they are acceptable first-line options in patients receiving dialysis 1, 2.

Monitoring and Adjustment

• Regular monitoring of serum calcium, phosphorus, and PTH levels is crucial to adjust the treatment regimen as needed.
• Avoid hypercalcemia, as it may be harmful in all GFR categories of CKD, and restrict the use of calcium-based phosphate binders in patients with hyperphosphatemia across the CKD spectrum 3.

Treatment Goals

• The goal is to maintain PTH levels within a target range while avoiding hypercalcemia and hyperphosphatemia, thereby preventing secondary hyperparathyroidism and bone mineral disorders in ESRD patients.
• Treatment should focus on patients with overt hyperphosphatemia, and the use of calcium-based phosphate binders should be restricted in these patients 2, 3.

From the FDA Drug Label

In the diseased kidney, the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently leading to secondary hyperparathyroidism and disturbances in the calcium and phosphorus homeostasis. Paricalcitol is a synthetic, biologically active vitamin D2 analog of calcitriol. Initial Dosage: CKD Stage 5 (2.2, 2.3) Adult Dose (micrograms) = baseline iPTH (pg/mL) divided by 80. Administer dose orally three times a week. To avoid hypercalcemia only treat patients after their baseline serum calcium has been reduced to 9.5 mg/dL or lower (2.2).

Replacement of Vitamin D in End-Stage Renal Disease (ESRD):

• Use paricalcitol, a synthetic vitamin D2 analog, to replace vitamin D in ESRD patients.
• The initial dose for adults with ESRD is calculated as baseline iPTH (pg/mL) divided by 80, administered orally three times a week 4.
• To avoid hypercalcemia, only treat patients after their baseline serum calcium has been reduced to 9.5 mg/dL or lower 5.
• Monitor serum calcium, phosphorus, and iPTH levels during treatment 6.

From the Research

Replacement of Vitamin D in End-Stage Renal Disease (ESRD)

• The replacement of vitamin D in ESRD can be achieved through various forms of vitamin D, including cholecalciferol, ergocalciferol, and calcifediol 7.
• Calcifediol can be considered a more rapid and effective option for correcting vitamin D deficiency and improving secondary hyperparathyroidism in patients with ESRD 7.
• Vitamin D3 (cholecalciferol) supplementation has been shown to increase 25(OH)D and 1,25(OH)2D levels in patients undergoing dialysis for ESRD, without significant changes in PTH levels or hypercalcemia 8.

Comparison of Vitamin D Forms

• Cholecalciferol and ergocalciferol are two common forms of vitamin D used for replacement therapy in ESRD patients 9.
• A randomized clinical trial found that cholecalciferol was more effective than ergocalciferol in raising serum 25(OH)D levels in non-dialysis-dependent CKD patients while active therapy was ongoing 9.
• However, levels of 25(OH)D declined substantially in both arms following cessation of therapy, suggesting the need for maintenance therapy to sustain levels 9.

Extended-Release Calcifediol

• Extended-release calcifediol has been shown to be effective in replenishing 25-OH vitamin D levels and lowering parathyroid hormone levels in patients with stage 3-4 chronic kidney disease and secondary hyperparathyroidism with hypovitaminosis D 10.
• Extended-release calcifediol has a lower risk of hypercalcemia and hyperphosphatemia compared to active vitamin D analogues 10.

Controversies in Vitamin D Replacement

• There is controversy surrounding the use of nutritional vitamin D replacement in CKD and ESRD patients, with some studies suggesting that it may not be effective in lowering PTH levels or improving clinical outcomes 11.
• A meta-analysis found that nutritional vitamin D replacement did not lower PTH levels in predialysis CKD or ESRD patients, and was inferior to activated vitamin D analogs in reducing PTH levels 11.