Can vitamin D be given to patients with chronic kidney disease (CKD)?

Vitamin D Supplementation in Chronic Kidney Disease

Yes, vitamin D can and should be given to patients with chronic kidney disease, with the specific form and dosing strategy dependent on CKD stage, vitamin D status, and parathyroid hormone levels. 1

CKD Stages 1-4 (Pre-Dialysis): Nutritional Vitamin D Supplementation

For patients with CKD stages 3-4, measure serum 25-hydroxyvitamin D levels and supplement with cholecalciferol or ergocalciferol if levels are below 30 ng/mL. 1

Initial Assessment and Treatment

• Measure 25(OH)D at first encounter in patients with elevated PTH above target range for CKD stage 1
• If 25(OH)D is <30 ng/mL (75 nmol/L), initiate ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) supplementation 1
• For established deficiency, ergocalciferol 50,000 IU weekly for 12 weeks, then monthly maintenance is recommended 1, 2
• For prevention in those over 60 years: 800 IU daily; younger adults: 400 IU daily 1

Monitoring During Nutritional Vitamin D Therapy

• Measure serum calcium and phosphorus at least every 3 months 1
• Discontinue all vitamin D if corrected total calcium exceeds 10.2 mg/dL (2.54 mmol/L) 1
• If phosphorus exceeds 4.6 mg/dL, add or increase phosphate binders; discontinue vitamin D if hyperphosphatemia persists 1
• Reassess 25(OH)D levels annually once replete 1

Special Consideration: Nephrotic-Range Proteinuria

Patients with nephrotic-range proteinuria require higher vitamin D doses due to urinary losses of 25(OH)D and vitamin D-binding protein. 1, 2

CKD Stages 3b-4 with Elevated PTH: Activated Vitamin D

When 25(OH)D is >30 ng/mL but PTH remains above target range for CKD stage, initiate activated vitamin D (calcitriol, alfacalcidol, or doxercalciferol). 1

Criteria for Activated Vitamin D Initiation

• Only prescribe when corrected total calcium <9.5 mg/dL (2.37 mmol/L) AND phosphorus <4.6 mg/dL (1.49 mmol/L) 1
• Do not use in patients with rapidly declining kidney function or poor medication compliance 1
• Initial dosing: calcitriol 0.25 mcg daily, alfacalcidol 0.25 mcg daily, or doxercalciferol 2.5 mcg three times weekly 1

Monitoring During Activated Vitamin D Therapy

• Measure calcium and phosphorus monthly for first 3 months, then every 3 months 1
• Measure PTH every 3 months for 6 months, then every 3 months thereafter 1
• Hold therapy if calcium >9.5 mg/dL or phosphorus >4.6 mg/dL until levels normalize, then resume at half dose 1

CKD Stage 5 (Dialysis): Combined Approach

Dialysis patients should receive both nutritional vitamin D supplementation and activated vitamin D or calcimimetics for PTH control when PTH >300 pg/mL. 1, 3

Nutritional Vitamin D in Dialysis

• 97% of hemodialysis patients have suboptimal 25(OH)D levels 4
• Supplement with multivitamins including water-soluble vitamins for those with inadequate dietary intake 1
• Low 25(OH)D levels (<15 ng/mL) are associated with more severe secondary hyperparathyroidism even in dialysis patients 1

Activated Vitamin D or Calcimimetics

• Paricalcitol (oral): Initial dose = baseline iPTH (pg/mL) ÷ 80, given three times weekly 3
• Paricalcitol (IV): Start at 0.04 mcg/kg three times weekly, titrate based on PTH response 5
• Activated vitamin D therapy reduces all-cause mortality (relative risk 0.73) and cardiovascular mortality (relative risk 0.63) in observational studies 6

Post-Transplant Patients

Kidney transplant recipients should be supplemented to achieve 25(OH)D levels ≥30 ng/mL to optimize bone mineral density and reduce fracture risk. 1

• Follow general population recommendations for vitamin D supplementation 1
• For persistent hyperparathyroidism with hypercalcemia, cinacalcet effectively corrects both abnormalities 1

Critical Pitfalls to Avoid

Do Not Confuse Nutritional and Activated Vitamin D

• Nutritional vitamin D (cholecalciferol, ergocalciferol) corrects 25(OH)D deficiency 1
• Activated vitamin D (calcitriol, paricalcitol) suppresses PTH but does not correct nutritional deficiency 1, 2
• Never use activated vitamin D to treat nutritional vitamin D deficiency 2

Avoid Vitamin A and E Supplementation in Dialysis

• Do not routinely supplement vitamin A or E in CKD stage 5 on dialysis due to toxicity risk 1
• If supplementation is necessary, monitor closely for toxicity 1

Monitor for Hypercalcemia and Hyperphosphatemia

• Recent trials (PRIMO, OPERA) showed activated vitamin D increased hypercalcemia risk without cardiac benefit in CKD stages 3-4 1
• Always verify calcium <9.5 mg/dL and phosphorus <4.6 mg/dL before initiating activated vitamin D 1
• The increase in FGF23 with calcitriol analogues warrants caution 7

Recognize Limited Efficacy in Advanced CKD

• In end-stage kidney disease, nutritional vitamin D alone has limited efficacy due to impaired conversion to calcitriol 2
• These patients require activated vitamin D forms for PTH control 2

Account for Drug Interactions

• Strong CYP3A inhibitors (ketoconazole) increase paricalcitol exposure 3
• Cholestyramine and mineral oil reduce intestinal absorption; separate dosing by 1 hour before or 4-6 hours after 3