When is alpha calcidiol (alfacalcidol) used in patients with Chronic Kidney Disease (CKD)?

When to Use Alpha Calcidiol (Alfacalcidol) in CKD

Alfacalcidol should be initiated in CKD stages 3-5 (non-dialysis) when intact PTH progressively rises or remains persistently above 70 pg/mL, after ensuring corrected serum calcium is <9.5 mg/dL and serum phosphorus is <4.6 mg/dL. 1, 2, 3

Primary Indications by CKD Stage

CKD Stage 3 (GFR 30-59 mL/min/1.73 m²)

• Start alfacalcidol when intact PTH exceeds 70 pg/mL with progressive or persistent elevation above the upper normal limit 1, 2
• Earlier initiation (when creatinine clearance >30 mL/min/1.73 m²) may prevent progression to severe bone disease and result in normal bone histology when patients reach end-stage kidney disease 1, 3, 4
• Bone biopsies demonstrate histomorphometric features of hyperparathyroid bone disease even with modest PTH elevations in this stage 4

CKD Stage 4 (GFR 15-29 mL/min/1.73 m²)

• Reserve alfacalcidol for severe and progressive secondary hyperparathyroidism rather than routine use 1
• The 2017 KDIGO guideline revision emphasizes not routinely using vitamin D analogues in CKD G3a-G5 non-dialysis patients, reserving them for severe cases 1

CKD Stage 5 (Dialysis)

• Use alfacalcidol when intact PTH >300 pg/mL with target range of 150-300 pg/mL 3
• For severe hyperparathyroidism (PTH >500-600 pg/mL), treatment is required as moderate to severe bone disease is typical 3

Absolute Prerequisites Before Initiation

You must verify these laboratory values before prescribing alfacalcidol:

• Corrected serum calcium must be <9.5 mg/dL (absolute requirement) 2, 3
• Serum phosphorus must be <4.6 mg/dL 2, 3
• Intact PTH should be >70 pg/mL for stage 3b CKD 2

Address nutritional vitamin D deficiency first:

• Measure 25-hydroxyvitamin D levels before starting alfacalcidol 2, 3
• If 25(OH)D is <30 ng/mL, correct with ergocalciferol or cholecalciferol (800-1,000 IU daily) before or concurrent with alfacalcidol 2, 3
• Alfacalcidol does not raise 25-hydroxyvitamin D levels and should never be used to treat nutritional vitamin D deficiency 3

Dosing Protocol

Initial Dose

• Start alfacalcidol at 0.25 mcg daily by mouth 1, 2
• In controlled trials, doses of 0.25-0.5 mcg/day effectively lowered PTH, improved bone histology, and increased bone mineral density 1
• A large observational study showed mean alfacalcidol dose of 0.28 mcg/day was effective, with 61.8% receiving daily dosing (mean 0.34 mcg) and others receiving intermittent therapy 3 times weekly (mean 0.19 mcg/day) 5

Dose Adjustments

• If PTH falls below target range (35-70 pg/mL for stage 3b), hold alfacalcidol until PTH rises above target, then resume at half the previous dose (0.125 mcg daily or 0.25 mcg every other day) 2
• If serum calcium exceeds 9.5 mg/dL, immediately discontinue alfacalcidol and resume at half dose only after calcium returns to <9.5 mg/dL 2, 3
• The initial dose was maintained in 67.5% of patients, increased in 22%, and decreased in 10.6% in a large cohort study 5

Monitoring Schedule

First 3 months:

• Check serum calcium and phosphorus at least monthly (or every 2 weeks in the first month) 2, 3, 4
• Measure intact PTH every 3 months 2, 4

After 6 months:

• Continue calcium, phosphorus, and PTH monitoring every 3 months 2

For dialysis patients (CKD stage 5):

• Monitor calcium and phosphorus every 1-3 months 1
• Monitor PTH every 3-6 months 1

Evidence Supporting Efficacy

Benefits Demonstrated in Controlled Trials

• Alfacalcidol at 0.25-0.5 mcg daily lowered intact PTH levels in CKD stage 3 patients 1
• Improved histological features of hyperparathyroid bone disease after 8,12, or 24 months of treatment 1
• Increased bone mineral density in treated patients 1
• In a large cohort of CKD 3-5 patients, mean PTH decreased from 27.5 to 23.1 pmol/L, with more pronounced reduction (41.3 to 30.9 pmol/L) in patients with baseline iPTH >20 pmol/l 5

Safety Profile

• With doses ≤0.5 mcg/day, progressive loss of kidney function did not differ from placebo-treated patients 1, 4
• In the large observational study, only 7.7% of patients had at least one serum calcium value above normal range, and side effects attributed to alfacalcidol were very low 5
• Serum calcitriol increased significantly from 20.6 ng/L to 31.1 ng/L, which may provide additional non-calciotropic clinical benefits 5

Important Caveats and Pitfalls

When NOT to Use Alfacalcidol

• Do not use routinely in CKD G3a-G5 non-dialysis patients based on 2017 KDIGO guideline update, which found unfavorable risk-benefit ratio for treating moderate PTH elevations 1
• The PRIMO and OPERA trials showed paricalcitol (a vitamin D analogue) did not reduce left ventricular mass index and caused hypercalcemia in 22.6-43.3% of patients versus 0.9-3.3% with placebo 1
• Never use alfacalcidol to treat nutritional vitamin D deficiency—use ergocalciferol or cholecalciferol instead 2, 3

Risk of Hypercalcemia

• Hypercalcemia can cause transient or long-lasting deterioration of kidney function 1, 4
• Serum calcium >10.2-10.5 mg/dL is an absolute contraindication to starting alfacalcidol 3
• Continued surveillance is essential, and hypercalcemia must be avoided 1

Comparative Efficacy

• A recent 2025 study found calcitriol was more effective than alfacalcidol in suppressing iPTH levels at significantly lower doses over 3 months 6
• Calcitriol significantly reduced iPTH from 12.5 to 10.7 pg/mL (P=.017), while alfacalcidol did not significantly suppress iPTH (13.31 to 12.5 pg/mL, P=.937) 6
• However, alfacalcidol has the advantage of not requiring renal 25-hydroxylation for activation, making it theoretically preferable in advanced CKD 7, 8

Special Considerations for Kidney Transplant Recipients

• In CKD stages 1-5T (transplant), measure 25(OH)D levels and correct vitamin D deficiency using strategies recommended for the general population 1
• In the first 12 months post-transplant with eGFR >30 mL/min/1.73 m² and low bone mineral density, consider treatment with vitamin D, calcitriol/alfacalcidol, or bisphosphonates 1
• In CKD stages 4-5T with known low bone mineral density, manage as for CKD stages 4-5 non-dialysis patients 1

Clinical Decision Algorithm

Step 1: Verify CKD stage and measure baseline labs (calcium, phosphorus, intact PTH, 25(OH)D)

Step 2: Correct nutritional vitamin D deficiency if 25(OH)D <30 ng/mL with ergocalciferol/cholecalciferol

Step 3: Ensure calcium <9.5 mg/dL and phosphorus <4.6 mg/dL before proceeding

Step 4: For CKD stage 3 with PTH >70 pg/mL (progressive/persistent): Start alfacalcidol 0.25 mcg daily

Step 5: For CKD stage 4-5 non-dialysis: Reserve alfacalcidol only for severe and progressive hyperparathyroidism

Step 6: For CKD stage 5 dialysis with PTH >300 pg/mL: Consider alfacalcidol or other vitamin D analogues

Step 7: Monitor calcium and phosphorus monthly for first 3 months, PTH every 3 months

Step 8: Adjust dose based on PTH response and calcium/phosphorus levels per protocol above