Vitamin D Therapy in Chronic Kidney Disease

Vitamin D therapy in chronic kidney disease has two separate roles: correcting nutritional deficiency with native vitamin D, and controlling secondary hyperparathyroidism with active vitamin D analogues. Falling 1-alpha hydroxylation lowers calcitriol as eGFR falls, and calcium, phosphate, parathyroid hormone and vitamin D abnormalities interact.

Native vitamin D. Cholecalciferol or ergocalciferol corrects a low 25-hydroxyvitamin D level and may lower parathyroid hormone modestly. Do not assume sufficiency from a sunny climate or skin type, so measure the level.

Active analogues. Alfacalcidol, calcitriol and paricalcitol lower parathyroid hormone but raise calcium and phosphate. They are not used routinely in non-dialysis disease.

Targets. 25-hydroxyvitamin D over 50 nmol/L (20 ng/mL). In dialysis, parathyroid hormone 2 to 9 times the upper limit of the assay. In non-dialysis disease, treat a progressive or persistently raised level after correcting calcium, phosphate and vitamin D.

Stepwise. Correct hyperphosphataemia and hypocalcaemia, replace native vitamin D, then use an active analogue for severe or progressive hyperparathyroidism in eGFR under 30. In dialysis, add a calcimimetic for raised parathyroid hormone with high or normal calcium.

Avoid. Active analogues when calcium is over the upper limit, phosphate is high and uncontrolled, or parathyroid hormone is low.

Special groups.

• Children: higher native doses by age and weight, and monitoring of growth.

• Pregnancy: use cholecalciferol only at usual doses. Specialist advice for active analogues.

• Older adults: take care with hypercalcaemia and falls.

• East Africa: thiazides, calcium supplements, granulomatous disease (including tuberculosis) and enzyme-inducing antiepileptic drugs change calcium and vitamin D needs, so review them.

• Cholecalciferol, deficiency (25-hydroxyvitamin D under 50 nmol/L): 20,000 to 50,000 units once weekly for 8 to 12 weeks, or 2000 to 4000 units daily. Then maintenance 800 to 2000 units daily, adjusted to the level.

• Alfacalcidol: start 0.25 micrograms orally once daily, increased to 0.5 micrograms, in eGFR under 30 with progressive hyperparathyroidism and normal calcium and phosphate.

• Calcitriol: 0.25 micrograms orally once daily, increased to 0.5 micrograms.

• Paricalcitol: oral 1 microgram daily or 2 micrograms three times weekly. Intravenous in dialysis 0.04 to 0.1 micrograms/kg three times weekly, maximum 0.24 micrograms/kg, given at the end of the session.

• Cinacalcet: 30 mg once daily with food, increased every 2 to 4 weeks, maximum 180 mg daily. Etelcalcetide: start 5 mg intravenously at the end of each dialysis session.

Monitoring. Check corrected calcium and phosphate every 2 to 4 weeks for the first 3 months of an active analogue, then every 1 to 3 months. Check parathyroid hormone every 3 months, 25-hydroxyvitamin D every 6 to 12 months, and alkaline phosphatase every 6 months.

Stop rules. Halve or stop the active analogue when corrected calcium is over 2.55 mmol/L, phosphate is persistently high, or parathyroid hormone falls under 2 times the upper limit in dialysis, because of the risk of adynamic bone disease. Stop cinacalcet or etelcalcetide for symptomatic hypocalcaemia or corrected calcium under 2.0 mmol/L.

Referral and escalation. Refer for severe hyperparathyroidism not controlled by medicines (parathyroid hormone persistently over 9 times the upper limit with hypercalcaemia) for parathyroidectomy, bone pain or fractures, and suspected calciphylaxis.

Common errors. Using active analogues without controlling phosphate, giving native vitamin D without measuring the level, and combining calcium, analogue and thiazide without checking calcium.