What medications should be started for secondary hyperparathyroidism (Secondary HPT) management?

Medications to Start for Secondary Hyperparathyroidism

Start with phosphate control using dietary restriction (800-1,000 mg/day) and phosphate binders, followed by vitamin D repletion (ergocalciferol 50,000 IU monthly if 25(OH)D <30 ng/mL), then initiate active vitamin D therapy (calcitriol or paricalcitol) only after serum phosphorus falls below 4.6 mg/dL, targeting PTH levels of 150-300 pg/mL for dialysis patients. 1

Step 1: Control Hyperphosphatemia First

This is the critical first step—never skip this. Starting vitamin D therapy with uncontrolled hyperphosphatemia worsens vascular calcification and increases the calcium-phosphate product. 1

• Target serum phosphorus between 3.5-5.5 mg/dL for stage 5 CKD patients 1
• Initiate dietary phosphorus restriction to 800-1,000 mg/day, adjusted to maintain adequate protein intake of 1.0-1.2 g/kg/day for dialysis patients 1
• Start phosphate binders (calcium-based or non-calcium-based) 1
  • Use calcium carbonate 1-2 g three times daily with meals if patient is hypocalcemic—this serves dual purpose as phosphate binder and calcium supplement 1
  • Avoid calcium-based binders if hypercalcemia is present (calcium >9.5 mg/dL) 2
• Monitor serum phosphorus monthly after initiating therapy 1

Step 2: Replete Native Vitamin D

Before starting active vitamin D therapy, ensure adequate 25-hydroxyvitamin D levels. 1

• Supplement with ergocalciferol (vitamin D2) 50,000 IU monthly if 25(OH)D levels are below 30 ng/mL 1
• Recheck 25(OH)D annually once replete 1
• This step is often overlooked but critical—up to 50% of patients may have vitamin D deficiency 3

Step 3: Address Calcium Abnormalities

• If hypocalcemic: Provide supplemental calcium carbonate 1-2 g three times daily with meals 1, 2
• If hypercalcemic: Consider lowering dialysate calcium concentration from standard 2.5 mEq/L to 1.5-2.0 mEq/L temporarily 2
• Monitor calcium levels within 1 week of initiating therapy 1

Step 4: Initiate Active Vitamin D Therapy

Critical timing: Do NOT start active vitamin D until serum phosphorus falls below 4.6 mg/dL. 1, 2

• For hemodialysis patients: Use intermittent intravenous calcitriol or paricalcitol—this is more effective than oral administration in suppressing PTH levels 1
• For non-dialysis CKD patients: Oral calcitriol, doxercalciferol, or paricalcitol can be used 4, 5
  • Paricalcitol effectively suppresses PTH with minimal impact on serum calcium and phosphorus compared to calcitriol 6
  • Calcitriol has a narrower therapeutic window at higher doses due to hypercalcemia and hyperphosphatemia risk 6
• Adjust dosage according to severity of hyperparathyroidism 1, 4

PTH Targets—Critical Pitfall to Avoid

• Target PTH levels of 150-300 pg/mL for stage 5 CKD/dialysis patients—NOT normal range 1, 2
• Never target normal PTH levels (<65 pg/mL) in dialysis patients—this causes adynamic bone disease with increased fracture risk 1

Step 5: Monitoring Protocol

• Measure serum calcium and phosphorus within 1 week of dialysis initiation or therapy changes 1
• Monitor calcium and phosphorus monthly for the first 3 months, then every 3 months after stabilization 1, 4
• Monitor PTH every 3 months 1, 4
• Measure serum iPTH no earlier than 12 hours after dosing with active vitamin D 7
• Discontinue all vitamin D therapy immediately if calcium rises above 10.2 mg/dL 1

Step 6: Add Calcimimetics if Needed

If PTH remains elevated despite optimized vitamin D therapy, add calcimimetics. 1, 4

• Cinacalcet (oral): Starting dose 30 mg once daily for dialysis patients 7
  • Titrate no more frequently than every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily 7
  • Must be taken with food or shortly after a meal 7
  • Contraindicated if serum calcium is below the lower limit of normal range 7
• Alternative calcimimetics: Etelcalcetide, evocalcet, or upacicalcet have similar or superior efficacy 1
• Cinacalcet effectively reduces PTH and improves biochemical control of mineral and bone disorders 8

Step 7: Consider Parathyroidectomy

Reserve surgery for severe refractory cases. 1, 2, 4

• Indications: PTH persistently >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 1, 2, 4
• Reassess after 3-6 months of optimized medical therapy before proceeding to surgery 1
• Parathyroidectomy is associated with lower mortality than calcimimetics in observational data and shows more substantial increase in bone mineral density 1

Common Pitfalls to Avoid

• Never start vitamin D therapy with uncontrolled hyperphosphatemia—this worsens vascular calcification 1
• Never target normal PTH levels in dialysis patients—causes adynamic bone disease 1
• Never give phosphate supplements together with calcium supplements or high-calcium foods—precipitation in intestinal tract reduces absorption 3
• Never ignore alkaline phosphatase—rising levels with elevated PTH suggest progressive bone disease and add predictive value for assessing bone turnover 1