What is the recommended treatment for secondary hyperparathyroidism (Secondary Hyperparathyroidism) associated with chronic kidney disease (CKD) on dialysis using cinacalcet (Cinacalcet)?

Treatment of Secondary Hyperparathyroidism in CKD Patients on Dialysis with Cinacalcet

Cinacalcet should be reserved for CKD stage 5D (dialysis) patients with secondary hyperparathyroidism who have failed standard therapy and are at risk for parathyroidectomy, rather than used routinely for all patients with elevated PTH. 1, 2

FDA-Approved Indication and Limitations

• Cinacalcet is FDA-approved specifically for secondary hyperparathyroidism in adult CKD patients on dialysis (stage 5D), with benefits primarily limited to preventing surgical parathyroidectomy and avoiding hypercalcemia. 2
• Cinacalcet is contraindicated in CKD patients not on dialysis due to increased risk of hypocalcemia. 2
• Treatment initiation is contraindicated if serum calcium is below the lower limit of normal range. 2

When to Initiate Cinacalcet

Do not use cinacalcet routinely for elevated PTH levels. Current evidence does not support the KDIGO guidelines suggesting calcimimetics for PTH levels beyond 2-9 times the upper normal limit. 3, 1

Consider cinacalcet specifically for:

• Patients with elevated PTH refractory to standard therapy (vitamin D sterols and phosphate binders) who have normal or high serum calcium. 3, 1
• Patients at risk for parathyroidectomy in whom surgical risks outweigh benefits due to comorbidities. 3, 4

Dosing and Titration Protocol

• Starting dose: 30 mg once daily, taken with food or shortly after a meal. 2
• Titration schedule: Increase every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily. 2
• Target iPTH: 150-300 pg/mL (though evidence does not support mortality benefit from achieving this target). 2
• Tablets must be swallowed whole, not chewed, crushed, or divided. 2

Monitoring Requirements

Initial monitoring (first 1-4 weeks):

• Measure serum calcium and phosphorus within 1 week of initiation or dose adjustment. 2
• Measure iPTH 1-4 weeks after initiation or dose adjustment (at least 12 hours after dosing). 2

Maintenance monitoring:

• Serum calcium approximately monthly once maintenance dose established. 2
• More frequent calcium monitoring during dose titration. 2

Managing Hypocalcemia

If serum calcium falls to 7.5-8.4 mg/dL or mild symptoms occur:

• Increase calcium-containing phosphate binders and/or vitamin D sterols. 2

If serum calcium falls below 7.5 mg/dL or symptoms persist:

• Withhold cinacalcet until serum calcium reaches ≥8 mg/dL and symptoms resolve. 2
• Reinitiate at the next lowest dose. 2

Expected Clinical Outcomes

Benefits (treating 1,000 patients for 1 year):

• Prevents approximately 3 patients from requiring parathyroidectomy (RR 0.49). 1, 4
• Reduces hypercalcemia risk (RR 0.23). 1
• Decreases serum PTH by mean of 281 ng/L. 1

No mortality benefit:

• Little or no effect on all-cause mortality (RR 0.97). 1, 4
• Uncertain effects on cardiovascular mortality (RR 0.67). 1, 4

Common Adverse Effects

Gastrointestinal effects (usually mild-moderate and transient):

• Nausea: approximately 150 per 1,000 patients (RR 2.05). 1, 4
• Vomiting: RR 1.95. 1
• Diarrhea: RR 1.15. 1

Hypocalcemia (most significant risk):

• Occurs in approximately 60 per 1,000 patients treated for one year (RR 7.38). 1, 4

Combination Therapy

• Cinacalcet can be used alone or combined with vitamin D sterols and/or phosphate binders. 2
• For severe progressive hyperparathyroidism, vitamin D compounds (calcitriol or paricalcitol) can be combined with cinacalcet, though this increases hypercalcemia risk. 4

Critical Pitfalls to Avoid

• Do not use cinacalcet routinely for all dialysis patients with elevated PTH – evidence shows no mortality benefit and significant adverse effects. 3, 1
• Do not prescribe for CKD patients not on dialysis – this is contraindicated due to hypocalcemia risk. 2
• Do not expect survival benefit – treatment is aimed solely at preventing parathyroidectomy and managing mineral metabolism, not improving mortality. 1, 4
• Monitor calcium aggressively – hypocalcemia is the most significant risk and occurs in a substantial proportion of patients. 1, 2

When to Consider Parathyroidectomy Instead

• If PTH remains severely elevated despite maximum medical therapy (cinacalcet 180 mg daily plus vitamin D compounds). 4
• If surgical risks are acceptable relative to benefits. 4