What is the recommended treatment for secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on dialysis using Cinacalcet (Cinacalcet hydrochloride)?

Treatment of Secondary Hyperparathyroidism in CKD Patients on Dialysis with Cinacalcet

Cinacalcet should not be used for routine treatment of secondary hyperparathyroidism in CKD patients on dialysis but should be limited to patients with elevated PTH levels refractory to standard therapy, with normal or high serum calcium, and in whom surgical parathyroidectomy is contraindicated. 1

Indications and Recommendations

• Cinacalcet is FDA-approved specifically for patients with CKD stage 5D (dialysis) who have secondary hyperparathyroidism, with benefits primarily limited to prevention of surgical parathyroidectomy and avoidance of hypercalcemia 1
• Current evidence does not support the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines suggesting that people with CKD on dialysis and elevated PTH levels should receive calcimimetics to decrease serum PTH levels 1
• Cinacalcet provides small reductions in the risk of surgical parathyroidectomy (RR 0.49 [95% CI, 0.40-0.59]) but has little or no effect on all-cause mortality (RR 0.97 [95% CI, 0.89-1.05]) 1

Dosing Protocol

• The recommended starting oral dose is 30 mg once daily, taken with food or shortly after a meal 2
• Tablets should always be taken whole and never chewed, crushed, or divided 2
• Titration should occur no more frequently than every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily 2
• Target iPTH levels should be 150-300 pg/mL 2
• Serum calcium and phosphorus should be measured within 1 week and iPTH should be measured 1-4 weeks after initiation or dose adjustment 2

Monitoring and Safety

• Once maintenance dose is established, serum calcium should be measured approximately monthly 2
• If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur, calcium-containing phosphate binders and/or vitamin D sterols can be used 2
• If serum calcium falls below 7.5 mg/dL or symptoms of hypocalcemia persist, withhold cinacalcet until serum calcium reaches 8 mg/dL and/or symptoms resolve 2
• The most common adverse effects are gastrointestinal, including nausea (RR 2.05 [95% CI, 1.54-2.75]), vomiting (RR 1.95 [95% CI, 1.74-2.18]), and diarrhea (RR 1.15 [95% CI, 1.02-1.29]) 1
• Cinacalcet significantly increases the risk of hypocalcemia (RR 7.38 [95% CI, 5.43-10.03]) 1

Clinical Efficacy

• Cinacalcet effectively reduces PTH levels, with 65% of patients achieving ≥30% reduction in iPTH from baseline (vs. 13% with conventional therapy) 3
• Treatment reduces the risk of hypercalcemia (RR 0.23 [95% CI, 0.05-0.97]) 1
• Cinacalcet decreases serum PTH (mean difference -281 ng/L [95% CI, -326 to -236]) and calcium concentrations (mean difference -0.22 mmol/L [95% CI, -0.25 to -0.19]) 1
• The drug has comparable efficacy in both hemodialysis and peritoneal dialysis patients 3

Practical Considerations

• On average, treating 1,000 people with CKD stage 5D with cinacalcet for 1 year has no effect on survival, prevents about 3 patients from requiring parathyroidectomy, but leads to approximately 60 cases of hypocalcemia and 150 cases of nausea 1
• Benefits may be limited to preventing parathyroidectomy in the small number of patients for whom surgery is contraindicated due to risks outweighing benefits 1
• Cinacalcet can be used alone or in combination with vitamin D sterols and/or phosphate binders 2, 4
• The comparative effectiveness of cinacalcet versus vitamin D compounds for patient-level outcomes remains uncertain due to lack of head-to-head trial data 1

Common Pitfalls and Caveats

• Routine use of cinacalcet therapy in people with CKD does not appear warranted based on current evidence 1
• Cinacalcet has uncertain effects on cardiovascular mortality (RR 0.67 [95% CI, 0.16-2.87]) 1
• Treatment effects on fracture risk are possible but remain imprecise and of lower quality evidence 1
• Data for cinacalcet therapy are largely limited to adults with CKD stage 5D, with insufficient evidence for other CKD stages 1
• Due to relative absence of trials in peritoneal dialysis patients, treatment estimates for this specific group are less certain 1