Treatment of Secondary Hyperparathyroidism of Renal Origin
The treatment of secondary hyperparathyroidism in chronic kidney disease follows a stepwise approach: first control hyperphosphatemia with dietary restriction (800-1,000 mg/day) and phosphate binders, then correct hypocalcemia with calcium supplementation (1-2 g three times daily), followed by vitamin D therapy only after phosphorus is controlled (<4.6 mg/dL), with calcimimetics or parathyroidectomy reserved for refractory cases. 1
Initial Medical Management: Control Hyperphosphatemia First
The foundation of treatment begins with phosphorus control, as uncontrolled hyperphosphatemia will worsen vascular calcification if vitamin D is started prematurely. 1
- Target serum phosphorus between 3.5-5.5 mg/dL for stage 5 CKD patients through dietary phosphorus restriction to 800-1,000 mg/day while maintaining adequate protein intake of 1.0-1.2 g/kg/day for dialysis patients. 1
- Initiate phosphate binders (calcium-based or non-calcium based) to achieve target phosphorus levels. 1
- Monitor serum phosphorus monthly after initiating therapy. 1
Address Hypocalcemia Concurrently
- Provide supplemental calcium carbonate 1-2 g three times daily with meals, which serves the dual purpose of phosphate binder and calcium supplement. 1
- Measure calcium levels within 1 week of initiating therapy. 1
Vitamin D Therapy: Only After Phosphorus Control
Critical pitfall to avoid: Do not initiate active vitamin D therapy until serum phosphorus falls below 4.6 mg/dL, as this worsens vascular calcification and increases calcium-phosphate product. 1
- For hemodialysis patients, intermittent intravenous calcitriol or paricalcitol is more effective than oral administration in suppressing PTH levels. 1
- For peritoneal dialysis patients, oral calcitriol (0.5-1.0 μg) or doxercalciferol (2.5-5.0 μg) can be given 2-3 times weekly. 2
- Target PTH levels of 150-300 pg/mL for stage 5 CKD/dialysis patients—not normal range, as targeting normal PTH (<65 pg/mL) causes adynamic bone disease with increased fracture risk. 1
- Adjust vitamin D sterol dosage according to the severity of hyperparathyroidism. 1
Monitoring During Vitamin D Therapy
- Monitor serum calcium and phosphorus every 2 weeks for 1 month after initiation or dose increase, then monthly. 2
- Monitor PTH monthly for at least 3 months, then every 3 months once target levels are achieved. 2
- If serum calcium rises above 10.2 mg/dL, reduce or temporarily discontinue vitamin D therapy. 1
Calcimimetic Therapy for Persistent Hyperparathyroidism
If PTH remains elevated despite optimized vitamin D therapy, add calcimimetics. 1
- Cinacalcet (FDA-approved) starting dose: 30 mg once daily for dialysis patients, titrated every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily to target iPTH of 150-300 pg/mL. 3
- Novel calcimimetics (etelcalcetide, evocalcet, upacicalcet) have similar or superior efficacy to cinacalcet for PTH reduction. 1
- Measure serum calcium and phosphorus within 1 week and iPTH 1-4 weeks after initiation or dose adjustment. 3
- Limitation: Cinacalcet is not indicated for CKD patients not on dialysis due to increased risk of hypocalcemia. 3
Surgical Management: Parathyroidectomy
Indications for Surgery
Parathyroidectomy is indicated when PTH remains persistently >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy after 3-6 months of optimized treatment. 1, 2
Surgical Options and Outcomes
The choice between total parathyroidectomy (TPTX) and total parathyroidectomy with autotransplantation (TPTX+AT) has been clarified by recent meta-analysis:
- TPTX is superior to TPTX+AT with significantly lower recurrence rates (OR 0.20; 95% CI, 0.11-0.38), lower reoperation rates (OR 0.17; 95% CI, 0.06-0.54), and shorter operative time (17.3 minutes less). 4, 1
- While TPTX has higher risk of hypoparathyroidism (OR 2.97; 95% CI, 1.09-8.08), studies have not shown development of permanent hypocalcemia or adynamic bone disease. 4, 1
- Subtotal parathyroidectomy (SPTX) has fallen out of favor due to high recurrence rates and difficulty with cervical reoperation. 4
Important Surgical Consideration
- Total parathyroidectomy is not recommended for patients who may subsequently receive a kidney transplant, as control of serum calcium levels may be problematic. 2
Postoperative Management
Hungry bone syndrome occurs in 20-70% of patients after parathyroidectomy, with calcium typically reaching nadir at 48-72 hours. 5
- Monitor ionized calcium every 4-6 hours for the first 48-72 hours, then twice daily until stable. 1, 2
- Initiate calcium gluconate infusion if calcium falls below normal. 1
- Adjust phosphate binders as needed based on serum phosphorus levels. 1
- Provide oral calcium carbonate and calcitriol when oral intake is possible. 1
Risk Prediction for Hungry Bone Syndrome
- High-risk patients include those with preoperative PTH >1000-2400 pg/mL, alkaline phosphatase >150-300 U/L, age <48 years, dialysis duration ≥5 years, and high gland weight. 5
- The simple NYU 2-point score (ALP >150 U/L + PTH >1000 pg/mL) showed 96.8% accuracy with 100% negative predictive value for identifying high-risk patients. 5