Treatment Guidelines for Secondary Hyperparathyroidism in CKD
Secondary hyperparathyroidism in CKD should be managed with a stepwise approach starting with phosphate control, followed by vitamin D therapy, calcimimetics, and surgical intervention for refractory cases, with treatment decisions guided by PTH, calcium, and phosphorus levels.
Pathophysiology and Diagnosis
Secondary hyperparathyroidism (SHPT) develops early in chronic kidney disease (CKD) due to:
- Phosphate retention
- Decreased calcium levels
- Reduced 1,25-dihydroxyvitamin D production
- Increased FGF-23 levels
Diagnostic Testing and Monitoring
- Begin monitoring when GFR falls below 60 mL/min/1.73 m² 1
- Essential laboratory tests:
- Serum parathyroid hormone (PTH)
- Calcium and phosphorus
- Vitamin D levels
- Alkaline phosphatase (bone turnover marker) 1
Target PTH Levels by CKD Stage
| CKD Stage | Target PTH Level |
|---|---|
| CKD G3 | <70 pg/mL |
| CKD G4 | <110 pg/mL |
| CKD G5 | <300 pg/mL |
| CKD G5D | 150-600 pg/mL |
Treatment Algorithm
Step 1: Dietary Phosphate Restriction and Phosphate Binders
- Restrict dietary phosphorus to 800-1,000 mg/day when:
- Serum phosphorus >4.6 mg/dL in CKD stages 3-4
- Serum phosphorus >5.5 mg/dL in CKD stage 5
- PTH levels are elevated above target range 2
- Monitor serum phosphorus monthly after initiating dietary restriction 2
- Use phosphate binders to control serum phosphorus levels 1
Step 2: Vitamin D Therapy
- Correct vitamin D deficiency with nutritional vitamin D supplements
- For more advanced SHPT, use active vitamin D analogs (vitamin D sterols) 1
- Active vitamin D therapy helps suppress PTH gene transcription and parathyroid hyperplasia 3
Step 3: Calcimimetics (for Dialysis Patients)
- Cinacalcet is indicated for SHPT in adult CKD patients on dialysis 4
- Starting dose: 30 mg once daily with food 4
- Titrate dose every 2-4 weeks through sequential doses (30,60,90,120,180 mg once daily) 4
- Target iPTH levels: 150-300 pg/mL 4
- Monitor:
- Serum calcium and phosphorus within 1 week of initiation/dose adjustment
- iPTH levels 1-4 weeks after initiation/dose adjustment 4
- Can be used alone or in combination with vitamin D sterols and/or phosphate binders 4
- Not indicated for CKD patients not on dialysis due to increased risk of hypocalcemia 4
Step 4: Surgical Intervention
- Consider parathyroidectomy when:
- PTH levels >800 pg/mL despite maximal medical therapy
- Severe hyperparathyroidism with hypercalcemia precludes medical therapy
- Evidence of bone disease or other end-organ damage 1
- Surgical options:
- Total parathyroidectomy with or without autotransplantation
- Subtotal parathyroidectomy 1
Treatment Based on PTH Levels
| PTH Level | Treatment Approach |
|---|---|
| Mildly elevated | Optimize calcium and vitamin D levels |
| 150-300 pg/mL | Maintain current therapy |
| 300-500 pg/mL | Increase vitamin D sterols, adjust phosphate binders |
| 500-800 pg/mL | Higher doses of vitamin D sterols, consider adding cinacalcet |
| >800 pg/mL | Consider parathyroidectomy if medical therapy fails |
Monitoring and Adjustments
- Monitor serum calcium and phosphorus within 1 week of treatment initiation or dose adjustment 4
- Monitor iPTH 1-4 weeks after treatment initiation or dose adjustment 4
- Once maintenance dose is established:
- Monitor monthly for dialysis patients
- Monitor every 3-6 months initially, then every 6-12 months once stable 1
Management of Hypocalcemia
If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, or if symptoms of hypocalcemia occur:
- Increase calcium-containing phosphate binders
- Increase vitamin D sterols
If serum calcium falls below 7.5 mg/dL or symptoms persist:
- Withhold cinacalcet until calcium reaches ≥8 mg/dL
- Restart at next lowest dose 4
Common Pitfalls and Caveats
- Early intervention is crucial - SHPT begins early in CKD (Stage 2-3) even when serum phosphorus is normal 2
- Avoid hypercalcemia - Can lead to vascular calcification and increased cardiovascular risk 5
- Balance PTH control - Both over-suppression (causing adynamic bone disease) and under-treatment (causing high-turnover bone disease) are harmful 3
- Consider medication interactions - Vitamin D analogs may increase calcium and phosphorus levels, requiring adjustment of other medications 3
- Monitor for vascular calcification - A serious consequence of uncontrolled SHPT and excessive calcium load 5
Early intervention with vitamin D analogs in CKD stages 3-4 can correct PTH levels and potentially prevent renal bone disease and prolong patient survival 3.