How to manage parathyroid hormone (PTH) levels in patients with end-stage renal disease (ESRD) undergoing dialysis?

From the Guidelines

Controlling parathyroid hormone (PTH) in dialysis patients requires a multifaceted approach targeting mineral bone disorder, with the primary goal of reducing morbidity, mortality, and improving quality of life. The recommended target range for PTH in dialysis patients is 2-9 times the upper limit of normal (approximately 150-600 pg/mL) 1.

Key Management Strategies

• First-line management includes correcting hyperphosphatemia using phosphate binders such as calcium-based binders (calcium carbonate 500-1500 mg with meals), sevelamer (800-1600 mg with meals), or lanthanum carbonate (500-1000 mg with meals) 1.
• Vitamin D deficiency should be corrected with cholecalciferol or ergocalciferol supplementation.
• For secondary hyperparathyroidism, active vitamin D analogs like calcitriol (0.25-1 mcg daily or 1-3 mcg thrice weekly intravenously post-dialysis) or paricalcitol (2-5 mcg intravenously thrice weekly) are effective 1.
• If PTH remains elevated despite these measures, calcimimetics such as cinacalcet (starting at 30 mg daily, titrating up to 180 mg daily as needed) or etelcalcetide (5-15 mg intravenously thrice weekly post-dialysis) can be added 1.

Monitoring and Adjustments

• Regular monitoring of calcium, phosphorus, and PTH levels is essential, with adjustments to therapy based on these values.
• In severe, refractory cases, parathyroidectomy may be considered, with total parathyroidectomy with autotransplantation (TPTX + AT) being a viable option 1.

Considerations

• The choice of surgical approach for parathyroidectomy is controversial, with TPTX + AT being the first choice for the treatment of SHPT in many clinical centers 1.
• Recent studies suggest that the hypocalcemia induced by SHPT with TPTX is mostly temporary, and occurs without the appearance of persistent hypocalcemia or adynamic bone diseases 1. The most effective approach to managing PTH levels in patients with end-stage renal disease undergoing dialysis is a comprehensive strategy that incorporates phosphate binders, vitamin D supplementation, active vitamin D analogs, and calcimimetics, with parathyroidectomy reserved for severe, refractory cases.

From the FDA Drug Label

2 DOSAGE AND ADMINISTRATION

2.1 Chronic Kidney Disease Stages 3 and 4 in Adults Administer paricalcitol capsules orally once daily or three times a week [see Clinical Studies (14. 1)]. When dosing three times weekly, do not administer more frequently than every other day. Initial Dose Table 1 Recommended Paricalcitol Capsules Starting Dose Based upon Baseline iPTH Level

• To be administered not more often than every other day Baseline iPTH Level Daily Dose Three Times a Week Dose* Less than or equal to 500 pg/mL 1 mcg 2 mcg More than 500 pg/mL 2 mcg 4 mcg Dose Titration Table 2 Recommended Paricalcitol Capsules Dose Titration Base upon iPTH Level
• To be administered not more often than every other day Dose Adjustment at 2 to 4 Week Intervals iPTH Level Relative to Baseline Paricalcitol Capsule Dose Daily Dosage Three Times a Week Dosage* The same, increased or decreased by less than 30% Increase dose by 1 mcg 2 mcg Decreased by more than or equal to 30% and less than or equal to 60% Maintain dose - - Decreased by more than 60% or iPTH less than 60 pg/mL Decrease dose by 1 mcg 2 mcg

2.2 Chronic Kidney Disease Stage 5 in Adults Initial Dose Administer the dose of paricalcitol capsules orally three times a week, no more frequently than every other day based upon the following formula: Dose (micrograms) = baseline iPTH (pg/mL) divided by 80 Treat patients only after their baseline serum calcium has been adjusted to 9.5 mg/dL or lower to minimize the risk of hypercalcemia [see Clinical Pharmacology (12.2) and Clinical Studies (14.2)]. Dose Titration Individualize the dose of paricalcitol capsules based on iPTH, serum calcium and phosphorus levels. Titrate paricalcitol capsules dose based on the following formula: Dose (micrograms) = most recent iPTH level (pg/mL) divided by 80 If serum calcium is elevated, the dose should be decreased by 2 to 4 micrograms As iPTH approaches the target range, small, individualized dose adjustments may be necessary in order to achieve a stable iPTH.

To manage parathyroid hormone (PTH) levels in patients with end-stage renal disease (ESRD) undergoing dialysis, the following steps can be taken:

• Initial dose: Administer paricalcitol capsules orally three times a week, with a dose based on the formula: Dose (micrograms) = baseline iPTH (pg/mL) divided by 80.
• Dose titration: Individualize the dose based on iPTH, serum calcium, and phosphorus levels. Titrate the dose using the formula: Dose (micrograms) = most recent iPTH level (pg/mL) divided by 80.
• Monitoring: Monitor serum calcium and phosphorus levels closely after initiation of paricalcitol capsules, during dose titration periods, and during co-administration with strong CYP3A inhibitors.
• Dose adjustment: If serum calcium is elevated, decrease the dose by 2 to 4 micrograms. As iPTH approaches the target range, small, individualized dose adjustments may be necessary to achieve a stable iPTH. 2

From the Research

Managing Parathyroid Hormone (PTH) Levels in ESRD Patients Undergoing Dialysis

To manage PTH levels in patients with end-stage renal disease (ESRD) undergoing dialysis, several strategies can be employed:

• Use of phosphate chelators and vitamin D, along with an appropriate calcium concentration in the dialysis bath 3
• Administration of cinacalcet, a calcimimetic agent that reduces parathormone levels 3, 4, 5
• Control of serum calcium and phosphorus levels, which can help reduce serum PTH levels 6
• Use of calcium-based phosphate binders, which may be sufficient to reduce serum PTH levels in mild secondary hyperparathyroidism 6

Cinacalcet Therapy

Cinacalcet has been shown to be effective in reducing PTH levels in ESRD patients:

• In a study published in The New England Journal of Medicine, 43% of patients receiving cinacalcet reached the primary end point of intact parathyroid hormone levels of 250 pg per milliliter or less, compared to 5% of patients receiving placebo 4
• Another study found that 58% of patients receiving cinacalcet-based regimen reached the primary end point of intact parathyroid hormone levels of 31.8 pmol/L or less, compared to 19% of patients receiving conventional therapy 5
• Cinacalcet therapy has also been shown to increase proximal femur bone mineral density and alleviate itching in ESRD patients 5

Monitoring and Management

Regular monitoring of PTH, calcium, and phosphorus levels is crucial in managing ESRD patients:

• A study found that 51.6% of ESRD patients had serum phosphorus levels > 5.5 mg/dl, and 25.4% had hyperparathyroidism (defined as iPTH > 400 pg/ml) 7
• Treatment of hyperphosphatemia should be more aggressive in hemodialysis patients, and PTH levels should be maintained in the desired range of 100-250 pg/ml 7