What are the considerations for using Prolia (denosumab) in patients with End-Stage Renal Disease (ESRD) on hemodialysis?

From the Guidelines

Prolia (denosumab) can be administered to patients with End-Stage Renal Disease (ESRD) on hemodialysis, but it requires careful monitoring for severe hypocalcemia and hypophosphatemia due to the increased risk in this population. According to the study 1, denosumab may be given to patients with impaired renal function or those on hemodialysis, but the dose, schedule, and safety have not been fully defined. A single study of 55 patients with creatinine clearance <30 mL/min or on hemodialysis evaluated the use of a 60 mg dose of denosumab, highlighting the need for cautious use in this population. Some key considerations for using Prolia in ESRD patients on hemodialysis include:

• Hypocalcemia should be corrected before starting denosumab, and serum calcium monitoring is required for denosumab, with repletion as needed 1.
• Supplemental calcium and vitamin D are recommended to prevent hypocalcemia in patients receiving denosumab 1.
• The risk of osteonecrosis of the jaw is a concern with denosumab, and oral hygiene, baseline dental evaluation for high-risk individuals, and avoidance of invasive dental surgery during therapy are recommended to reduce this risk 1.
• Denosumab is generally well-tolerated, but its long half-life means its effects persist for months, which is important to consider when planning dialysis schedules or if complications arise. Overall, while Prolia can be used in ESRD patients on hemodialysis, careful monitoring and management of potential side effects are crucial to ensure safe and effective treatment.

From the FDA Drug Label

WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease are at greater risk of severe hypocalcemia following Prolia administration. The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia. Prior to initiating Prolia in patients with advanced chronic kidney disease, evaluate for the presence of CKD-MBD. Treatment with Prolia in these patients should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD. Before initiating Prolia in patients with advanced chronic kidney disease, including dialysis patients, evaluate for the presence of chronic kidney disease mineral and bone disorder with intact parathyroid hormone, serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D. No dose adjustment is necessary in patients with renal impairment. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported postmarketing. In clinical studies, patients with advanced chronic kidney disease (i.e., eGFR < 30 mL/min/1. 73 m2), including dialysis-dependent patients, were at greater risk of developing hypocalcemia.

Considerations for using Prolia in patients with End-Stage Renal Disease (ESRD) on hemodialysis:

• Evaluate for the presence of CKD-MBD before initiating Prolia.
• Supervise treatment with Prolia by a healthcare provider with expertise in CKD-MBD diagnosis and management.
• Monitor calcium and mineral levels (phosphorus and magnesium).
• Ensure adequate intake of calcium and vitamin D.
• Consider the benefits and risks to the patient when administering Prolia to patients with advanced chronic kidney disease 2, 2.

From the Research

Considerations for Using Prolia (Denosumab) in Patients with End-Stage Renal Disease (ESRD) on Hemodialysis

• The use of denosumab in patients with ESRD on hemodialysis is uncertain due to a lack of safety and efficacy data in this population 3.
• Denosumab can cause hypocalcemia and hyperparathyroidism in ESRD patients, as it inhibits osteoclast activation and reduces calcium release from bone, leading to increased parathyroid hormone (PTH) levels as a compensatory mechanism 3, 4.
• Studies have reported cases of severe hypocalcemia following denosumab injection in hemodialysis patients, highlighting the need for careful monitoring of serum calcium levels and adjustment of therapy as needed 4, 5.
• Some studies suggest that denosumab can be a valid treatment option for osteoporotic patients with ESRD, as it does not require dose adjustments for different degrees of renal impairment 5, 6.
• However, the safety and efficacy of denosumab in ESRD patients on hemodialysis need to be carefully evaluated, and patients should be closely monitored for hypocalcemia and other potential adverse effects 7.

Key Factors to Consider

• Assessment and optimization of CKD-mineral and bone disorders (CKD-MBD) prior to initiating denosumab 7.
• Close monitoring of serum calcium levels and adjustment of therapy as needed 3, 4, 5.
• Supplementing with calcium and vitamin D to minimize the risk of hypocalcemia 7.
• Choosing the "right patient" for denosumab, taking into account factors such as baseline serum calcium and 25 hydroxyvitamin D levels, and bone turnover markers 7.