From the Guidelines
Prolia (denosumab) can be used in patients with Chronic Kidney Disease (CKD), but it requires careful monitoring due to the increased risk of severe hypocalcemia and hypophosphatemia, particularly in those with impaired renal function or on hemodialysis 1.
Key Considerations
- Denosumab may be administered to patients with impaired renal function or even those on hemodialysis, but the dose, schedule, and safety have not yet been fully defined 1.
- Hypocalcemia should be corrected before starting denosumab, and serum calcium monitoring is required, with repletion as needed 1.
- The risk of osteonecrosis of the jaw is a concern with denosumab, and patients should have good oral hygiene, a baseline dental evaluation, and avoid invasive dental surgery during therapy 1.
Monitoring and Precautions
- Monitoring of creatinine clearance is not required to guide dosing of denosumab, but it is crucial to assess the risk of hypocalcemia and hypophosphatemia 1.
- Supplemental calcium and vitamin D are recommended to prevent hypocalcemia in patients receiving denosumab, especially in CKD patients 1.
Benefits and Risks
- Denosumab can be beneficial for CKD patients, as it may help manage bone disorders associated with kidney disease, but the benefits must be weighed against the potential risks, particularly the risk of hypocalcemia and hypophosphatemia 1.
- A nephrologist or endocrinologist should be consulted to determine the best course of treatment for individual CKD patients, considering the potential benefits and risks of denosumab 1.
From the FDA Drug Label
WARNING: SEVERE HYPOCALCEMIA IN PATIENTS WITH ADVANCED KIDNEY DISEASE Patients with advanced chronic kidney disease (eGFR < 30 mL/min/1.73 m2), including dialysis-dependent patients, are at greater risk of severe hypocalcemia following Prolia administration. Severe hypocalcemia resulting in hospitalization, life-threatening events and fatal cases have been reported [see Warnings and Precautions (5. 1)]. The presence of chronic kidney disease-mineral bone disorder (CKD-MBD) markedly increases the risk of hypocalcemia in these patients [see Warnings and Precautions (5. 1)]. 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 [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
Prolia (denosumab) can be harmful in patients with Chronic Kidney Disease (CKD), particularly those with advanced disease (eGFR < 30 mL/min/1.73 m2), as it increases the risk of severe hypocalcemia, which can lead to hospitalization, life-threatening events, and fatal cases 2, 2, 2.
- Patients with CKD should be evaluated for the presence of CKD-MBD before initiating Prolia treatment.
- Treatment with Prolia in patients with advanced CKD should be supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD.
From the Research
Prolia (Denosumab) Harm in Patients with Chronic Kidney Disease (CKD)
- Prolia (denosumab) has been associated with hypocalcemia in patients with CKD, particularly those with advanced disease 3, 4, 5, 6, 7.
- A retrospective study found that 6/8 patients with CKD-5 and 2/5 patients with CKD-4 developed severe hypocalcemia after denosumab treatment 3.
- Another study reported a gradual improvement in bone metabolism in osteoporotic hemodialysis patients treated with denosumab, but also noted a few cases of hypocalcemia, particularly after the first and second injections 4.
- A narrative review highlighted the complexity of fracture prevention in CKD and the potential usefulness of denosumab, but also emphasized the need for close monitoring and aggressive replacement of calcium and calcitriol to avoid hypocalcemia 5.
- A quality improvement initiative found that a clinical care pathway focused on optimizing CKD mineral and bone disorder and providing calcium and vitamin D prophylaxis reduced the risk of denosumab-induced hypocalcemia by 37% in patients with advanced CKD 6.
- A case report and literature review suggested that denosumab should be avoided in advanced CKD due to the potential for life-threatening hypocalcemia 7.
Risk Factors for Hypocalcemia
- Lower baseline serum calcium and 25 hydroxyvitamin D levels 5.
- Both low and high bone turnover 5.
- Advanced CKD, particularly those with estimated glomerular filtration rate <45 mL/min/1.73m2, including dialysis 6.