From the Guidelines
Denosumab can be used in patients with chronic kidney disease stage 5 on dialysis (CKD5D), but its use requires careful consideration of the patient's biochemical abnormalities and bone phenotype, as well as close monitoring for hypocalcemia, as noted in the Kidney Disease: Improving Global Outcomes 2017 clinical practice guideline update 1.
Key Considerations
- Denosumab does not require dose adjustment in renal impairment as it is not cleared by the kidneys.
- The standard dosing regimen for osteoporosis is 60 mg subcutaneously every 6 months, while for prevention of skeletal-related events in malignancy, 120 mg is given every 4 weeks.
- When using denosumab in CKD5D patients, it's essential to monitor and correct calcium levels before and during treatment, as these patients are at higher risk for hypocalcemia.
- Supplementation with calcium (1000-1500 mg daily) and vitamin D (800-1000 IU daily) is typically recommended.
- Patients should be monitored for calcium levels within the first week after initial dose and with each subsequent dose.
Mechanism of Action
- Denosumab works by inhibiting RANKL (receptor activator of nuclear factor kappa-B ligand), thereby decreasing osteoclast formation and bone resorption, which makes it particularly useful in CKD patients who often have high bone turnover.
Clinical Guidelines
- The Kidney Disease: Improving Global Outcomes 2017 clinical practice guideline update suggests that treatment choices for CKD5D patients take into account the magnitude and reversibility of biochemical abnormalities and the progression of CKD, with consideration of a bone biopsy 1.
- The guideline also notes that antiresorptives, such as denosumab, may induce significant hypocalcemia, and their risks must be weighed against the accuracy of the diagnosis of the underlying bone phenotype.
From the FDA Drug Label
Renal Impairment: In a study of 55 patients with varying degrees of renal function, including patients on dialysis, the degree of renal impairment had no effect on the pharmacokinetics of denosumab; thus, dose adjustment for renal impairment is not necessary The use of denosumab in patients with CKD5D (Chronic Kidney Disease stage 5 on dialysis) is possible without the need for dose adjustment, as the degree of renal impairment does not affect the pharmacokinetics of denosumab 2.
From the Research
Denosumab Use in CKD5D
- Denosumab can be used in patients with chronic kidney disease (CKD), but it is associated with an increased risk of hypocalcemia, particularly in those with advanced CKD stages, such as CKD5D 3, 4, 5, 6, 7.
- The incidence of hypocalcemia after denosumab use is higher in patients with lower estimated glomerular filtration rate (eGFR) and those receiving maintenance dialysis, with reported rates of mild and severe hypocalcemia being 24.1% and 14.9%, respectively, in patients with eGFR <15 or receiving maintenance dialysis 7.
- Close monitoring of serum calcium levels and aggressive replacement of calcium and calcitriol are required to avoid the development of hypocalcemia in patients with CKD5D treated with denosumab 3, 4, 5.
Safety and Efficacy
- Denosumab has been shown to improve bone mineral density and reduce bone turnover in CKD patients, but its fracture efficacy and safety in this population are not well established 5.
- The use of denosumab in CKD patients is associated with an increased risk of infection, particularly in those receiving immunosuppressive medications or steroids 6.
- A clinical care pathway focused on the safe provision of denosumab in advanced CKD can reduce the risk of hypocalcemia in patients treated with this medication 4.
Recommendations
- Patients with CKD5D should be carefully selected for denosumab treatment, and their CKD-mineral and bone disorder (CKD-MBD) should be optimized before initiating therapy 5.
- Calcium and vitamin D supplementation, as well as close monitoring of serum calcium levels, are essential for patients with CKD5D treated with denosumab 3, 4, 5.