From the Guidelines
Bisphosphonates can cause acute kidney injury (AKI) through several mechanisms, and to prevent this, it is essential to ensure adequate hydration, adjust dosing based on renal function, and extend infusion times, as recommended by the most recent guidelines 1. Intravenous bisphosphonates, particularly zoledronic acid and pamidronate, pose the highest risk of nephrotoxicity. The mechanism of injury involves direct tubular toxicity, with bisphosphonates causing acute tubular necrosis or collapsing focal segmental glomerulosclerosis. Risk factors include high doses, rapid infusion rates, multiple myeloma, and concurrent use of NSAIDs or other nephrotoxic agents. Some key points to consider when using bisphosphonates include:
- Monitoring renal function before each dose, with particular caution in patients with pre-existing kidney disease, dehydration, or those taking other nephrotoxic medications.
- Ensuring adequate hydration before and during administration.
- Adjusting dosing based on renal function.
- Extending infusion times (at least 15-30 minutes for zoledronic acid).
- Providing supportive care with hydration if AKI develops, and considering temporary discontinuation of other nephrotoxic medications. Most cases of bisphosphonate-induced AKI are reversible with prompt intervention, though severe cases may require temporary dialysis support, as noted in the guidelines 1 and other studies 1. It is also important to note that the use of bisphosphonates should be accompanied by calcium and vitamin D supplementation, and that patients should be monitored for osteonecrosis of the jaw (ONJ) and other potential side effects, as recommended by the guidelines 1. Overall, the key to preventing bisphosphonate-induced AKI is careful patient selection, monitoring, and management, as well as adherence to established guidelines and protocols 1.
From the Research
Bisphosphonate-Induced Acute Kidney Injury (AKI)
- Bisphosphonates have been associated with renal complications, including AKI, particularly in patients with malignant bone diseases 2.
- The mechanisms by which bisphosphonates cause renal insufficiency are still unclear, but it is thought that tubular cell injury may play a role 2.
- Pamidronate, a type of bisphosphonate, can rarely cause collapsing focal segmental glomerular sclerosis with nephrotic syndrome and renal insufficiency 2.
- Other types of renal injury associated with bisphosphonates include transient rises in creatinine and acute tubular necrosis causing acute renal failure 2.
- The frequency of these complications appears to follow the potency of different bisphosphonates, with more potent bisphosphonates being associated with a higher risk of renal complications 2.
Risk Factors and Patient Characteristics
- Patients with cancer, particularly those with multiple myeloma, breast cancer, and prostate cancer, are at increased risk of developing AKI associated with bisphosphonate use 3.
- The majority of cases of bisphosphonate-associated AKI occur in patients receiving intravenous zoledronic acid or pamidronate 3.
- Older adults, particularly those over the age of 65, may be at increased risk of developing AKI associated with bisphosphonate use due to age-related declines in renal function 3.
Monitoring and Prevention
- Monitoring of serum creatinine before and after intravenous bisphosphonate dosing or periodically with oral bisphosphonates is advised to detect potential renal complications early 2.
- Clinicians should be aware of the potential for AKI associated with bisphosphonate use and take steps to prevent and manage it, particularly in high-risk patients 3.