PARTNERS WITH
Pamidronate disodium, Aredia
Bisphosphonates
MECHANISM OF ACTION
Bisphosphonates diminish bone resorption through many different mechanisms including inhibition of osteoclasts activity. They are excreted by the kidney unmetabolized via glomerular filtration or stored in bones. Thus, a reduced glomerular filtration can lead to increased serum level.
MECHANISM OF KIDNEY INJURY
ATN (Acute tubular necrosis), Water/electrolyte disturbances, Glomerular injury, Podocyte Injury
CLINICAL KIDNEY SYNDROME
AKI, Proteinuria/Albuminuria, Nephrotic syndrome, Signs and symptoms related to electrolyte disturbances
CARDIOVASCULAR ADVERSE EFFECTS
Q-Tc prolongation --PMID: 8208655
LYTE ABNORMALITIES
Hypocalcemia, Hypophosphatemia
RISK FACTORS
The renal effect is dose-dependent and infusion time-dependent. Previous treatment with bisphosphonates and multiple cycles of treatments are also risk factors. Advanced age, baseline renal impairment, advanced cancer, multiple myeloma, hypercalcemia, hypertension, diabetes mellitus, dehydration, concomitant use of nephrotoxic drugs are also factors that increases the risk of bisphosphonates related nephrotoxicity.
Patients are more prone to hypocalcemia if they have pre-existing hypovitaminosis D, hypoparathyroidism, secondary hyperparathyroidism, hypomagnesemia, are receiving concurrent treatment with aminoglycoside or interferon alpha, concurrent treatment with loop diuretics and/or have osteoblastic metastases.
MITIGATION STRATEGIES
To prevent nephrotoxicity, serum creatinine and albuminuria should be monitored according to guidelines. Avoiding dehydration and the use of other nephrotoxic drugs is part of the prevention. When possible, oral bisphosphonate should be privileged. The treatment should be held in case of nephrotoxicity and restarted according to guidelines. There exists no standardized treatment. Lastly, the dose and infusion time should be decided according to guidelines and adjusted to creatinine clearance or glomerular filtrate rate. Bisphosphonates should generally be avoided in case of severe kidney disease (when the indication is not a hypercalcemia of malignancy). To prevent hypocalcemia, calcium and vitamin D supplements should be started prior to treatment initiation and other electrolytes abnormalities should be corrected. Serum electrolytes and vitamin D level should be monitored according to guidelines. The treatment should be held in case of hypocalcemia.
SUGGESTIONS
Hold offending drug and rechallenge after AKI/proteinuria resolves, Discontinue offending drug, Corticosteroids and angiotensin-converting enzyme inhibitors have been used for the treatment of bisphosphonates-induced nephrotic syndrome although their efficacy has not been demonstrated.
NOTES/COMMENTS
PHARMACOKINETICS
Molecular Weight
Volume of Distribution
Plasma Protein Binding
Metabolism
Bioavailability
Half-life elimination
Time to peak
Excretion
Dialyzable?
Unknown
REF:
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PATHOLOGY SLIDES:
ENTRY UPDATES:
Anna-Ève Turcotte
United States
Sep 25, 2022