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Zoledronic Acid, Reclast, Zometa



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.


ATN (Acute tubular necrosis), Water/electrolyte disturbances, Glomerular injury, Podocyte Injury


AKI, Proteinuria/Albuminuria, Nephrotic syndrome, Signs and symptoms related to electrolyte disturbances





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 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.


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 bisphosphonates 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.


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.



Molecular Weight

Volume of Distribution

Plasma Protein Binding



Half-life elimination

Time to peak





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Anna-Ève Turcotte

United States

Sep 25, 2022

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