Consult Rounds: Zoledronic Acid and Kidney Diseases

1. Bisphosphonates, in particular zoledronate(ZA), have been associated with renal toxicity manifested as deterioration in renal function and potential renal failure. Biopsy findings have suggested ATN. Pamidronate on the other hand leads to a more glomerular pathology namely collapsing FSGS. 
2.  In clinical trials, the risk for renal function deterioration was significantly increased in patients receiving ZA infusion over 5 minutes compared with those receiving the same dose over 15 minutes. An abstract presented at ASCO found via an FDA AERS,  480 cases of bisphosphonate-associated acute kidney injury in cancer patients. Patients were mostly female 298 (56%), mean age 66 with most common cancer being myeloma. Associated agents included ZA (n=411, 87.5%), pamidronate (n=8, 17%), and alendronate (n=36, 2%). 
3. The American Society ofClinical Oncology 2007 Clinical Practice Guideline Update recommends that pamidronate (90mg over no less than 2h) and zoledronate (4mg over 15min) be employed for patients with normal kidney function. In patients with mild-to-moderate kidney disease (estimated CrCl 30-60cc/min), the dose of zoledronate should be reduced with no change in pamidronate, although the committee suggests that clinicians 'consider reducing the initial dose of pamidronate'. For more severe kidney disease (estimated CrCl <30cc/min), zoledronate is not recommended whereas the infusion time for pamidronate should be increased to 4-6h, again with a consideration for reducing the dose. Serum creatinine should be monitored before each dose of bisphosphonate and the drug withheld in patients who develop an otherwise unexplained increase in serum creatinine concentration. 
4. A case of Fanconi syndrome has also been described in ZA use.