Early onset acute tubular necrosis following single infusion of zoledronate

Abstract

SummaryZoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg /dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent.

Drug‐Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database

“…Aliskiren (ROR 6.39) also has several published case reports of AKI, and new labeling was added to its package insert by the FDA in 2012 advising against concomitant use with angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers in patients with diabetes or renal impairment . Other new potential nephrotoxins such as everolimus (ROR 3.61) and zoledronic acid (ROR 2.23) have also been linked to nephrotoxicity in previous studies and reports …”

“…30 Other new potential nephrotoxins such as everolimus (ROR 3.61) and zoledronic acid (ROR 2.23) have also been linked to nephrotoxicity in previous studies and reports. [31][32][33] Although metformin and digoxin were among the new potential nephrotoxins with the highest AKI RORs (10.65 for metformin; 5.77 for digoxin), the literature provides less evidence for a direct association between these drugs and AKI. 34 The association seen here could be due to other risk factors for AKI that commonly affect patients taking these medications, including diabetes, heart failure, or advanced age.…”

Zoledronic Acid-Induced Acute Renal Failure in Multiple Myeloma

“…This nephrotoxicity occurs at variable intervals compared with the start of treatment with bisphosphonates (1-120 days) [5]. It appears to be dose-and infusion duration-dependent (1.5) but may also occur early and even after a single infusion of the drug, and without any risk factors favoring it [13].…”

Acute Tubular Necrosis Caused by Zoledronic Acid Infusion in a Patient With Osteoporosis

“…There has been only one similar report involving a postmenopausal woman developing ATN within 12 days of an initial zoledronate infusion. 13 This 63-year-old woman was also on immunosuppressive medications, including low-dose prednisone, methotrexate, and tofacitinib. These similarities may suggest a potential interaction of immunosuppressive medications and zoledronate in postmenopausal women having underlying rheumatological disorders.…”

“…These similarities may suggest a potential interaction of immunosuppressive medications and zoledronate in postmenopausal women having underlying rheumatological disorders. 13 Studies on rat models have shown that combination of methotrexate and zoledronate increases BMD in patients with inflammatory arthritis. 14 Further studies are needed to determine such interactions.…”