Acute Kidney Injury and Bisphosphonate Use in Cancer: A Report From the Research on Adverse Drug Events and Reports (RADAR) Project

Abstract

Purpose: To determine whether acute kidney injury (AKI) is identified within the US Food and Drug Administration's Adverse Events and Reporting System (FDA AERS) as an adverse event resulting from bisphosphonate (BP) use in cancer therapy. Methods:A search of the FDA AERS records from January 1998 through June 2009 was performed; search terms were "renal problems" and all drug names for BPs. The search resulted in 2,091 reports. We analyzed for signals of disproportional association by calculating the proportional reporting ratio for zoledronic acid (ZOL) and pamidronate. Literature review of BP-associated renal injury within the cancer setting was conducted.Results: Four hundred eighty cases of BP-associated acute kidney injury (AKI) were identified in patients with cancer. Two hundred ninety-eight patients (56%) were female; mean age was 66 Ϯ 10 years. Multiple myeloma (n ϭ 220, 46%), breast cancer (n ϭ 98, 20%), and prostate cancer (n ϭ 24, 5%) were identified. Agents included ZOL (n ϭ 411, 87.5%), pamidronate (n ϭ 8, 17%), and alendronate (n ϭ 36, 2%). Outcomes included hospitalization (n ϭ 304, 63.3%) and death (n ϭ 68, 14%). The proportional reporting ratio for ZOL was 1.22 (95% CI, 1.13 to 1.32) and for pamidronate was 1.55 (95% CI, 1.25 to 1.65), reflecting a nonsignificant safety signal for both drugs.

Bisphosphonate nephropathy: A case series and review of the literature

“…A repeated analysis in the same database found 481 acute kidney injuries in cancer patients that were attributed to bisphosphonate use. In 411 cases (87.5%), zoledronate was considered the responsible agent 28 . A French database similarly identified 7 patients who developed acute kidney injury (4 de novo and 3 as acute on chronic renal insufficiency) related to zoledronate.…”

“…In 411 cases (87.5%), zoledronate was considered the responsible agent. 28 A French database similarly identified 7 patients who developed acute kidney injury (4 de novo and 3 as acute on chronic renal insufficiency) related to zoledronate. For 6 patients in whom follow‐up was available, 3 were left with permanent (additional) kidney damage or death.…”

Myeloma-related Kidney Disease

“…On the other hand, a study using the U.S. Food and Drug Administration Adverse Event Reporting System and published cases failed to show a safety signal with any of the bisphosphonates. 92 …”

Side Effects of Bone-Targeted Therapies in Advanced Breast Cancer

“…In the kidneys, bisphosphonates diffuse passively into tubular cells dependent only on serum concentration and protein binding. Consequently, an accumulation of bisphosphonates in the tubular cells can occur with induction of apoptotic processes and development of acute kidney injury [12,36,37,38] due to tubular necrosis, which typically results in a gradual increase in serum creatinine over months that is only slowly reversed after drug discontinuation [11,39,40,41]. Of the available bisphosphonates, zoledronic acid has been linked to most of the reported episodes of renal failure [24,42].…”