2024 Eastern States Conference

TITLE: Zoledronic Acid Used In The Setting of Hypercalcemia of Malignancy: Evaluation of AKI Risk for Optimization
AUTHORS: Jessie Cerankowski & Mark R. Attilio, PharmD, BCOP 
OBJECTIVE: At the conclusion of my presentation, the participant will be able to describe the relationship between zoledronic acid and acute kidney injury.
SELF ASSESSMENT QUESTION: What dose and infusion time for zoledronic acid has been the standard for hypercalcemia of malignancy?
BACKGROUND: The primary objective is to assess the impact of reduced CrCl on persistent AKI after receiving zoledronic acid for hypercalcemia of malignancy. Secondary objective is to assess correlation vs causation of persistent AKI for optimization of administration.
METHODOLOGY: This was a retrospective, single center, observational study of patients who received a dose of zoledronic acid inpatient for hypercalcemia of malignancy (HCM). Exclusion criteria included patients under the age of 18, pregnant patients, repeat doses of zoledronic acid < 7 days and patients who received pamidronate 7 days prior or up to 30 days after zoledronic acid and those with missing values.  For the primary objective, patients were stratified in groups according to CrCl cutoffs of ≥30 mL/min and < 30 mL/min, and evaluated for persistent AKI, defined as AKI within 48 hours that did not resolve within 1 week of administration by available records. For secondary outcomes, dosing variables and patient and disease characteristics were evaluated for correlation or causation to the original 24-48 hour AKI event and persistent AKI’s day 3-6.  Primary objective was evaluated nominally and secondary outcomes were evaluated via multivariant binary regression model.
RESULTS: Initially 261 cancer patients were screened for inclusion. After final review, 80 patients met exclusion criteria or were missing evaluable data points. The remaining 181 patients consisted of 23 patients with a CrCl < 30 mL/min and 158 patients with a CrCl > 30 mL/min at time of zoledronic acid administration. For the primary outcome, 3 (1.9%) patients vs 1 (4.3%) patient (p=0.455) had sustained AKI’s at day 3-6 in the arms of CrCl > 30 mL/min and CrCl < 30 mL/min respectively. During secondary analysis, none of the evaluable variables, were statistically significant for persistent AKI’s; however, NSAID administration was statistically significant during univariate (p=0.042) and multivariate analysis (p=0.016) in 24-48 hour AKIs.
CONCLUSIONS: Our study failed to identify an increase in persistent AKIs post zoledronic acid administration in patients with AKI or reduced CrCl on admission. Findings suggest in the setting of HCM, dose adjustments and extended infusion time does not play a significant role in reducing the risk of developing an AKI. This is consistent with previous literature. Overall, there may not be a need to adjust zoledronic acid administration for HCM, larger studies would be needed to solidify this finding.