Risk factors for nephrotoxicity associated with Cisplatin

Abstract

Background: Cisplatin-induced nephrotoxicity occurs in about one-third of patients who receive this chemotherapy drug. In late 2012, the study institution began measuring serum creatinine on day 7 after administration of cisplatin to identify patients with acute renal failure. Objective: To evaluate the extent of nephrotoxicity associated with cisplatin and the influence of risk factors for nephrotoxicity. Methods: This retrospective study involved patients who received a first cycle of cisplatin-based chemotherapy between November 1, 2012, and November 1, 2013. Patients' medical records were reviewed to determine the increase in creatinine level (graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events) and the influence of certain prespecified risk factors, such as age, concomitant medications, initial dose of cisplatin, and related medical conditions. Results: Among the 80 patients evaluated, 14 (17%) experienced no increase in the level of serum creatinine (grade 0), 44 (55%) experienced a grade 1 increase, 19 (24%) a grade 2 increase, and 3 (4%) a grade 3 increase; no patients experienced a grade 4 increase. Patients with the greatest risk of a grade 2 or 3 increase were those treated with hydrochlorothiazide (odds ratio [OR] 9.35, 95% confidence interval [CI] 2.49 to 35.14) or an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 5.02, 95% CI 1.76 to 14.32). After adjustment, only hydrochlorothiazide was associated with an increased risk of nephrotoxicity (OR 5.39, 95% CI 1.04 to 28.07). Among patients taking hydrochlorothiazide, the average incremental increase in serum creatinine was 59.9 μmol/L (95% CI 34.3 to 85.4 μmol/L). Conclusions:Taking hydrochlorothiazide was associated with a significant increase in serum creatinine following cisplatin therapy. On the basis of these results, patients should stop taking hydrochlorothiazide before undergoing cisplatin-based chemotherapy.