Drug Discovery in Preclinical Research (Track)


Robert K. Sylvester, Michelle McKay and Samantha Seelig

NDSU Dept 2660, PO Box 6050, Fargo ND, USA 58108-6050


Purpose: To compare incidence of cisplatin-induced nephrotoxicity with and without mannitol pre-hydration

Methods: Patients administered cisplatin (CDDP) chemotherapy were identified by computer inquiry. Data collected included age, sex, neoplastic diagnosis, CDDP cumulative dose, pre-CDDP serum creatinine (SCr), post-CDDP treatment SCr, and administration of mannitol. Data were collected on 100 patients administered mannitol and 100 patients not administered mannitol. Nephrotoxicity was defined as increase in SCr exceeding normal range. Differences in mean cumulative CDDP dose were analyzed by Student’s T-test, incidence of renal toxicity were analyzed by 2-sample z-test.

Results: Patient age and baseline SCr were similar between groups; patients administered mannitol had a higher mean cumulative CDDP dose (279.8 mg/m2 ± 175.3 vs. 203.2 mg/m2 ± 104.2 P<0.006). The incidence of CDDP-induced nephrotoxicity for patients administered pre-treatment mannitol was 16% lower than for patients not administered mannitol (12% vs. 28% P<0.005, respectively).

Conclusion: Mannitol resulted in a statistically significant reduction of CDDP nephrotoxicity. These data dispute the European Society of Clinical Pharmacy Special Interest Group on Cancer Care recommendation that mannitol does not attenuate CDDP-induced nephrotoxicity. Larger randomized prospective trials are needed to more rigorously determine the ability of mannitol pre-hydration to attenuate CDDP-induced nephrotoxicity.