Effect of dipeptidyl peptidase-4 inhibitors on cisplatin-induced acute nephrotoxicity in cancer patients with diabetes mellitus: A retrospective study

• Published in: PloS one 2020-02, Vol.15 (2), p.e0229377
• Main Authors: Iwakura, Takamasa, Fukasawa, Hirotaka, Kitamura, Atsushi, Ishibuchi, Kento, Yasuda, Hideo, Furuya, Ryuichi
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Aged; Analysis; Animal models; Antineoplastic agents; Antineoplastic Agents - adverse effects; Biology and Life Sciences; Cancer; Cancer patients; Cancer research; Cancer therapies; Chemotherapy; Cisplatin; Cisplatin - adverse effects; Clinical trials; Cytokines; Diabetes; Diabetes Complications; Diabetes mellitus; Diabetes Mellitus - physiopathology; Diabetics; Dipeptidyl-peptidase IV; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Drug dosages; Epidermal growth factor receptors; Ethics; Female; Glomerular Filtration Rate; Hemoglobin; Humans; Hydration; Inflammation; Inhibitors; Injury prevention; Internal medicine; Ischemia; Kidneys; Male; Medicine; Medicine and Health Sciences; Middle Aged; Neoplasms - drug therapy; Neoplasms - pathology; Nephrology; Oxidative stress; Patients; Peptidase; Prognosis; Retrospective Studies; Risk reduction; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0229377

Cisplatin is a highly effective chemotherapeutic agent. However, acute kidney injury (AKI) limits its subsequent use, resulting in poor cancer prognosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to attenuate cisplatin-induced AKI in animal models, but the effect in human patients remains to be clarified. We hypothesized that DPP-4 inhibitors can prevent cisplatin-induced AKI in diabetic-cancer patients. We retrospectively reviewed all consecutive cancer patients who were treated with a first cycle of cisplatin-containing regimen between January 2011 and October 2019. We analysed data of diabetic-cancer patients treated with high-dose cisplatin (> 50 mg/m2)-containing regimens. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the patients treated with DPP-4 inhibitors and those treated without DPP-4 inhibitors. A total of 455 patients were treated with cisplatin during the period. Of these, 34 patients were eligible for the analysis. The change of eGFR was significantly less in the patients treated with DPP-4 inhibitors, compared to those without DPP-4 inhibitors [the percentages of eGFR decline (mean ± SD) was 23.6 ± 20.3% vs 43.1± 20.1%, respectively; P = 0.010]. Furthermore, the incidence of AKI was significantly less in the patients treated with DPP-4 inhibitors (25% vs 64%, respectively; P = 0.026). DPP-4 inhibitors may decrease the risk of cisplatin-induced AKI in diabetic patients.