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

Abstract

Background 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. Methods 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/m 2)-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. Results 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). Conclusions DPP-4 inhibitors may decrease the risk of cisplatin-induced AKI in diabetic patients.

Therapeutic Effect of Teneligliptin in Drug-Induced Nephrotoxicity: An In-Vitro Study

“…In various studies, DPP-4 inhibitors have been shown to exert nephroprotective effects independent of their blood sugar-controlling effects and have curative effects on diabetic nephropathy [3,4]. Iwakura et al [9] evaluated diabetic cancer patients using DDP-4 inhibitors and reported that cis-induced AKI developed less frequently in these patients. Although the mechanism of the renoprotective effect of DPP-4 is not fully known, it has been suggested that DPP-4 inhibitors provide endothelial protection by reducing oxidative stress and inflammation in clinical studies performed among patients with chronic kidney disease [10,11].…”

Prostaglandin Transporter and Dipeptidyl Peptidase-4 as New Pharmacological Targets in the Prevention of Acute Kidney Injury in Diabetes: An In Vitro Study

“…It is currently unknown whether DPP-4 renal activation contributes to AKI: whereas several studies showed that DPP-4 inhibitors had neutral effects on the risk of AKI in diabetic patients [ 47 , 48 ], extensive evidence indicates that DPP-4 inhibition results in the protection of the kidneys from various types of renal conditions, including AKI [ 21 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. Among this evidence, two studies specifically point to the preventive effect of DPP-4 inhibitors against the development of AKI in diabetic patients: first, the administration of DPP-4 inhibitors to patients with type 2 diabetes mellitus has been linked to reduced chances of AKI within 120 days, in comparison to both diabetic and non-diabetic control groups [ 49 ]; secondly, in diabetic cancer patients undergoing cisplatin treatment, the incidence of AKI was significantly lower (25% vs. 64%) in those treated with DPP-4 inhibitors [ 55 ]. In this context, our current results agree well with the idea that DPP-4 in proximal tubules may play a relevant role in the pathogenic mechanisms responsible for the development of AKI in septic diabetic patients.…”

Comparative effects of incretin-based therapy on doxorubicin-induced nephrotoxicity in rats: the role of SIRT1/Nrf2/NF-κB/TNF-α signaling pathways

“…Furthermore, these treatments have displayed nephroprotective properties in diabetic patients ( Vaghasiya et al, 2011 ; Muskiet et al, 2014 ; Esaki et al, 2017 ; Yaribeygi et al, 2021 ; Youssef et al, 2021 ). Additionally, their beneficial effects on kidney protection extend beyond diabetic models, as demonstrated by their ability to mitigate cisplatin-induced nephropathy ( Katagiri et al, 2013 ; Iwakura et al, 2020 ) in various experimental contexts. This study aimed to explore the potential protective effects of semaglutide, a GLP-1RA, and alogliptin, a DPP-4 inhibitor, against DOX-induced nephrotoxicity.…”