66). Conclusion: Our results suggest that temporary dialysis-requiring AKI was associated with future UGIB and mortality. Strategies for renal protection and close post-discharge follow-up may be warranted to improve patients’ outcomes. KATAGIRI DAISUKE1, HAMASAKI YOSHIFUMI1, DOI KENT1,2, OKAMOTO KOJI1, NEGISHI KOUSUKE1, NANGAKU MASAOMI1, NOIRI EISEI1 1Department of Nephrology and Endocrinology, University Hospital, University of Tokyo; 2Department of Emergency and Critical Selleck PFT�� Care Medicine, University Hospital, University of Tokyo Introduction: Dipeptidyl-Peptidase 4 (DPP-4) inhibitor, which has been developed as a drug for type 2 diabetes, has been reported

renal protection in rodent ischemia-reperfusion injury. However, the mechanism was unclear because DPP-4 cleaves many molecules including Glucagon-like peptide-1 (GLP-1), stromal cell-derived factor-1 (SDF-1), or neuropeptide Y (NPY).The potential anti-apoptotic effect of GLP-1 from gut has been demonstrated in islet cell lines. GLP-1 receptor (GLP-1R) is expressed in many organs including kidney. Therefore, GLP-1 signaling would have potential cross-organ impacts that

PF-6463922 may affect to kidney function, beyond glucose-lowering response. Methods: C57/BL6 mice were given 10 mg/kg of a selective DPP-4 inhibitor alogliptin (AG) once daily from 7 days before to 96 hr after 15 mg/kg of Cisplatin (CP) injection. DPP-4 activity and its substrates were measured using an enzyme immunoassay (EIA). We demonstrated that no other molecules can be degraded by DPP-4, but GLP-1 had an important role in renal protection by administering a GLP-1R agonist. The GLP-1R knockdown efficacy in the kidney with in vivo siRNA was confirmed using RT-PCR and Western blot. Results: Injection of CP increased BUN and serum creatinine, and caused a remarkable renal pathological injury. AG treatment significantly reduced renal injury induced by CP, though it did not affect blood glucose,

body weight, and blood pressure. The mRNA expression ratios of pro-apoptotic/anti-apoptotic in the AG treated mice were significantly lower than those of the untreated ones. In contrast to SDF-1 and NPY, AG treatment Glutamate dehydrogenase maintained GLP-1 levels at a significantly higher level in AG-treated group. Localization of GLP-1R in proximal tubular cells was demonstrated by immunohistochemistry. Ex-4, GLP-1R agonist, also attenuated CP-induced AKI. Furthermore, to demonstrate that GLP-1R-mediated pathway contributes to renal protection by AG, we conducted an experiment using in vivo siRNA against GLP-1R. Suppressing GLP-1R cancelled renal protective effect of AG. Conclusion: These results support the hypothesis that AG attenuates CP-induced AKI by increasing GLP-1 levels. Anti-apoptotic effects were considered as a possible mechanism of action. This gut-kidney axis could be anticipated as a new drug target in AKI.