INTRODUCTION AND AIMS: Renal ischemia/reperfusion (I/R) injury occurs in patients undergoing renal transplantation and with acute kidney injury (AKI) and it is responsible for the development of chronic fibrotic graft/organ lesions. Heparanase (HPSE), an endoglycosidase that regulate epithelial to mesenchymal transition (EMT) and macrophages polarization, may play a central role in this process. However, its involvement is only partially investigated. METHODS: To assess this research objective,

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... we measured the ability of HPSE and its inhibitor SST0001 to regulate the pro-fibrotic biological network triggered by I/R. This effect was induced in vivo by clamping left renal artery for 30 min in wt C57BL/6J mice. Animals were daily treated with SST0001 (an inhibitor of HPSE) and sacrificed after 8 weeks. HPSE, fibrosis and EMT markers were evaluated by biomolecular and histological methodologies together with the assessment of renal histology and measurement of renal function parameters. RESULTS: After I/R mice showed a significant increase of HPSE and EMT markers (alpha-SMA, vimentin, fibronectin), collagen-I and TGF-beta (p<0.001). The specific inhibition of HPSE, then, minimized the aforementioned effects, mitigated histological lesion and the degree of renal parenchymal fibrosis. Moreover, the inhibition of HPSE protected kidney from functional damage as demonstrated by the assessment of blood urea nitrogen (BUN), plasma creatinine and albuminuria. CONCLUSIONS: These results showed that HPSE is a key regulator of the complex pro-fibrotic network leading to kidney/graft damages following I/R. HPSE inhibitor could therefore provide a new pharmacological approach to minimize and prevent the chronic structural and functional alterations induced by I/R. Future studies should be undertaken to confirm these results in clinical settings. SP060 SYNTHETIC ACTH TREATMENT IN PATIENTS WITH MEMBRANOUS NEPHROPATHY