Ante Jakšić, Dragica Bobinac, Vedran Micek, Tanja Ćelić Črnac, Mirna Bobinac, Marin Oštrić, Josip Španjol, Kristina Pilipović
Surgically induced acute kidney injury (AKI) may involve both ischemia-reperfusion and direct mechanical damage to the renal parenchyma, potentially affecting subsequent tissue repair and remodeling. Although bone morphogenetic protein-7 (BMP-7) has shown renoprotective effects in experimental models of acute kidney injury, most studies have evaluated systemic administration in relatively homogeneous injury models. The effects of local BMP-7 delivery in the setting of combined ischemic and surgical parenchymal injury remain insufficiently defined. In this study, a rat model combining transient renal ischemia-reperfusion with a standardized parenchymal incision was used to investigate renal repair following surgical injury. Recombinant human BMP-7 (rhBMP-7) was applied locally to the injured renal parenchyma using Surgicel as a carrier. Serum renal function measures, tubular injury, proliferative activity, fibrosis-associated remodeling, and selected repair- and BMP-associated signaling markers were evaluated at 7 and 28 days after injury. Local Surgicel/rhBMP-7 application was associated with lower serum blood urea nitrogen and creatinine levels at day 7 compared with the suturing-only surgical-injury group. Histopathological tubular injury was observed in both groups, without significant between-group differences. Increased numbers of proliferating cell nuclear antigen (PCNA)-positive tubular epithelial cells were observed in the Surgicel/rhBMP-7 group at both analyzed time points. Compared with the suturing-only group, the Surgicel/rhBMP-7 group showed higher Wnt-4 immunoreactivity at both time points and higher phosphorylated Smad1/5/8 immunoreactivity at day 28, compatible with differences in BMP-associated signaling. Histological analysis demonstrated a reduced collagen-positive area in the Surgicel/rhBMP-7 group, accompanied by a time-dependent pattern of α-SMA expression. In conclusion, local Surgicel/rhBMP-7 delivery was associated with differences in functional, tubular proliferative, repair-associated signaling, and histological remodeling responses following combined renal ischemia-reperfusion and surgical parenchymal injury. These findings support further evaluation of this localized delivery approach in more comprehensively controlled models of surgical kidney injury.