Daniel Olvera-Posada1,2, Shouzhe Lin3,4, Ghaleb Aboalsamh4, Aaron Haig5, Ian Lobb3,4, Jaskirandeep Grewal3,4, Manujendra N Saha3,4, Alp Sener1,3,4. 1. Departments of Surgery, Division of Urology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. 2. Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico. 3. Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada. 4. Matthew Mailing Centre for Translational Transplant Studies, London Health Sciences Centre, London, ON, Canada. 5. Department of Pathology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Abstract
INTRODUCTION: We sought to design a partial nephrectomy (PN) with contralateral total nephrectomy porcine model and assess the underlying mechanisms of ischemia reperfusion injury (IRI) after PN using a novel, clinically approved resection device. METHODS: Domestic male pigs (n=9) underwent left lower pole PN, allocated to either standard (Group 1) or no ischemia PN (Group 2), followed by contralateral nephrectomy. Biochemical studies were performed at baseline, Day 2, and Day 7; after sacrifice, kidneys were processed for histological analysis. Apoptotic markers were measured by Western blot analyses. Urinary biomarkers were measured to assess acute kidney injury. RESULTS: At Day 2 following PN, there was a significant rise in serum creatinine in Group 1 compared to Group 2 (355 vs. 136 mmol/L; p=0.008). Intra-renal tissue oxygen saturation after PN was inversely correlated with postoperative creatinine (rs -0.75; p=0.012) and the grade of acute tubular necrosis (rs -0.70; p=0.036). We observed a rise in expression of pro-apoptotic markers and pro-inflammatory markers in Group 1 following PN compared to Group 2. Histological analysis revealed higher grade of apoptosis in Group 1. CONCLUSIONS: IRI associated with standard PN has a deleterious impact on acute renal function, markers of tissue injury, and histological parameters, compared to off-clamp PN using the ALTRUS device. We identified several intraoperative and postoperative markers that may be used as predictors for functional and histological injury following PN.
INTRODUCTION: We sought to design a partial nephrectomy (PN) with contralateral total nephrectomy porcine model and assess the underlying mechanisms of ischemia reperfusion injury (IRI) after PN using a novel, clinically approved resection device. METHODS: Domestic male pigs (n=9) underwent left lower pole PN, allocated to either standard (Group 1) or no ischemia PN (Group 2), followed by contralateral nephrectomy. Biochemical studies were performed at baseline, Day 2, and Day 7; after sacrifice, kidneys were processed for histological analysis. Apoptotic markers were measured by Western blot analyses. Urinary biomarkers were measured to assess acute kidney injury. RESULTS: At Day 2 following PN, there was a significant rise in serum creatinine in Group 1 compared to Group 2 (355 vs. 136 mmol/L; p=0.008). Intra-renal tissue oxygen saturation after PN was inversely correlated with postoperative creatinine (rs -0.75; p=0.012) and the grade of acute tubular necrosis (rs -0.70; p=0.036). We observed a rise in expression of pro-apoptotic markers and pro-inflammatory markers in Group 1 following PN compared to Group 2. Histological analysis revealed higher grade of apoptosis in Group 1. CONCLUSIONS: IRI associated with standard PN has a deleterious impact on acute renal function, markers of tissue injury, and histological parameters, compared to off-clamp PN using the ALTRUS device. We identified several intraoperative and postoperative markers that may be used as predictors for functional and histological injury following PN.
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