Tanja C Saat1, Ingrid van der Pluijm2, Yanto Ridwan3, Sandra van Damme-van den Engel1, Paula M van Heijningen4, Marian C Clahsen-van Groningen5, Hence J M Verhagen6, Jan N M IJzermans1, Jeroen Essers7, Ron W F de Bruin8. 1. Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands. 2. Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands. 3. Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. 4. Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands. 5. Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands. 6. Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands. 7. Department of Vascular Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Molecular Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: j.essers@erasmusmc.nl. 8. Department of Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address: r.w.f.debruin@erasmusmc.nl.
Abstract
OBJECTIVE: Renal ischaemia reperfusion injury (IRI) is inevitable during open repair of pararenal aortic aneurysms. Pre-operative fasting potently increases resistance against IRI. The effect of fasting on IRI was examined in a hypomorphic Fibulin-4 mouse model (Fibulin-4+/R), which is predisposed to develop aortic aneurysms. METHODS: Wild type (WT) and Fibulin-4+/R mice were either fed ad libitum (AL) or fasted for two days before renal IRI induction by temporary clamping of the renal artery and vein of both kidneys. Six hours, 48 h, and seven days post-operatively, serum urea levels, renal histology, and mRNA expression levels of inflammatory and injury genes were determined to assess kidney function and damage. Additionally, matrix metalloproteinase activity in the kidney was assessed six months after IRI. RESULTS: Two days of fasting improved survival the first week after renal IRI in WT mice compared with AL fed mice. Short term AL fed Fibulin-4+/R mice showed improved survival and kidney function compared with AL fed WT mice, which could not be further enhanced by fasting. Both fasted WT and Fibulin-4+/R mice showed improved survival, kidney function and morphology compared with AL fed mice six months after renal IRI. Fibulin-4+/R kidneys of fasted mice showed reduced apoptosis together with increased matrix metalloprotease activity levels compared with AL fed Fibulin-4+/R mice, indicative of increased matrix remodelling. CONCLUSION: Fibulin-4+/R mice are naturally protected against the short-term, but not long-term, consequences of renal IRI. Pre-operative fasting protects against renal IRI and prevents (long-term) deterioration of kidney function and morphology in both WT and Fibulin-4+/R mice. These data suggest that pre-operative fasting may decrease renal damage in patients undergoing open abdominal aneurysm repair.
OBJECTIVE:Renal ischaemia reperfusion injury (IRI) is inevitable during open repair of pararenal aortic aneurysms. Pre-operative fasting potently increases resistance against IRI. The effect of fasting on IRI was examined in a hypomorphic Fibulin-4mouse model (Fibulin-4+/R), which is predisposed to develop aortic aneurysms. METHODS: Wild type (WT) and Fibulin-4+/R mice were either fed ad libitum (AL) or fasted for two days before renal IRI induction by temporary clamping of the renal artery and vein of both kidneys. Six hours, 48 h, and seven days post-operatively, serum urea levels, renal histology, and mRNA expression levels of inflammatory and injury genes were determined to assess kidney function and damage. Additionally, matrix metalloproteinase activity in the kidney was assessed six months after IRI. RESULTS: Two days of fasting improved survival the first week after renal IRI in WT mice compared with AL fed mice. Short term AL fed Fibulin-4+/R mice showed improved survival and kidney function compared with AL fed WT mice, which could not be further enhanced by fasting. Both fasted WT and Fibulin-4+/R mice showed improved survival, kidney function and morphology compared with AL fed mice six months after renal IRI. Fibulin-4+/R kidneys of fasted mice showed reduced apoptosis together with increased matrix metalloprotease activity levels compared with AL fed Fibulin-4+/R mice, indicative of increased matrix remodelling. CONCLUSION:Fibulin-4+/R mice are naturally protected against the short-term, but not long-term, consequences of renal IRI. Pre-operative fasting protects against renal IRI and prevents (long-term) deterioration of kidney function and morphology in both WT and Fibulin-4+/R mice. These data suggest that pre-operative fasting may decrease renal damage in patients undergoing open abdominal aneurysm repair.