The Impact of Renal Denervation on Structural Changes of Diabetic Nephropathy
Fomison-Nurse, Ingrid Catherine

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Fomison-Nurse, I. C. (2019). The Impact of Renal Denervation on Structural Changes of Diabetic Nephropathy (Thesis, Master of Science). University of Otago. Retrieved from http://hdl.handle.net/10523/9742
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http://hdl.handle.net/10523/9742
Abstract:
Chronic bilateral renal denervation has been shown in clinical and experimental studies to reduce systemic blood pressure in resistant hypertension, along with protective effects on the kidney. However, the role of bilateral renal denervation in the setting of diabetic nephropathy has not been investigated. The aim of this study was to explore the role of bilateral renal denervation on structural changes in the kidney, in an animal model of diabetic nephropathy.Transgenic, renin-overexpressing (mRen-2)27 rats were treated with streptozotocin to induce diabetes, resulting in hypertensive, diabetic rats, to allow the aetiology of diabetic nephropathy to occur. After 12 weeks, the rats were sacrificed, and the renal tissue used in a range of molecular techniques to establish changes in molecular markers of renal injury and fibrosis. Denervation was confirmed with analysis of noradrenaline in the renal tissue, which was significantly decreased by denervation in both normoglycaemic and diabetic animals. Diabetic tissue showed higher levels of noradrenaline, signifying an increased level of renal sympathetic nerve activity, which supported the hypothesis that an increase in renal sympathetic nerve activity results in renin-angiotensin system activation, and renal injury. Diabetic, innervated rats showed lower levels of podocin, indicating glomerular injury, and this was restored by denervation to normoglycaemic levels. Collagen I and collagen IV expression were both increased in diabetic, innervated kidney tissue, and this was also reduced by denervation. Angiotensin II type 1 receptor expression was increased in the renal tissue, indicating renin-angiotensin system activation, which would cause further renal damage and deterioration. The study concluded that bilateral renal denervation is a potential method in which to reduce the detrimental effects on the kidney in an animal model of diabetic nephropathy, through the reduction in sympathetic nerve activity, and subsequent decrease in renin-angiotensin system activity.
Date:
2019
Advisor:
Sammut, Ivan
Degree Name:
Master of Science
Degree Discipline:
Department of Pharmacology
Publisher:
University of Otago
Keywords:
Diabetes; Diabetic; nephropathy; denervation; hypertension; ratmodel; fibrosis; renin-angiotensin
Research Type:
Thesis
Languages:
English
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- Pharmacology and Toxicology [84]
- Thesis - Masters [3419]