Effects of renal denervation in a model of chronic kidney disease

Abstract

Chronic kidney disease (CKD) is characterized by progressive damage and irreversible loss of renal function. The main causes of CKD are cardiovascular diseases, mainly arterial hypertension (AH). Despite advances in pharmacological treatments with antihypertensives and surgical techniques, the increasing number of patients with CKD indicates the need for new therapeutic strategies. Clinical and experimental studies have demonstrated that the renal denervation procedure promotes not only renoprotective effects, but also improvement in cardiac and vascular function and glucose metabolism and insulin sensitivity, indicating effects on other target organs through neurohumoral mechanisms. In CKD, several mechanisms lead to cardiac and renal changes, such as fibrosis, proteinuria and activation of the renin-angiotensin-aldosterone system (RAAS) and increased sympathetic drive. The present project intends to study the underlying mechanisms of renal denervation on cardiovascular and renal improvements in CKD. The experimental model of 5/6 nephrectomy (Nx) will be performed in Wistar rats to induce CKD. Animals will undergo renal denervation and / or blockade of RAAS, and the following parameters will be evaluated: blood pressure, heart rate, renal and splanchnic sympathetic nerve activity, renal function markers. Thus, the present project aims to understand the functional and molecular mechanisms involved in CKD progression, associated with AH, contributing to the development and improvement of new treatments.