Renal denervation as a therapeutic approach for hypertension: novel implications for an old concept.

Hypertension, heart failure, and chronic kidney disease represent a significant and growing global health issue. Current therapeutic strategies for these conditions are mainly based on lifestyle interventions and pharmacological approaches, but the rates of control of blood pressure and the therapeutic efforts to prevent progression of heart failure, chronic kidney disease, and their sequelae remain unsatisfactory, and additional options are required. The contribution of renal sympathetic nerve activity to the development and progression of these disease states has been convincingly demonstrated in both preclinical and human experiments. Preclinical experiments in models of hypertension, myocardial infarction, heart failure, chronic kidney disease, and diabetic nephropathy have successfully used renal denervation as both an experimental tool and a therapeutic strategy.1–6 In the absence of appropriate drugs to pharmacologically reduce blood pressure in severely hypertensive patients, therapeutic splanchnicectomy and even radical surgical sympathectomy were used since the 1930s. In patients with end stage renal disease (ESRD) and uncontrollable hypertension, an even more radical approach, such as bilateral nephrectomy, is sometimes considered. Surgical renal denervation has been shown to be an effective means of reducing sympathetic outflow to the kidneys, increasing urine output (natriuresis and diuresis), and reducing renin release, without adversely affecting other functions of the kidney, such as glomerular filtration rate and renal blood flow. The human transplant experience has clearly demonstrated that the denervated kidney reliably supports electrolyte and volume homeostasis in free-living humans. On the basis of these findings and in view of the demand for alternative treatment options, targeting the renal sympathetic nerves as a major player in the pathophysiology of hypertension, kidney disease, and heart failure is a very attractive therapeutic approach. ### Role of Renal Sympathetic Nerves in Cardiovascular and Kidney Disease The renal sympathetic nervous system has been identified as a major contributor to the complex pathophysiology of hypertension, states of volume overload (such as heart failure), …