The role of sympathetic nervous activity in renal injury and end-stage renal disease

Sympathetic nervous system hyperactivity is observed in patients with renal injury, renovascular hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD). Elevated sympathetic activity is of prognostic relevance in that plasma norepinephrine concentrations predict survival and the incidence of cardiovascular events in patients with ESRD, as well as future renal injury in normotensive healthy subjects with renal function in the normal range. Renal injury, CKD and ESRD are often associated with obesity, and its common sequelae hypertension and diabetes. In fact, hypertension and diabetes mellitus are the main causes of ESRD in western societies and together account for approximately more than 50% of ESRD incidence in the United States and Japan. Obesity also leads to increases in the incidence of cardiovascular diseases. Several clinical and epidemiological studies have clearly documented that heightened sympathetic nervous activity has an important role in the onset and maintenance of obesity and hypertension. Elevated sympathetic nervous activity may actually represent an important mechanism contributing to the onset and maintenance of renal injury at least in part through its concomitant adverse effects on obesity and hypertension. Understanding the contribution of sympathetic nervous hyperactivity to the onset and maintenance of renal injury might aid in the prevention and treatment of renal injury, CKD and ESRD. Very recently, renal sympathetic denervation was shown to be a potentially novel therapeutic strategy in resistant hypertension. In addition, renin-angiotensin system inhibitors are recommended as the initial therapy because of their renal protective effect, especially in hypertensive patients with type 2 diabetes or with proteinuria. The purpose of this review is to provide an overview of our current knowledge on the relationships between sympathetic nerve activity and renal function to further our understanding of the precise roles of sympathetic nerve activity in renal injury, particularly in the context of obesity and hypertension. These insights may be useful to improve prevention and treatment of renal injury in these patients. Hypertension Research (2010) 33, 521-528; doi: 10.1038/hr.2010.35; published online 26 March 2010