Causes and Consequences of Increased Sympathetic Activity in Renal Disease

Abstract

Abstract-Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only caused by hypertension. Another characteristic of renal disease is unbalanced nitric oxide (NO) and angiotensin (Ang) activity. Increased SNA in renal disease may be sustained because a state of NO-Ang II unbalance is also present in the hypothalamus. Very few studies have directly compared the efficacy of adrenergic blockade with other renoprotective measures. Third-generation ␤-blockers seem to have more protective effects than traditional ␤-blockers, possibly via stimulation of NO release. Although it has been extensively documented that muscle SNA is increased in chronic renal failure, data on renal SNA and cardiac SNA are not available for these patients before end-stage renal disease. It is also unknown whether additional treatment with third-generation ␤-blockers can delay the progression of renal injury and prevent cardiac injury in chronic renal failure more efficiently than conventional treatment with angiotensin-converting enzyme inhibitors only. Key Words: renal disease Ⅲ antihypertensive agents Ⅲ hypertension Ⅲ diabetic nephropathy Ⅲ sympathetic nervous system I t is well known that irrespective of the primary cause of renal injury, chronic renal disease often leads to renal fibrosis and end-stage renal disease (ESRD). Delaying the onset of renal replacement therapy is of utmost importance, both medically and economically. 1 Many quite different interventions (dietary protein or phosphate restriction, inhibition of the renin-angiotensin system [RAS], endothelin receptor antagonists, aldosterone antagonists, antioxidants, renal denervation, HMG-CoA reductase inhibitors, etc) have been shown to considerably slow this process in experimental models. In fact, if these were all discrete pathways, then combining such interventions would provide additive protective effects that would exceed the loss of function. Clearly, this is not the case, suggesting that parallel extracellular pathways converge on common intracellular signaling molecules, which in turn activate a limited number of transcription factors that turn on excessive matrix synthesis. Recent studies using modulation of intracellular signaling pathways, eg, by gene transfer of Smad 7, 2 or inhibition of transcription factors with antisense technology 3 show marked reduction of fibrosis in robust models such as unilateral ureteral obstruction. Another pathway that is gaining increasing attention is the independent role of proteinuria in causing interstitial inflammation and ultimately fibrosis. 4 Such inflammation causes cytokine release and consequent monocyte influx. Preventing this monocyte influx by anti-monocyte chemoattractant protein (MCP)-1 gene therapy 5 also reduces injury.In the clinical setting, however, the intracellular domain i...

Cardiac Autonomic Dysfunction Is Associated With High-Risk Albumin-to-Creatinine Ratio in Young Adolescents With Type 1 Diabetes in AdDIT (Adolescent Type 1 Diabetes Cardio-Renal Interventional Trial)

“…Animal data support the role of increased sympathetic activity in the pathogenesis of renal disease (30). A recent study of adults with type 2 diabetes found that cardiac autonomic dysfunction was associated with increased albuminuria and lower eGFR at baseline and also predicted subsequent decline in eGFR (31).…”

Leg sympathetic response to noxious skin stimuli is similar in high and low level human spinal cord injury

“…However, RSNA is not always correlated with blood pressure changes in spinal rats (Hong et al, 1994), thus, it is possible that individuals with lower level SCI could have reflex RSNA from the lower thoracic segments without manifesting AD. Many of the deleterious effects of elevated sympathetic activity to the kidneys are known (Joles and Koomans, 2004) but the long term effects in SCI still need to be investigated. Another pathophysiologic process that could affect all levels of SCI is the observed changes in adipose metabolism due to increased bouts of sympathetic activity that results in increased glycerol release and possible contribution to insulin resistance (Karlsson, 1999b).…”

Mechanisms of Disease: Novel Polymorphisms in Coronary Artery Disease

“…Patients with end-stage renal disease are at high risk for cardiovascular events, even when provided optimal renal replacement therapy (Go et al, 2004;Anavekar et al, 2004). It has been suggested that failure to replicate the endocrine functions of the kidney may contribute to this risk, in association with heightened sympathetic tone (Joles & Koomans 2004;Neumann et al, 2004;Wolfe et al, 1999). Renalase, a flavin adenine dinucleotide-dependent amine oxidase that is secreted into the blood by the kidney, metabolizes circulating catecholamines, and is deficient in chronic kidney disease (Xu et al, 2005).…”