Sympathetic nervous system activation in renal failure. Its contribution to pathogenesis and progression.

慢性肾功能衰竭尤其是终末期肾病患者的心血管发病率和死亡率极高。最近的研究表明，交感神经的激活在这些患者的高血压、肾脏疾病的进展和心血管预后方面起着重要作用。临床显微神经学检查显示，终末期肾病患者交感神经放电增加，可归因于尿毒症相关毒素。然而，移植物功能良好且没有尿毒症症状的肾移植受者仍然表现出交感神经放电增加。最有趣的是，双侧肾切除患者的神经放电频率与无肾脏疾病的正常对照组相当。这些数据表明，病变的肾脏对交感神经系统产生兴奋作用，不依赖于尿毒症的纠正。本研究旨在全面研究慢性肾功能衰竭和终末期肾病患者中枢(显微神经学)和局部(放射性示踪剂稀释法)的交感神经激活模式。将评估中枢作用的交感神经溶解药物利美尼定对肾脏疾病患者交感神经活性的影响。等待肾移植的终末期肾病患者将在移植前后进行研究。一些移植受者在移植前还将接受单侧或双侧肾切除，这将使我们能够进一步探讨病变肾脏在交感神经激活中的作用。这项研究的结果可能被证明对治疗和预防经常与肾脏疾病相关的心血管疾病事件具有重要意义。

Cardiovascular morbidity and mortality is exceedingly high in patients with chronic renal failure and particularly end stage renal disease. Recent studies suggest that sympathetic activation contributes substantially to the development of hypertension, progression of renal disease and cardiovascular prognosis in these patients. Increased sympathetic nerve firing has been demonstrated in end stage renal disease by the use of clinical microneurography, which has been attributed to uremia-related toxins. However, renal transplant recipients with excellent graft function and no signs of uremia still exhibit increased sympathetic nerve firing. Most interestingly, bilateral nephrectomized patients have nerve firing rates comparable to that of normal control subjects without renal disease. These data suggest that the diseased kidneys exert excitatory effects on the sympathetic nervous system independent of correction of uremia. The proposed study aims to comprehensively investigate the pattern of sympathetic activation both centrally (microneurography) and regionally (radiotracer dilution methodology) in patients with chronic renal failure and end stage renal disease . The effect of the centrally acting sympatholytic drug rilmenidine on sympathetic activity in the setting of renal disease will be assessed. Patients with ESRD waitlisted for kidney transplantation will be studied before and after transplantation. Some of the transplant recipients will also have undergone uni- or bilateral nephrectomy before transplantation which will enable us to further explore the role of the diseased kidneys in sympathetic activation. The results of this study may prove to have significant implications for treatment and prevention of cardiovascular morbid events frequently associated with renal disease.