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

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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.