INCREASED NOREPINEPHRINE SECRETION IN PATIENTS WITH THE NEPHROTIC SYNDROME AND NORMAL GLOMERULAR-FILTRATION RATES - EVIDENCE FOR PRIMARY SYMPATHETIC ACTIVATION

Considerable controversy exists in regard to the state of arterial cir culatory integrity in patients with the nephrotic syndrome. Increased sympathetic nervous system activity, along with activation of the reni n-angiotensin-aldosterone system and the nonosmotic release of vasopre ssin, is seen in other states of arterial underfilling. Thus, in the p resent study, sympathetic nervous system activity was assessed by dete rmining plasma norepinephrine secretion and clearance rates using a wh ole-body steady-state radionuclide tracer method in 6 edematous patien ts with the nephrotic syndrome of various parenchymal etiologies and 6 normal control subjects in the supine position. Patients were withdra wn from all medications 7 days prior to study. Mean creatinine clearan ces and serum creatinine concentrations were normal in both the nephro tic syndrome patients and controls (99 +/- 1 3 vs. 112 +/- 15 ml/min, p = NS, 1.1 +/- 0.1 vs. 0.8 +/- 0.0 mg/dl, p = 0.03, respectively). Ho wever, the nephrotic syndrome patients exhibited significant hypoalbum inemia (2.0 +/- 0.4 vs. 3.8 +/- 0.1 g/dl, p < 0.01). The supine plasma norepinephrine level was elevated in the patients with the nephrotic syndrome as compared with controls (240 +/- 5 8 vs. 119 +/- 22 pg/ml, p = 0.07). More significantly, the secretion rate of norepinephrine wa s markedly increased in nephrotic patients (0.30 +/- 0.07 vs. 0.13 +/- 0.02 mug/m2/min, p < 0.05), whereas the clearance rate of norepinephr ine was similar in the two groups (2.60 +/- 0.29 vs. 2.26 +/- 0.27 l/m in, p = NS). Plasma renin activity and plasma aldosterone, arginine va sopressin and atrial natriuretic peptide concentrations were not diffe rent in nephrotic syndrome patients compared with controls. We conclud e that the sympathetic nervous system is activated in patients with th e nephrotic syndrome, as assessed by the increased whole-body norepine phrine secretion rate, prior to a significant fall in glomerular filtr ation rate or a marked activation of either the renin-angiotensin-aldo sterone system or the nonosmotic release of vasopressin. These data su pport the presence of arterial underfilling in the nephrotic syndrome.