Increased Norepinephrine Secretion in Patients with the Nephrotic Syndrome and Normal Glomerular Filtration Rates: Evidence for Primary Sympathetic Activation

Abstract

Considerable controversy exists in regard to the state of arterial circulatory Nephrotic syndrome integrity in patients with the nephrotic syndrome. Increased sympathetic nervous system activity, along with activation of the renin-angiotensin-aldosterone system and the nonosmotic release of vasopressin, is seen in other states of arterial underfilling. Thus, in the present study, sympathetic nervous system activity was assessed by determining plasma norepinephrine secretion and clearance rates using a whole-body steady-state radionuclide tracer method in 6 edematous patients with the nephrotic syndrome of various parenchymal etiologies and 6 normal control subjects in the supine position. Patients were withdrawn from all medications 7 days prior to study. Mean creatinine clearances and serum creatinine concentrations were normal in both the nephrotic syndrome patients and controls (99 ± 13 vs. 112 ± 15 ml/min, p = NS, 1.1 ± 0.1 vs. 0.8 ± 0.0mg/dl, p = 0.03, respectively). However, the nephrotic syndrome patients exhibited significant hypoalbuminemia (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 ± 58 vs. 119 ± 22 pg/ml, p = 0.07). More significantly, the secretion rate of norepinephrine was markedly increased in nephrotic patients (0.30 ± 0.07 vs. 0.13 ± 0.02 ug/m2/min, p < 0.05), whereas the clearance rate of norepinephrine was similar in the two groups (2.60 ± 0.29 vs. 2.26 ± 0.27 1/min, p = NS). Plasma renin activity and plasma aldosterone, arginine vasopressin and atrial natriuretic peptide concentrations were not different in nephrotic syndrome patients compared with controls. We conclude that the sympathetic nervous system is activated in patients with the nephrotic syndrome, as assessed by the increased whole-body norepinephrine secretion rate, prior to a significant fall in glomerular filtration rate or a marked activation of either the renin-angiotensin-aldosterone system or the nonosmotic release of vasopressin. These data support the presence of arterial underfilling in the nephrotic syndrome.