Plasma concentration and renal effect of human atrial natriuretic peptide in nephrotic syndrome

To elucidate the pathophysiological role of atrial natriuretic peptide (ANP) in nephrotic syndrome, the plasma level of ANP and renal response to exogenous human alpha-ANP (alpha-hANP) were measured in untreated adult patients with idiopathic nephrotic syndrome (NS) and compared with those of normal volunteers (NL). The plasma concentration of immunoreactive ANP (ir-ANP) in NS (112 +/- 9.8 pg/ml, n = 9, mean +/- SE) was not significantly different from that in NL (98 +/- 8.0 pg/ml, n = 13). However, a significant positive correlation was observed between the plasma ir-ANP level and blood volume in NS (r = 0.714, p less than 0.05). In an infusion study with synthetic alpha-hANP (25 to 100 ng/kg/min), the urine flow rate increased from 0.67 +/- 0.08 to 7.11 +/- 1.08 ml/min in NL (n = 5, p less than 0.01) and from 0.64 +/- 0.16 to 2.88 +/- 0.70 ml/min in NS (n = 9, p less than 0.05) and the urinary sodium excretion increased from 115 +/- 16 to 466 +/- 62 microEq/min in NL (p less than 0.01) and from 51 +/- 8 to 207 +/- 58 microEq/min in NS (p less than 0.01). The absolute and percent changes in urine flow rate and the absolute change in sodium excretion were lower in NS (p less than 0.05) than in NL. The percent change in sodium excretion in NS did not differ from that in NL. In 2 patients with high plasma ir-ANP concentrations, however, infusion of ANP induced poor sodium excretion (59 and 95 microEq/min at 100 ng/kg/min ANP infusion, respectively). Hemodynamic and renal parameters such as blood pressure, pulse rate and creatinine clearance were similarly affected in both NL and NS. We also found that the urinary excretion of protein was significantly increased in NS (p less than 0.05) during infusion of alpha-hANP. Our data suggest that the plasma level of ir-ANP is regulated by blood volume status, and that the renal responsiveness to ANP, at least in part, contributes to water and sodium retention in NS.