Atrial natriuretic peptide, sodium retention, and proteinuria in nephrotic syndrome

Oedema formation in the nephrotic syndrome is primarily due to tubular sodium retention. The pathogenetic role of alpha atrial natriuretic peptide (ANP), a hormonal promoter of natriuresis is unknown.

In 31 patients (aged 35+/-11 years) with nephrotic syndrome and histopathological evidence of primary glomerulonephritis, we investigated plasma ANP concentration and its influence on renal haemodynamics, natriuresis, and proteinuria (total protein, albumin, IgG excretion). Patients with a compensated treated form of nephrotic syndrome due to primary glomerulonephritis were included in the study. Serum creatinine levels were <=1.4 mg/dl. Diuretic medication was discontinued at least 24 h before the investigation was started. Patients were randomly assigned to ANP infusion (0.005 microg/kg*min; group II, n=15) or received placebo (group III, n=16). Ten healthy subjects (group I) served as normal controls.

In normal subjects (group I), ANP caused an increase in natriuresis from 14.5+/-4.2 mmol/h to 26.4+/-11.1 mmol/h (P<0.01). In patients with nephrotic syndrome (group II), baseline sodium excretion of 10.5+/-6.0 mmol/h was increased to 19.6+/-14.8 mmol/h with ANP infusion (P<0.01). No changes were seen in the placebo group III. The absolute increase in ANP induced natriuresis was not significantly different between group I and II. However, plasma ANP levels were significantly higher in patients with nephrotic syndrome (166+/-87 pg/ml vs. 74+/-21 pg/ml, P<0.05) and also reached higher levels after ANP infusion (P<0.01). Therefore, natriuresis was significantly reduced when circulating ANP levels were taken into account (P<0.05). ANP administration resulted in an increase of total protein excretion in patients with the nephrotic syndrome (group II, from 219+/-277 mg/h to 264+/-268 mg/h). Albumin elimination rose from 128+/-151 mg/h to 167+/-170 mg/h (P<0.05) and IgG excretion from 4.91+/-6.67 mg/h to 9.27+/-10.78 mg/h (P<0.05). Healthy subjects also showed a small but significant increase in albuminuria (48+/-38%, P<0.05). Low-dose ANP infusion did not, however, induce any significant alteration in GFR, ERPF and blood pressure.

ANP plasma concentrations in the steady state are elevated in patients with the nephrotic syndrome. The natriuretic effect of ANP is reduced when referring to circulating ANP plasma levels. Elevated ANP levels enhance urinary protein excretion in the nephrotic syndrome. This is not due to modulation of GFR or FF, but is most probably attributable to increased glomerular permeability.