Variability of Atrial Natriuretic Peptide Plasma Levels in Ascitic Cirrhotics: Pathophysiological and Clinical Implications

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Abstract
Ascitic cirrhotic patients are a heterogenous population with respect to factors that may affect plasma human atrial natriuretic peptide levels (such as degree of plasma volume and plasma levels of angiotensin II, vasopressin and norepinephrine). Thus the proven variability of plasma human atrial natriuretic peptide values in ascitic cirrhotic patients may be due also to the selection of patients, not only to the study conditions. The response to standardized stepped–care medical treatment of ascites makes it possible to characterize ascitic cirrhotic patients with different patterns of renal sodium excretion, intrarenal sodium handling, plasma renin activity, plasma aldosterone and thus, probably, effective circulating volume. Consequently, we evaluated human atrial natriuretic peptide plasma levels in controls (n = 23), in ascitic cirrhotic patients who underwent spontaneous diuresis (group A, n = 7) and in cirrhotic patients who required diuretic treatment (group B, n = 44). The last group was then divided into two subgroups. Subgroup B–R (n = 25) included patients who responded to spironolactone alone, whereas subgroup B–NR (n = 19) included patients who did not respond to 500 mg/day spironolactone. All patients were maintained on identical normocaloric restricted sodium intake (80 mEq/day) throughout the study. Ascitic cirrhotic patients, as a whole, had higher values of human atrial natriuretic peptide than did controls (70.8 ± 46.6 pg/ml vs. 41.7 ± 16.3 pg/ml, p < 0.025). No difference was found in human atrial natriuretic peptide/plasma renin activity between the two groups (87 ± 160 pg/ng/hr vs. 44 ± 73 pg/ng/hr, p = NS). Human atrial natriuretic peptide values in group A (n = 7) and those in group B (n = 44) were greater than those in controls (113.3 ± 63.3 pg/ml, p < 0.001, and 64.9 ± 41.4 pg/ml, p < 0.025), but they were quite different between themselves (p < 0.05). Human atrial natriuretic peptide/plasma renin activity values in group A were significantly higher than those of controls (213 ± 194 pg/ng/hr, p < 0.01) but not significantly higher than those of group B (72 ± 41 pg/ng/hr, p = NS). A significant difference was found between human atrial natriuretic peptide and human atrial natriuretic peptide/plasma renin activity values in subgroups B–R and B–NR (76.1 ± 49.4 pg/ml vs. 50.8 ± 19.4 pg/ml, p < 0.05, and 113 ± 189 pg/ng/hr vs. 20 ± 49 pg/ng/hr, p < 0.05, respectively). We concluded that plasma human atrial natriuretic peptide values may reflect different pathophysiological features in ascitic cirrhotic patients. In particular, as patients require more diuretic drugs human atrial natriuretic peptide and human atrial natriuretic peptide/plasma renin activity levels progressively fall, suggesting that patients become progressively “underfilled” and that the antinatriuretic factors predominate.