title: Refractory ascites: modulation of atrial natriuretic factor unresponsiveness by mannitol.
abstract: We have previously shown that unresponsiveness to atrial natriuretic factor is a marker of the severity of ascites. The tubular mechanisms are unknown, but it seems that increased reabsorption of sodium proximal to the main site of action of atrial natriuretic factor (i.e., the inner medullary collecting duct) plays an important role. We attempted to decrease the proximal reabsorption of sodium with mannitol in patients unresponsive to atrial natriuretic factor. The results of mannitol in such a group of patients has previously been conflicting. We studied 10 patients with massive, resistant ascites who were off diuretics and on a 20-mmol/day sodium diet for 7 days. Atrial natriuretic factor unresponsiveness was confirmed by failure of a 2-hr atrial natriuretic factor infusion to induce a natriuresis. The next day all patients received an infusion of 40 gm of mannitol and subsequently a combined infusion of mannitol and atrial natriuretic factor. Proximal reabsorption of sodium and water were evaluated by lithium clearance, and glomerular filtration rate and renal blood flow were evaluated by inulin clearance and p-aminohippurate clearances, respectively. Six patients responded to mannitol alone with an increased diuresis (from 39 +/- 7 to 148 +/- 35 ml/hr) and natriuresis (from 0.27 +/- 0.05 mmol/hr to 1.65 +/- 0.53 mmol/hr; p less than 0.05) (responders), whereas four did not (nonresponders). The combination of atrial natriuretic factor and mannitol induced a further significant increase in sodium excretion (3.28 +/- 0.68 mmol/hr) but not in urine excretion, compared with mannitol alone.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Toronto, Canada.
authors.forename: G A
authors.initials: GA
authors.lastname: Morali
authors.forename: S W
authors.initials: SW
authors.lastname: Tobe
authors.forename: K L
authors.initials: KL
authors.lastname: Skorecki
authors.forename: L M
authors.initials: LM
authors.lastname: Blendis
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D001201:Ascites / Q000503:physiopathology; D001219:Aspartate Aminotransferases / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage; D001663:Bilirubin / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008094:Lithium / Q000493:pharmacokinetics; D008103:Liver Cirrhosis / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000503:physiopathology / Q000652:urine; D008353:Mannitol / Q000008:administration & dosage; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011517:Prothrombin Time; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine
chemical_list: D008353:Mannitol; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D008094:Lithium; D012964:Sodium; D001219:Aspartate Aminotransferases; D012083:Renin; D001663:Bilirubin; D009638:Norepinephrine