REFRACTORY ASCITES IN CIRRHOSIS - ROLES OF VOLUME EXPANSION AND PLASMA ATRIAL-NATRIURETIC-FACTOR LEVEL ELEVATION

Cirrhotic patients with ascites refractory to diuretics also have blun ted response to marked elevations of plasma atrial natriuretic factor levels alone or to moderate intravascular volume expansion by head-out water immersion. However, these patients usually undergo natriuresis after peritoneovenous shunting. To dissect the factors responsible for this response, we studied the effects on separate days of moderate in travascular volume expansion and highly elevated plasma atrial natriur etic factor levels (head-out water immersion and atrial natriuretic fa ctor infusion) or marked volume expansion and moderate plasma atrial n atriuretic factor level elevation (head-out water immersion and albumi n infusion) in 13 alcoholic cirrhotic patients with massive ascites. T hree of these patients, who responded to initial head-out water immers ion with a negative sodium balance, served as controls. Unresponsivene ss to head-out water immersion was confirmed in the remaining 10 patie nts on both days on the basis of blunted natriuretic response (urinary sodium excretion < 0.8 mmol/hr after 2 hr). In contrast, these 10 ref ractory patients were able to achieve negative sodium balance with bot h combinations. Mean urinary sodium excretion increased from a baselin e level of 0.13 +/- 0.10 mmol/hr to a peak level of 2.29 +/- 0.61 mmol /hr after head-out water immersion and atrial natriuretic factor infus ion and from 0.10 +/- 0.3 mmol/hr to 1.61 +/- 0.62 mmol/hr after head- out water immersion and albumin infusion. Both maneuvers were associat ed with suppression of plasma renin activity and serum aldosterone lev els. With head-out water immersion and atrial natriuretic factor infus ion, we noted a significant increase in 5' cyclic GMP levels, a second messenger of atrial natriuretic factor, indicating possible activatio n of atrial natriuretic factor receptors at the inner medullary collec ting ducts. In contrast, with head-out water immersion and albumin inf usion no such increase in levels occurred, indicating that the increas e in urinary sodium excretion was mainly due to increased delivery of sodium to the cortical distal nephron, as indicated by a disproportion ate increase in urinary potassium excretion. In conclusion, massive (a s opposed to moderate) volume expansion or greatly elevated levels of plasma atrial natriuretic factor associated with moderate volume expan sion can improve blunted atrial natriuretic factor responsiveness in c irrhotic patients with refractory ascites. This appears to be achieved by way of a marked increase in distal delivery of filtrate in the kid ney, with or without activation of distal atrial natriuretic factor re ceptors in the inner medullary collecting ducts.