Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content

In order to clarify debated issues of the medical treatment of ascites in cirrhosis – the usefulness of a low sodium diet and washout period preceding diuretic administration, maximal dosage of antimineralocorticoid to be reached before the addition of a loop diuretic, identifications of factors influencing treatment efficacy – 115 hospitalized patients with non‐azotemic cirrhosis and ascites were recruited and randomized to receive a diet providing either 40 or 120 mmol of sodium daily. After a washout period from the outpatient diuretic regimen for 7 days (Step 1), increasing dosages of K‐canrenoate (200 mg/day every 4th day up to 600 mg) were administered to patients not undergoing spontaneous diuresis (Step 2). Upon the failure of Step 2, K‐canrenoate (400 mg/day) and furosemide at increasing dosage (25–50–100 mg every other day) were given (Step 3). Nine percent of patients underwent spontaneous diuresis, and 77% developed a negative sodium balance by the end of Step 2 (69% with a dosage of K‐canrenoate ≤400 mg/day) and 93% by the end of Step 3. Two patients were withdrawn from the protocol due to diuretic side‐effects. Univariate analysis showed that the type of diet did not influence the response to treatment. The washout period led to a significant increase in endogenous creatinine clearance; natremia significantly rose in hyponatremic patients. Multivariate analysis showed that creatinine clearance and plasma aldosterone were independent predictive factors of the response to treatment. The use of low‐sodium diet did not enhance the efficacy of the medical treatment of non‐azotemic cirrhotic ascites and a washout period from diuretics improved renal function and natremia. Antimineralocorticoids up to 400 mg/day were successful in over 2/3 of cases and the improvement in efficacy obtained by a further increase in dose was small. Endogenous creatinine clearance and plasma aldosterone significantly influenced treatment efficacy. The therapeutic regimen employed in this study was highly effective and had a very low incidence of side effects.