Search

Administration of diuretics during acute renal failure in animals has been demonstrated to be of value with mannitol and/or loop-blocking diuretics, furosemide or ethacrynic acid. There is evidence that if these drugs are given very early in the controlled experimental environment that there will be some beneficial effect in maintaining renal function. However, in man the temporal relationship between the acute onset and the successful response to the administration of the drugs is, at best, coincidental and the use of diuretics in acute renal failure may not produce the same results as seen in the laboratory. One of the best guides to the underlying disease when there is acute decompensation in renal function is the utility of the renal failure index which utilizes urine and plasma sodium and urine and plasma creatinine ratios. Large doses of loop-blocking diuretics can be of benefit in patients with mild to moderate chronic renal insufficiency and fluid retention and/or hypertension. When renal insufficiency is severe in the pre-dialysis setting, furosemide, bumetanide or muzolimine may be of some benefit; however, as renal failure worsens the response of the kidney is sluggish and it is wise to begin to dialyze when glomerular filtration deteriorates below 5 ml per minute.

Evidence has been presented in the past that muzolimine might act at a localization differently to sulfamoyl-type diuretics and/or with a different or additional mechanism. This is further supported by the fact that at the maximum of the dose-response curves for muzolimine and furosemide in rats, a combination of maximal oral doses still results in significantly higher sodium excretion. To further substantiate that this aspect of muzolimine is of relevance, e. g. for the therapy of acute renal failure, muzolimine treatment by food or implanted osmotic minipumps was employed in an obstructive model of severe renal ischemia in rats. Acute renal ischemia was induced in Wistar rats by clamping the left renal pedicle for 60 minutes with a microsurgery clamp. The right kidney had been removed four days before ischemia. Clearance data were obtained on the first, third and on the ninth to fourteenth days after ischemia in the surviving animals. Renal ischemia resulted in anuria, increased mortality and impaired renal function with histopathologically apparent tubular obstruction in the untreated controls. Treatment with muzolimine by food (in a concentration of 800 ppm for four days) and additional oral gavage one hour prior to ischemia prevented the sequelae of ischemia to a great extent. Similar beneficial effects could be obtained by therapeutic implantation of osmotic minipumps ensuring administration of 0.44 micrograms muzolimine/h per animal. These results in rats further support the suggestion that muzolimine might act differently to sulfamoyl-diuretics. Furthermore, they strongly implicate muzolimine as the diuretic of choice in acute renal failure.

Unlabelled: The aim of this study was to test the efficiency of muzolimine in patients with acute renal failure (ARF)., Methods: 6 patients, all males, 46 to 78 years old (mean 67.3 +/- 12.5) suffering from acute renal failure as a complication of a surgical procedure (4 cases) or a medical disease (2 cases) were selected. Creatinine clearance rates were below 20 ml/min for all subjects except one (mean: 14.4 ml/min range 4-34), blood urea levels from 21 to 65 mmol/l (mean = 36.4); mean urinary output, during the 24 hours preceding the study (D-1) was 100.4 +/- 57 ml/h (range 36-208) without any diuretic treatment. No patient was on dialysis. On the treatment day a single oral dose of muzolimine (240 mg) was administered in the morning. During the treatment day (D0) and the post treatment day (D + 1), pharmacodynamics and pharmacokinetics were evaluated. Mean urinary output increased from 1.67 +/- 0.95 ml/min, at D-1 to 3.24 +/- 2 ml/min at D0 (NS), with great differences between patients. The main effect was noted between 0 and 6 hours after the ingestion of muzolimine. The mean electrolyte output increased from D0 to D1 for Na+ (0.1 mmol/min +/- 0.08----0.25 +/- 0.1-NS), K+ (0.05 mmol/min +/- 0.02----0.08 +/- 0.07-NS), Cl- (0.07 +/- 0.07 mmol/min----0.30 +/- 0.12 p less than 0.05) and Ca++ (1.89 +/- 1.89 meq/24 h----4.1 +/- 2 NS), with large individual variations. Mean urea output increased slightly in only 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)