BACKGROUND. Injections of radiocontrast agents are a frequent cause of acute decreases in renal function, occurring most often in patients with chronic renal insufficiency and diabetes mellitus. METHODS. We prospectively studied 78 patients with chronic renal insufficiency (mean [+/- SD] serum creatinine concentration, 2.1 +/- 0.6 mg per deciliter [186 +/- 53 mumol per liter]) who underwent cardiac angiography. The patients were randomly assigned to receive 0.45 percent saline alone for 12 hours before and 12 hours after angiography, saline plus mannitol, or saline plus furosemide. The mannitol and furosemide were given just before angiography. Serum creatinine was measured before and for 48 hours after angiography, and urine was collected for 24 hours after angiography. An acute radiocontrast-induced decrease in renal function was defined as an increase in the base-line serum creatinine concentration of at least 0.5 mg per deciliter (44 mumol per liter) within 48 hours after the injection of radiocontrast agents. RESULTS: Twenty of the 78 patients (26 percent) had an increase in the serum creatinine concentration of at least 0.5 mg per deciliter after angiography. Among the 28 patients in the saline group, 3 (11 percent) had such an increase in serum creatinine, as compared with 7 of 25 in the mannitol group (28 percent) and 10 of 25 in the furosemide group (40 percent)(P = 0.05). The mean increase in serum creatinine 48 hours after angiography was significantly greater in the furosemide group (P = 0.01) than in the saline group. CONCLUSIONS. In patients with chronic renal insufficiency who are undergoing cardiac angiography, hydration with 0.45 percent saline provides better protection against acute decreases in renal function induced by radiocontrast agents than does hydration with 0.45 percent saline plus mannitol or furosemide.

OBJECTIVES: This study was done to test the hypothesis that a forced diuresis with maintenance of intravascular volume after contrast exposure would reduce the rate of contrast-induced renal injury. BACKGROUND: We have previously shown a graded relationship with the degree of postprocedure renal failure and the probability of in-hospital death in patients undergoing percutaneous coronary intervention. Earlier studies of singular prevention strategies (atrial natriuretic factor, loop diuretics, dopamine, mannitol) have shown no clear benefit across a spectrum of patients at risk. METHODS: A prospective, randomized, controlled, single-blind trial was conducted where 98 participants were randomized to forced diuresis with intravenous crystalloid, furosemide, mannitol (if pulmonary capillary wedge pressure <20 mm Hg), and low-dose dopamine (n = 43) versus intravenous crystalloid and matching placebos (n = 55). RESULTS: The groups were similar with respect to baseline serum creatinine (2.44+/-0.80 and 2.55+/-0.91 mg/dl), age, weight, diabetic status, left ventricular function, degree of prehydration, contrast volume and ionicity, and extent of peripheral vascular disease. The forced diuresis resulted in higher urine flow rate (163.26+/-54.47 vs. 122.57+/-54.27 ml/h) over the 24 h after contrast exposure (p = 0.001). Two participants in the experimental arm versus five in the control arm required dialysis, with all seven cases having measured flow rates <145 ml/h in the 24 h after the procedure. The mean individual change in serum creatinine at 48 h, the primary end point, was 0.48+/-0.86 versus 0.51+/-0.87, in the experimental and control arms, respectively, p = 0.87. There were no differences in the rates of renal failure across six definitions of renal failure by intent-to-treat analysis. However, in all participants combined, the rise in serum creatinine was related to the degree of induced diuresis after controlling for baseline renal function, r =-0.36, p = 0.005. The rates of renal failure in those with urine flow rates greater than 150 ml/h in the postprocedure period were significantly lower, 8/37 (21.6%) versus 28/61 (45.9%), p = 0.03. CONCLUSIONS: Forced diuresis with intravenous crystalloid, furosemide, and mannitol if hemodynamics permit, beginning at the start of angiography provides a modest benefit against contrast-induced nephropathy provided a high urine flow rate can be achieved.

To determine whether inhaled frusemide, a diuretic able to interfere with ion and water movement across airway epithelium, can modify exercise-induced bronchoconstriction, a three-part randomised, double-blind, placebo-controlled study was done in asthmatic patients who had a fall in FEV1 of at least 20% after running up and down a corridor. In the first part the effect of approximately 28 mg frusemide given as an aerosol was compared with that of a placebo. In the second part two doses of inhaled frusemide (approximately 14 mg and 28 mg) were examined. In the third part the effect of 20 mg oral frusemide was tested. Inhaled frusemide had a good and dose-related protective effect, whereas oral frusemide was ineffective. The mean (95% CI) maximum percentage falls in the FEV1 were: 11.5 (14.3-8.7) with frusemide and 33.8 (39.1-28.5) with placebo in the first part of the study; 13.6 (21.6-6.0) with 28 mg frusemide, 19.7 (28.2-11.3) with 14 mg frusemide, and 34.6 (39.4-30.0) with placebo in the second part of the study; and 15.2 (19.9-10.5) with inhaled frusemide, 38.2 (47.1-29.3) with oral frusemide, and 35.3 (45.9-24.7) with placebo in the last part of the study. The findings lend support to the hyperosmolarity hypothesis of exercise-induced asthma and may have therapeutic implications.

Because development of acute renal failure is one of the most potent predictors of outcome in cardiac surgery patients, the prevention of renal dysfunction is of utmost importance in perioperative care. In a double-blind randomized controlled trial, the effectiveness of dopamine or furosemide in prevention of renal impairment after cardiac surgery was evaluated. A total of 126 patients with preoperatively normal renal function undergoing elective cardiac surgery received a continuous infusion of either "renal-dose" dopamine (2 microg/kg per min)(group D), furosemide (0.5 microg/kg per min)(group F), or isotonic sodium chloride as placebo (group P), starting at the beginning of surgery and continuing for 48 h or until discharge from the intensive care unit, whichever came first. Renal function parameters and the maximal increase of serum creatinine above baseline value within 48 h (deltaCrea(max)) were determined. The increase in plasma creatinine was twice as high in group F as in groups D and P (P < 0.01). Acute renal injury (defined as deltaCreamax)>0.5 mg/dl) occurred more frequently in group F (six of 41 patients) than in group D (one of 42) and group P (zero of 40)(P < 0.01).(The difference between group D and group P was not significant.) Creatinine clearance was lower in group F (P < 0.05). Two patients in group F required renal replacement therapy. The mean volume of infused fluids, blood urea nitrogen, serum sodium, serum potassium, and osmolar- and free-water clearance was similar in all groups. It was shown that continuous infusion of dopamine for renal protection was ineffective and was not superior to placebo in preventing postoperative dysfunction after cardiac surgery. In contrast, continuous infusion of furosemide was associated with the highest rate of renal impairment. Thus, renaldose dopamine is ineffective and furosemide is even detrimental in the protection of renal dysfunction after cardiac surgery.

Loop and distal diuretics are the basic drugs for the treatment of ascites. Although pharmacologic studies indicate that the natriuretic potency of loop diuretics is much greater than that of distal diuretics, there are no studies comparing the efficacy of these drugs in cirrhosis. Forty nonazotemic cirrhotic patients with ascites and avid sodium retention were randomly allocated into two groups. Group 1 contained 21 patients treated with furosemide; group 2 contained 19 patients treated with spironolactone. The initial doses were 80 and 150 mg/day, respectively. These doses were increased to 160 and 300 mg/day, respectively, if there was no response. Cases not responding to furosemide and spironolactone were later treated with spironolactone and furosemide, respectively. In group 1, 11 of the 21 patients responded to furosemide, while in group 2, 18 of the 19 patients responded to spironolactone (p less than 0.01). Of the 10 patients in group 1 not responding to furosemide, 9 responded later to spironolactone. The diuretic response to furosemide and spironolactone was related to the activity of the renin-aldosterone system. Patients with higher renin and aldosterone did not respond to furosemide and required 300 mg/day of spironolactone to achieve a diuretic response. These results indicate that (a) at the dosages used in the study, spironolactone is more effective than furosemide in nonazotemic cirrhosis with ascites, and (b) the activity of the renin-aldosterone system influences the diuretic response to furosemide and spironolactone in these patients.

PURPOSE: To evaluate the clinical utility and morphologic accuracy of gadolinium-enhanced excretory magnetic resonance (MR) urography after low-dose diuretic injection and to correlate the results with those of conventional urography. MATERIALS AND METHODS: In 71 patients with urologic symptoms, excretory MR urography was performed after intravenous injection of 5-10 mg furosemide and, 30-60 seconds later, 0.1 mmol of gadopentetate dimeglumine per kilogram of body weight. The MR urograms were interpreted by three radiologists, who were blinded to the clinical outcome, and subsequently compared with conventional urograms. RESULTS: Injection of furosemide before contrast material led to rapid, uniform gadolinium distribution inside a sufficiently distended collecting system such that there was no excessive concentration of gadolinium in the urine. In patients with normal or moderately reduced excretory function, this effect allowed complete visualization of the urinary tract within 5-20 minutes of contrast material injection while minimizing gadolinium-related endoluminal T2* effects. The clinical course helped verify almost all MR urographic results. The MR urographic technique was significantly superior to conventional urography in the assessment of the ureters and bladder (P <.0001). Delineation of small caliceal abnormalities is still problematic. The best depiction of the pelvicaliceal system was obtained with fat-suppressed MR imaging, although it was still slightly inferior to conventional urography (P <.05). CONCLUSION: Gadolinium-enhanced excretory MR urography performed after low-dose diuretic injection is a promising and accurate alternative to conventional excretory urography for imaging the morphology of the urinary tract.

To identify patients with low-renin hypertension, we measured plasma renin activity after the administration of 40 mg of furosemide intravenously and 30 minutes of upright posture in 127 normotensive subjects and 363 patients with essential hypertension. Plasma renin activity 30 minutes after intravenous furosemide was found to be closely correlated to the level found after either 2 or 4 h of standing or 3 days of a low-salt diet plus 2 h of upright posture. Renin responsiveness was significantly lower in hypertensive patients, blacks, and women, compared with normotensive subjects, whites, and men respectively. The level of plasma renin activity in most normal white subjects was greater than 1.0 ng/ml - h and in most normal blacks was greater than 0.5 ng/ml - h. It was below those levels in 23% of white hypertensive and 25.2% of black hypertensive patients respectively. The mean level of plasma renin activity fell with increasing age of hypertensive patients. This procedure is recommended as a safe, easy, and reliable test for assessing renin responsiveness and identifying the low-renin state.

OBJECTIVES: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF). BACKGROUND: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial. METHODS: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration. RESULTS: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration. CONCLUSIONS: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.

After an oral or intravenous dose of furosemide, there is considerable interindividual variability in the amount of unchanged drug delivered into the urine. On average, approximately half as much reaches the intraluminal site of action with an oral compared to an intravenous dose. However, the natriuretic response to the same dose administered by either route is virtually the same. Similarly, after pretreatment with probenecid, the same total amount of furosemide in urine causes a greater overall response. It has been presumed that this paradox is accounted for by differences in rate of delivery of furosemide to the active site such that after an oral dose, or after pretreatment with probenecid, amounts of drug are for longer periods of time at the "steep" portion of the dose-response curve. Our analysis shows this not to be the case. For furosemide, the "slope factor" of the dose-response curve is such that the amount of diuretic delivered into the urine which is maximally efficient (21.5 micrograms/min) is considerably less than the amount causing half-maximal response (69.8 micrograms/min). Oral administration or pretreatment with probenecid maintains drug close to this maximally efficient amount more persistently than does intravenous administration. By so doing, total response to an oral dose approaches that of intravenous dosing despite delivering half the amount of drug to the active site, and after probenecid an intravenous dose causes a greater response than intravenous dosing alone despite delivering the same amount of drug to the active site. These data emphasize the importance of the time course of delivery of drug to the active site as an independent determinant of overall response.

Minoxidil in combination with propranolol and diuretics controlled the blood-pressure in a group of hypertensive patients who were resistant to treatment with large doses of standard drugs. The main problem was fluid retention but subjective side-effects were fewer than in a comparable group on other drugs.