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PubMed1994

Renal excretion of endothelin in children is influenced by age and diuresis.

Endothelin is a peptide with vasoactive and diuretic potential. Its release has been demonstrated from endothelial and renal epithelial cells. Urinary excretion of endothelin, as shown by others, is thought to reflect intrarenal production. We measured endothelin by RIA in a population of healthy children from Germany and Hungary (group 1), neonates (group 3) and children before and during forced diuresis (groups 2a and 2b). Group 1 consisted of 24 children living in Germany and 13 children resident in Hungary. The age range in this group was 2.9-17 years. Daily excretion correlated significantly with age (r = 0.48, p < 0.001), but endothelin excretion corrected for body surface area remained constant with regard to the age group studied. This indicates that body or kidney size may influence endothelin excretion, respectively. There was no difference in endothelin excretion between the two countries. In premature infants and neonates (group 3), daily excretion of endothelin was highest in infants with very low gestational ages and decreased in full-term neonates to values not significantly different to the group of older children. The high values in premature infants may have been influenced by mechanical ventilation of physical stress, which cannot be differentiated in this study, however. In contrast to reported results in adults, renal excretion of endothelin was correlated positively to urine flow in all groups. Furthermore, the influence of forced diuresis was evaluated in 10 children with oncological disease before (group 2a) and during (group 2b) forced diuresis with fluid load (3 l/m2; n = 4) and fluid load with furosemide injection (0.3-1.0 mg/kg body weight; n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1978

The value of provocative and acute urography in patients with intermittent loin pain.

Twenty-two patients with intermittent loin pain thought to be typical of primary pelvic hydronephrosis but with normal appearances at standard excretion urography were subjected to diuretic urography using Frusemide-induced diuresis. If this was normal, acute urography was performed when the patient had pain. Abnormal appearances were shown in only 15 patients. In 4, only the erect films revealed the hydronephrosis. Dilatation occurred in response to a diuretic load in 9 and the abnormality was shown at the time of an attack of pain in 4. The hydronephrosis was shown only during the attack of pain in 2, a diuretic urogram having been normal. In 2 patients the nephrographic signs of acute obstruction were shown to be due to occlusion of the pelvi-ureteric junction at the time of an attack of pain. The importance of sequential examination, the value of erect films and acute urography are stressed.

Diuresis↗
PubMed1977

Study of the sites and mechanisms of action of bumetanide in man.

Acute clearance studies were performed in normal subjects to establish the site(s) and mechanism of action of the new diuretic agent, bumetanide (3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid), in the human kidney. When the drug was administered during water diuresis, solute-free water formation was unchanged associated with a peak increment in fractional sodium excretion of approximately 15% of filtered load. However, studies performed in hydropenic subjects demonstrated a virtual abolition of free water reabsorption. The diuretic caused a mild phosphaturia which did not appear to be related to alterations in parathyroid hormone. Furthermore, whereas net hydrogen ion excretion and urinary pH were unchanged, the excretion of ammonium ion, titratable acidity and bicarbonate all increased mildly. Taken together, the data suggest that the primary site of action of bumetanide is the medullary portion of the ascending limb of the loop of Henle, but that in addition, bumetanide inhibits the transport of sodium in the proximal nephron. Despite the fact that the drug is a sulfonamide derivative, its proximal activity seems unrelated to a carbonic anhydrase inhibitory effect. More likely the agent interferes with proximal reabsorption by impairing sodium-phosphate linked transport.

Administration, Oral↗
PubMed1975

[Use of aldactone-saltucine in patients with heart failure].

Aldactone-saltucine was used in 52 patients with Stage IIB-III cardiac failure. The efficiency of the drug was evaluated by the dynamics of the clinical course, diuresis, body weight, blood and urine levels of electrolytes, and in some patients by the urine excretion of aldosterone. Aldactone-saltucine is a sufficiently effective diuretic agent that, without producing excessively fast diuresis, exerts after a course of therapy a beneficial effect, increasing mainly natriuresis, without concomitant hypokalemia. The diuretic effect of the drug ensued irrespectful of the initial level of urine aldosterone excretion. After a course of treatment urine aldosterone excretion tended to increase. Hyperaldosteronuria was noted in only 1/3 of the patients.

Adult↗
PubMed1980

Blunting of furosemide diuresis by aspirin in man.

Experiments were performed on humans to study the blunting on the diuretic action of furosemide by prostaglandin synthetase inhibitors. Maximal water diuresis was instituted. At the peak of urine flow, clearance periods were performed during baseline conditions and repeated after the injection of aspirin and, subsequently, of furosemide. Control subjects did not receive aspirin. Urine flow rate (V), Cosm, and Na excretion (UNa) . V were significantly lower when the administration of the diuretic had been preceded by that of aspirin. In the absence of furosemide, however, aspirin did not influence renal hemodynamics nor Na and water reabsorption. Therefore, the same experimental protocol was repeated in paired experiments where each normal subject served as his own control, being studied twice, in the presence and absence of aspirin, respectively. The average changes in water and Na excretion induced by furosemide were not different when the patients were pretreated with aspirin as compared with those measured in the absence of prostaglandin inhibition. Changes occurring in individual experiments were significantly correlated (r = 0.95, P less than 0.01) with those in calculated furosemide clearance. Since aspirin, indomethacin, and meclophenamate are secreted by the organic acid transport system of the proximal tubule, competition for a common secretory mechanism, rather than prostaglandin inhibition, could mediate the blunting of furosemide diuresis.

Aspirin↗
PubMed1998

Low-dose theophylline increases urine output in diuretic-dependent critically ill children.

OBJECTIVE: Determine the effect of low-dose theophylline on urine output and the urinary adenosine: cAMP (cyclic adenosine monophosphate) excretion ratio (a measure of phosphodiesterase inhibition) in diuretic-dependent critically ill children. DESIGN: Observational clinical case series and animal laboratory experiment. SETTING: A university pediatric intensive care unit and a pharmacology research laboratory. PATIENTS: 10 consecutive oliguric patients treated with theophylline for diuresis. INTERVENTIONS: Urine output, fluid intake, diuretic dosages, and number of pressors (including dopamine) were monitored over the 24-h period prior to and the 24-h period immediately after theophylline was started. Hourly collections of urine were obtained at baseline and 1 and 3 h after theophylline was started and urinary excretion rates of adenosine and cAMP were measured and calculated. MEASUREMENTS AND RESULTS: Mean theophylline level in the children was 5.0 microg/ml. Urine output increased from 1.58 +/- 0.46 to 3.75 +/- 0.77 ml/kg per h (p = 0.008, paired t-test) after theophylline administration. There was no significant change in fluid intake, vasoactive agents, or dosages of other diuretics during the study periods. Intrarenal infusion of the IC50 concentration of isobutylmethylxanthine for phosphodiesterase activity resulted in a reduction of the adenosine: cAMP urinary excretion ratio in rats (p < 0.05). Low-dose theophylline had no effect on the adenosine: cAMP urinary excretion ratio in children. Concurrent therapy with dopamine was associated with an enhanced diuretic effect of theophylline (with dopamine, 1.30 +/- 0.30 to 5.07 +/- 0.77 ml/kg per h vs without dopamine, 1.77 +/- 0.76 to 2.86 +/- 1.08 ml/kg per h; p = 0.03, two-way ANOVA). There was no interaction between dopamine and low-dose theophylline on the urinary adenosine: cAMP excretion ratio (p = 0.56, two-way ANOVA). CONCLUSIONS: Theophylline increased urine output in diuretic-dependent critically ill children and the diuretic effect may have been potentiated by concurrent use of dopamine. Adenosine receptor antagonism may be a more likely mechanism for the diuretic effect of theophylline than phosphodiesterase inhibition.

Adenosine↗
PubMed1980

Role of angiotensin II and bradykinin in the diuresis caused by stimulation of atrial receptors.

The diuretic response to stimulation of left atrial receptors, by distending balloons located either at the pulmonary vein-left atrial junctions or in the body of the left atrium, was studied during blockade of the generation of angiotensin II using a continuous infusion of angiotensin converting enzyme inhibitor, SQ 14,225, in anaesthetized dogs. Despite blockade of angiotensin conversion, known also to potentiate the activity of bradykinin, a diuretic response was obtained in each dog; the response was similar to that observed in dogs without blockade of angiotensin conversion. Angiotensin II and bradykinin did not significantly influence the rate of secretion of Malpighian tubules of Rhodnius prolixus, which have been shown capable of detecting the blood-borne agent known to mediate the diuretic response. It is concluded that neither angiotensin II nor bradykinin is likely to be the blood-borne agent released by stimulation of atrial receptors.

Angiotensin II↗
PubMed1989

Studies on the adrenomedullary dependence of kappa-opioid agonist-induced diuresis in conscious rats.

1. The dependence of kappa-opioid agonist-induced diuresis, upon an intact and functional adrenal medulla in conscious rats, was investigated in order to test the hypothesis that the diuresis is mediated by a blood-borne 'diuretic factor', of adrenomedullary origin, released by kappa-opioid receptor stimulation. 2. Confirming previous observations, adrenal demedullation significantly attenuated diuretic responses to the kappa-opioid agonists U50488H, ethylketocyclazocine (EKC) and tifluadom, but did not affect basal urine output, furosemide-induced diuresis or the antidiuretic response to the mu-opioid agonist, buprenorphine. Naloxone abolished U50488H-induced diuresis, confirming an involvement of opioid receptors. 3. Transfusion studies established that blood, from intact rats treated with U50488H, induced diuresis in intact and demedullated recipient rats, whether or not the recipients had been pretreated with naloxone. However, blood from demedullated rats treated with U50448H was unable to induce diuresis when administered to intact or demedullated recipients. 4. It is concluded that kappa-opioid agonist-induced diuresis is dependent upon an intact and functional adrenal medulla and appears to be mediated by a blood-borne 'diuretic factor' of adrenomedullary origin.

Adrenal Medulla↗
PubMed1970

Spironolactone diuresis in patients with cirrhosis and ascites.

Increased aldosterone levels with consequent or diuretic-potentiated electrolyte abnormalities are an important consideration when patients with cirrhosis and ascites undergo diuresis. A simple clinical method using the urinary Na/K ratio as a guide to spironolactone dosage is outlined. Patients with a ratio greater than 1 responded well to 100 mg. of spironolactone a day; those when it was one or less responded well to 200 to 1,000 mg. a day.Administration of spironolactone alone (11 patients) or as the main diuretic (three patients) was a safe and effective means of inducing sustained uncomplicated diuresis in all these patients.

Alcoholism↗
PubMed1998

Coadministration of theophylline enhances diuretic response to furosemide in infants during extracorporeal membrane oxygenation: a randomized controlled pilot study.

OBJECTIVE: This pilot study evaluates the efficacy of low-dose theophylline administered before furosemide to enhance diuresis in neonates recovering from fluid retention during extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Infants receiving ECMO (n = 24) were randomized (double blind, placebo-controlled) to receive either regimen A (placebo/furosemide day 1, theophylline/furosemide day 2, placebo/furosemide day 3) or regimen B (theophylline/furosemide day 1, placebo/furosemide day 2, theophylline/furosemide day 3). Urine flows and renal functions were compared. RESULTS: Urine flow rate before initiation of diuretic therapy was not significantly different between groups A and B (2.6 +/- 1.4 vs 3.5 +/- 1.3 ml/kg/hr, respectively, p = 0.12). Infants who received theophylline/furosemide had significantly higher urine flow rates than those who received placebo/furosemide on day 1 (11.8 +/- 4.6 vs 7.2 +/- 2.4 ml/kg/hr, p < 0.01). The 24-hour fluid volumes and balances became significantly more negative with theophylline enhancement of furosemide's effect. There were no significant differences in renal function between the two groups. CONCLUSION: Low doses of theophylline given before furosemide administration significantly enhance diuretic response in infants with fluid retention during ECMO.

Diuresis↗
PubMed2006

[Diuretic effect of an infusion of the herbal plant, Salvia scutellarioides, in rats].

INTRODUCTION: In the Colombian traditional medicine, an infusion made of the entire plant Salvia scutellarioides (known locally as mastranto or oreja de perro (dog's ear)) is used for its antihypertensive and diuretic effects. However, experimental studies have never been done to validate the reported effects. OBJECTIVE: In the current study, a rat model was used to determine the effect of S. scutellarioides on rat diuresis and urinary electrolytes concentration. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were distributed in four groups: Group 1--normal saline solution, Group 2--furosemide (10 mg/kg), Groups 3 and 4 with S. scutellarioides infusion, 1 g/kg and 2 g/kg respectively. All treatments were administered in a volume of 25 ml/kg of rat weight. After treatment, the rats were placed in a metabolic cage for 6 hours. During this period, urinary excretion was monitored and quantified. At the end of 6 hours, the urinary electrolyte concentrations were measured. RESULTS: The administration of S. scutellarioides at doses of 1 and 2 g/kg produced a significant increase in diuresis when compared to the control group (p < 0.01). The administration of S. scutellarioides at these doses also increased the urinary excretion of potassium and chloride. CONCLUSIONS: These results corroborate the apparent diuretic activity of S. scutellarioides described by traditional herbalists and possibly explains its reported antihypertensive effect. Further studies are required to determine the pharmacological and toxicological profile of the plant.

Animals↗
PubMed1985

Determination of renal function following urinary diversion through intestinal segments.

Serum concentrations of urea and creatinine, urinary clearances of urea and creatinine, and urine concentrating ability have been proposed as measures for determining renal function in patients with urinary diversion through intestinal segments. Intestinal segments reabsorb urinary solutes, including urea and creatinine, complicating these methods of assessing renal function. This study employs a canine model in which urinary clearances of urea, creatinine and inulin are determined through a normal renal unit and ureter and compared with the contralateral renal unit which has had its ureter replaced by a segment of ileum. Urea, creatinine and inulin are reabsorbed by the ileal segment. Reabsorption of each of these solutes is dependent on urinary flow. The clearance of these solutes through the renal unit with the interposed ileal ureter approaches that of the contralateral renal unit under maximal degrees of diuresis. Creatinine and inulin clearances obtained during diuretic states give the most accurate indication of true renal function. These solutes are reabsorbed to a lesser extent than urea. Diuresis minimizes reabsorption of all these solutes by the ileal segment. Urine concentration does not reflect distal tubule function since the ileal segment reabsorbs urinary solutes and is freely permeable to water.

Animals↗
PubMed1980

Effect of osmotic diuresis on gentamicin-induced nephrotoxicity in rats.

The effect of isosorbide diuresis on gentamicin excretion and tissue accumulation as well as gentamicin-induced histopathologic changes in renal tissue were examine in rats. Gentamicin (30, 60, 120, 160 mg/kg) was administered s.c. for 10 consecutive days with or without isosorbide pretreatment. Osmotic diuresis with isosorbide did not significantly reduce the dose-dependent extent of gentamicin accumulation in renal tissues in comparison to nondiuresed rats. Although the urinary concentration of gentamicin was reduced in the diuresed animals, total gentamicin excretion remained unaffected. In addition, diuresis altered neither the renal excretion of the proximal tubular cell marker enzyme, N-acetyl-B-glucosaminidase, nor the severity of pathologic damage as determined by light microscopic examination of renal tissues. It appears that osmotically-induced diuresis alone is insufficient to prevent or significantly reduce gentamicin nephrotoxicity in rats. This is in contrast to other forms of diuretic therapy, such as furosemide, which have been shown to effectively reduce renal accumulation and resultant renal toxicity of aminoglycoside administration.

Acetylglucosaminidase↗
PubMed1968

Effects of water diuresis and osmotic (mannitol) diuresis on urinary solute excretion by the conscious rat.

1. The time course and extent of changes in urinary flow and in the outputs of urea, Na(+), K(+), and NH(4) (+) over a period of 7(1/2) hr in conscious rats during water and osmotic (mannitol) diuresis were determined, and compared with spontaneous changes in non-diuretic animals.2. In non-diuretic rats, a morning rise and subsequent decline in urinary osmolal, sodium, potassium and ammonium outputs occurred, possibly attributable to circadian rhythms.3. Water diuresis was accompanied by (i) a rapid increase in urea excretion during the phase of increasing urine flow, followed by a fall in later periods to values similar to those in non-diuresis, (ii) a slower increase in sodium output, continuing after the establishment of the constant water load, (iii) unchanged potassium excretion, but slightly increased ammonium outputs.4. Mannitol diuresis was accompanied by (i) a rapid increase in urea outputs which subsequently fell but remained significantly higher, (ii) a steep rise in sodium and potassium outputs to values which remained far higher than those in non-diuretic and water diuretic animals.5. The changes in mannitol diuresis are considered to result mainly from decreased tubular reabsorption, due to the lowered intraluminal sodium, potassium and urea concentrations and increased intratubular fluid flow. Some of the acute increase in urea excretion may be due to washout of medullary urea into the tubular fluid.6. In water diuresis, some of the changes in solute excretion may similarly result from altered tubular reabsorption, perhaps influenced by suppression of anti-diuretic hormone (A.D.H.). In addition, the slower changes in sodium output may be related to several consequences of change in body fluid volume.

Ammonia↗
PubMed1982

Piretanide (HOE 118) in dogs.

Piretanide, a "loop" diuretic, was administered orally and IV at 3 dose levels to healthy Beagles. The effects were measured over an 8-hour period. A marked diuresis occurred with both methods of administration at all dose levels. It was characterized by increased excretion of Na+, Cl-, and, to a lesser extent, K+. Urine osmolality and specific gravity decreased significantly, while urine Na+ and K+ concentrations decreased concurrently. Changes from base lines were not detected in hematologic values, except for serum K+ which reached below base line with larger doses. Piretanide is a potent diuretic and treated patients should be monitored for hypokalemia.

Administration, Oral↗
PubMed2000

Input rate as a major determinant of furosemide pharmacodynamics: influence of fluid replacement and hypoalbuminemia.

To investigate how the response to a bolus and an infusion of furosemide is modulated by the rate of fluid replacement and by hypoalbuminemia, rabbits received 5 mg/kg of furosemide as a bolus or infused over 60 min, whereas diuresis was replaced with 13, 121, or 238 ml/h NaCl 0.9%/glucose 5% (50:50). Natriuretic and diuretic efficiencies were greater with the infusion than with the bolus of furosemide. Fluid replacement increased natriuretic and diuretic efficiency of furosemide bolus but only diuretic efficiency of furosemide infusion. Furosemide net fluid depletion reached a plateau when fluid replacement increased beyond 121 ml/h. Repeated plasmapheresis decreased plasma albumin by 30% (P <.05) and increased furosemide unbound fraction (P <.05). Compared with control rabbits, hypoalbuminemia decreased the natriuresis of the bolus (22.7 +/- 1.5-16.6 +/- 1.3 mmol, P <.05) but not that elicited by furosemide infusion (26.2 +/- 1.8 mmol). Given as a bolus, furosemide natriuretic and diuretic response as a function of its urinary rate of excretion exhibited an hyperbolic relationship, and after its infusion a clockwise hysteresis, denoting tolerance. Plasma renin activity was increased by the bolus and the infusion of furosemide, even in the presence of 121 ml/h of fluid replacement. It is concluded that: 1) the increase in natriuretic/diuretic efficiency of the bolus induced by fluid replacement is greater than when furosemide is infused, 2) furosemide net effect does not increase proportionally to fluid replacement, and 3) the infusion of furosemide prevents the hypoalbuminemia-induced decrease in response of furosemide given as a bolus.

Animals↗
PubMed1986

Rapid diuresis in patients with ascites from chronic liver disease: the importance of peripheral edema.

Serial measurements of plasma volume and ascites volume were made during treatment with large doses of oral diuretics in 14 patients with stable chronic liver disease. Eight patients had pitting edema in addition to ascites. Reproducibility of ascites and plasma volume measurements was verified in 10 control subjects not receiving diuretics. Six patients without edema undergoing rapid diuresis lost a mean of 1.2 +/- 0.2 L of ascites and an equivalent amount of weight (1.3 +/- 0.4 kg) per day. All had a rise in blood urea nitrogen or creatinine, or both, and a fall in creatinine clearance. Eight patients with edema undergoing rapid diuresis lost more weight (1.8 +/- 0.5 kg/day, p = 0.06) but less ascites (0.7 +/- 0.35 L/day, p less than 0.05) than those without edema, and none developed renal insufficiency. After edema disappeared, ascites mobilization increased (1.4 +/- 0.7 L/day) and renal dysfunction occurred. Plasma volume fell an average of 24% +/- 9% in patients without edema but did not change in patients with edema (-0.4% +/- 3%). When edema disappeared, plasma volume fell significantly (28% +/- 8%, p less than 0.001). Electrolyte changes including hyponatremia, hyperkalemia, and hypochloremia were seen only in the group without edema. Patients with ascites and no edema are able to mobilize more than 1 L/day during rapid diuresis, but at the expense of plasma volume contraction and renal insufficiency. Patients with peripheral edema appear to be protected from these effects because of the preferential mobilization of edema and may safely undergo diuresis at a rapid rate (greater than 2 kg/day) until edema disappears.

Amiloride↗
PubMed1980

Demeclocycline therapy for resistant oedema in advanced cardiac failure.

A patient with long-standing ischaemic heart disease and severe low output congestive cardiac failure received numerous diuretics, which gradually became ineffective. Resistant oedema was treated by adding demeclocycline to the current diuretic regime of frusemide and metolazone. Diuresis resulted, oedema disappeared and body weight fell. This drug combination was continued without complication for a further 6 months until his death.

Demeclocycline↗