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Comparison of diuretic effects of glycerol with furosemide after transurethral prostatectomy.

BACKGROUND: Diuretic therapy after transurethral prostatectomy (TURP) is primarily intended to induce diuresis against water intoxication and cystic clot retention. This study was undertaken to compare the diuretic effects of glycerol with furosemide after TURP. METHODS: Thirty patients (ASA I or II) undergoing TURP were studied. Spinal anesthesia was induced with bupivacaine. At the end of prostatic resection, the patients were randomly allocated into two groups. In one group (n = 15) the patients received furosemide 30 mg i.v., while in the other group (n = 15) they received glycerol 0.5 g/kg i.v. Blood samples were collected for measurements of osmolality, hematocrit, sodium and glucose concentration before anesthesia and after surgery. Urine output was also recorded after surgery in each group. RESULTS: Plasma osmolality in glycerol group was higher than furosemide group at 30 min (295.3 +/- 10.6 vs. 283.8 +/- 5.6 mOsm/kg, p < 0.01) and 1 h after operation (294.9 +/- 8.7 vs 286.3 +/- 6.7 mOsm/kg, p < 0.01). Blood glucose was higher in glycerol group than that in furosemide group at 2 h after operation (195.6 +/- 121.9 vs 152.9 +/- 70.1 mg/dl, p < 0.05). Measured urine output was significantly greater in furosemide group at 30 min after operation (904.6 +/- 491.5 vs. 248.4 +/- 143.4 ml, p < 0.05) but was greater in glycerol group at 12 h after operation. CONCLUSIONS: Since urine output is significantly less in glycerol group at 1 h after operation, glycerol is inferior to furosemide for preventing cystic clot retention after TURP. But glycerol may protect against water intoxication better for its merit of producing higher plasma osmolality.

Aged↗

Do diuretics differ in terms of clinical outcome in congestive heart failure?

Diuretics are required in the majority of patients with symptomatic congestive heart failure (CHF). The reduction of pulmonary venous congestion results in rapid improvement of dyspnoea and increased exercise tolerance. In contrast to arterial hypertension, there are only a few studies comparing diuretics with other drugs in CHF. In particular, no reliable data exist on the effect of diuretics on mortality and major cardiac events in CHF. Diuretic agents differ in their mode of action, pharmacodynamics and pharmacokinetic properties. Loop diuretics are used in acute CHF and in severe chronic CHF, while thiazides, having a longer duration of action, are suitable for long-term therapy of mild CHF in ambulatory patients. Potassium-sparing diuretics are usually prescribed in combination with other preparations to prevent electrolyte disturbances. No randomized prospective large-scale trials have been carried out to compare the efficacy and tolerability of the various types of diuretics. With adequately chosen dosage, the effects of the different loop diuretics appear to be similar in CHF. However, observational data in ambulatory patient populations indicate that loop diuretics with high bioavailability and longer half-life may offer advantages in terms of clinical stability and resource utilization for cardiac decompensation. In patients with severe pulmonary congestion and oedema, combined use of loop diuretics and thiazides may improve the therapeutic response. Spironolactone can also be prescribed to increase diuresis in patients who are resistant to a combination of loop diuretics and ACE inhibitors.

Diuretics↗

Renal response to vasopressin after inhibition of prostaglandin synthesis.

The renal effects of vasopressin (VP) in water-loaded and hydropenic conscious dogs were examined with and without the previous administration of prostaglandin (PG) synthesis inhibitors (indomethacin and meclophenamate). The parameters studied were: urinary output, sodium and potassium excretion, plasma and urinary osmotic concentration, total renal blood flow, mean arterial pressure, heart rate, and the clearance and extraction ratio of p-aminohippuric acid and inulin. The infusion of VP caused antidiuresis and marked saluresis during water diuresis, whereas it was found to be diuretic and saluretic in hydropenic animals. Inhibition of PG synthesis greatly enhanced the antidiuretic activity of VP and abolished its saluretic and diuretic actions. Changes in renal water and solute excretion and changes in the hemodynamic parameters are uncorrelated. It is concluded that intrarenal PGs may play an important role in modulating the renal action of VP.

Animals↗

Induction of fetal diuresis with intraamniotic furosemide increases the clearance of intraamniotic substances: An alternative therapy aimed at reducing intraamniotic meconium concentration.

BACKGROUND/PURPOSE: Contact with amniotic fluid (AF) causes intestinal damage in gastroschisis. Intraamniotic meconium has been shown to be responsible for intestinal damage, and occurrence of this damage has been shown to depend on the concentration of intraamniotic meconium. When intraamniotic meconium concentration is lowered below threshold level by exchanging AF with saline in gastroschisis, intestinal damage can be prevented. Theoretically, induction of fetal diuresis with intraamniotic furosemide may increase AF volume and fetal swallowing rate, thus, increase absorption of AF by intestines; therefore, the clearance of meconium from the AF may increase. An experimental study was planned to investigate the effects of intraamniotic diuretic injection on the clearance of intraamniotic substances. METHODS: Pregnant rabbits on the 23rd to 25th gestational day were divided into 2 groups as furosemide and control. Technetium tc99m labeled "tin colloid" was injected into the amniotic cavity, and AF sample was taken 10 minutes later. Furosemide was injected into the amniotic cavity afterwards. Two and 6 hours later, AF samples were obtained. Intestines were harvested at the end of the study. Control group received intraamniotic saline instead of furosemide. Radioactivities of the AF samples and intestines were determined by gamma counter. Clearance of the radioisotope from AF and intestinal accumulation were calculated. RESULTS: The clearance of the radioisotope from AF was increased significantly in the furosemide group (n = 10) compared with the control group (n = 8; P <.01). Gastrointestinal accumulation of the radioisotope in the furosemide group was 4-fold higher than that the control group (P <.01). CONCLUSIONS: Induction of fetal diuresis with intraamniotic furosemide accelerates the clearance of intraamniotic substances. This is probably caused by increased urinary output rate, which increases AF volume and consequently results in increased fetal swallowing of AF. In the diseases like gastroschisis and myelomeningocele, in which the contact with AF causes tissue damage, the elimination of meconium from AF in a somewhat natural manner like this method, should be studied further because it may be an alternative minimal invasive in utero treatment modality.

Amniotic Fluid↗

The "well tempered" diuretic renogram: a standard method to examine the asymptomatic neonate with hydronephrosis or hydroureteronephrosis. A report from combined meetings of The Society for Fetal Urology and members of The Pediatric Nuclear Medicine Council--The Society of Nuclear Medicine.

Perinatal hydronephrosis (HN) and hydroureteronephrosis (HUN) are recognized more frequently as the routine use of prenatal ultrasonography increases. The decision-making process for those instances of urinary tract dilatation that require surgical correction and those that do not is based in part on the findings of diuresis renography. The methodology for performing this test has differed among nuclear medicine practitioners and the surgical findings are occasionally discrepant from the diuretic renogram interpretation. Consequently, the Society of Fetal Urology (SFU) and the Pediatric Nuclear Medicine Council (PNMC) of the Society of Nuclear Medicine met to develop by consensus a more uniform methodology. A standard method has been agreed upon for the following facets of diuretic renography: patient preparation (hydration and bladder catheterization), diuresis renography technique (radiopharmaceutical used, patient position during examination, data acquisition parameters, diuretic pharmaceutical and dosage, time of injection and regions of interest to monitor diuretic effect), and data analysis (percent differential renal function, curve pattern analysis and methods of measuring diuretic response). Pooled diuresis renogram data are being collected for analysis for correlation with surgical results and clinical outcomes to determine the most appropriate information to be derived from the diuretic renogram in neonates with HN and HUN.

Data Interpretation, Statistical↗

Pharmacokinetics and pharmacodynamics of bumetanide in neonates treated with extracorporeal membrane oxygenation.

Eleven term neonates treated with extracorporeal membrane oxygenation received bumetanide to treat volume overload. All patients had stable renal function, no history of prior diuretic therapy, and no overt evidence of hepatobiliary disease or hypoalbuminemia. Pretreatment creatinine clearance was 35.2 +/- 4.5 ml/min per 1.73 m2 (range, 20.3 to 57.5). Bumetanide, 0.095 +/- 0.003 mg/kg, was administered for 2 minutes into the postmembrane side of the extracorporeal membrane oxygenation circuit. Serial plasma and urine samples were collected for measurement of bumetanide and electrolyte concentrations. Total plasma and renal clearances for bumetanide were 0.63 +/- 0.11 and 0.16 +/- 0.04 ml/min per kilogram, respectively. The steady-state volume of distribution (0.44 +/- 0.03 L/kg) and the elimination half-life (13.2 +/- 3.8 hours) were greater than similar values reported in previous studies of bumetanide disposition in premature and term neonates who were not treated with extracorporeal membrane oxygenation. At observed rates of bumetanide excretion, the diuretic, natriuretic, and kaliuretic responses were linear. Significant diuresis, natriuresis, and kaliuresis were observed, although the duration of these effects was less than expected given the prolonged renal elimination of bumetanide. Nonrenal elimination of bumetanide was variable (47.2% to 96.9%) but higher than expected; this may explain the relatively brief diuretic and kaliuretic response.

Analysis of Variance↗

Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition.

BACKGROUND: Contrary to expectation, most studies have demonstrated that initiation of an angiotensin-converting enzyme (ACE) inhibitor in conventional doses in patients with heart failure reduces the diuretic efficacy of furosemide. Recently, it has been suggested that single low doses (1 mg) but not high doses (25 mg) of captopril enhance furosemide-induced diuresis. It is not known whether the interaction between diuretics and ACE inhibitors are altered during long-term dosing. METHODS AND RESULTS: Eight patients with heart failure treated with diuretics and ACE inhibitors for at least 3 months were studied. All patients were established on captopril 12.5 mg three times daily for 2 weeks before the study. Sodium intake was fixed before the study, and usual medication was withheld on study days. Intravenous furosemide was given on each of 2 study days to maintain a moderate, constant diuresis. Renal plasma flow and glomerular filtration rate (GFR) were determined using clearance techniques, and urine was collected hourly over 4 hours. Captopril 12.5 mg or placebo was given in a randomized, single-blind fashion at the end of the first hour. Compared with placebo, captopril reduced plasma concentrations of angiotensin II (23 +/- 18 versus 4 +/- 3 pg/ml 1 hour after dosing, P < .02) and systolic (131 +/- 31 versus 122 +/- 29 mm Hg, P < .01) and diastolic (74 +/- 15 versus 67 +/- 13 mm Hg, P < .05) blood pressures. GFR fell (55 +/- 24 versus 51 +/- 22 mL/min, P < .02) and effective renal plasma flow rose during the first (198 +/- 76 versus 231 +/- 49 mL/min) and second hours after dosing (185 +/- 69 versus 247 +/- 74 mL/min, P < .02). Similarly, urine volumes, in response to furosemide, increased after captopril (238 +/- 90 versus 283 +/- 111 mL, P < .05, and 245 +/- 78 versus 311 +/- 92 mL, P < .01, 1 and 2 hours after dosing). Urinary electrolyte concentrations fell, but total urinary sodium (22 +/- 7 versus 28 +/- 12 mmol/hr, P < .01) and chloride (20 +/- 6 versus 25 +/- 11 mmol/hr, P < .05) excretion increased in the 2 hours after dosing, as did fractional excretion of sodium (urinary sodium/urinary creatinine) (61 +/- 27 versus 75 +/- 36 mmol/mumol, P < .01). CONCLUSIONS: Intense although transient ACE inhibition with captopril enhances the diuretic effects of furosemide during long-term ACE inhibition.

Aged↗

Nocturnal diuresis in panhypopituitarism.

Although impaired water diuresis in adrenocortical insufficiency is well-known, little attention has been paid to the diuretic pattern at night. In two cases of panhypopituitarism, the nocturnal diuretic pattern was found to be quite different from that in the morning, and marked diuresis did occur after water loading at night, without any significant change of serum cortisol which remained at a low level throughout the day. At the antidiuretic stage in the morning, urine osmolality continued to rise gradually, in spite of the water loading, to the level of 666 mOsm/liter. At the water restriction test, the urine was concentrated only to the same level of 600-700mOsm/liter. At the ascending stage of urine osmolality, exogenously injected pitressin showed little antidiuretic effect, although the kidney was able concentrate urine to the higher level later. In the morning, 3 liters of 5% glucose infusion failed to produce a marked diuresis in spite of extreme plasma dilution and expansion. Furosemide immediately induced diuresis even in the morning and the kidney recovered its ability to respond to pitressin. Glucocorticoid also improved the diuretic pattern in the morning, but a latent period of about 2 hr was always observed before the appearance of the effect. What happened during this latent period was unclear, but it was interesting to note that a mechanism similar to that which induces diuretic response seemed to occur without glucocorticoid at night.

Betamethasone↗

Eukaliuric diuresis and natriuresis in response to the KATP channel blocker U37883A: micropuncture studies on the tubular site of action.

1. Systemic application of U37883A, a blocker of ATP sensitive potassium (KATP) channels, elicits diuresis and natriuresis without significantly altering urinary potassium excretion. 2. To elucidate tubular sites of action upstream to the distal nephron, micropuncture experiments were performed in nephrons with superficial glomeruli of anaesthetized Munich-Wistar-Frömter rats during systemic application of U37883A (1, 5 or 15 mg kg-1 i.v.). 3. The observed eukaliuric diuresis and natriuresis in response to U37883A at 15 mg kg-1 was accompanied by an increase in early distal tubular flow rate (VED) from 10 - 18 nl min(-1) reflecting a reduction in fractional reabsorption of fluid up to this site (FR-fluid) of 13%. The latter proposed an effect on water-permeable segments such as the proximal tubule which could fully account for the observed reduction in fractional reabsorption of Na+ up to the early distal tubule (FR-Na+) of 8% and the increase in early distal tubular Na+ concentration ([Na+]ED) from 35 - 51 mM whereas [K+]ED was left unaltered. 4. In comparison, furosemide (3 mg kg-1 i.v.), which acts in the water-impermeable thick ascending limb, elicited diuresis, natriuresis and kaliuresis which were associated with a fall in FR-Na+ of 10% with no change in FR-fluid, and a rise in [Na+]ED from 42 - 117 mM and [K+]ED from 1.2 - 5.7 mM with no change in VED. 5. Direct late proximal tubular fluid collections confirmed a significant inhibition of fluid reabsorption in proximal convoluted tubule in response to systemic application of U37883A. 6. These findings suggest that the diuretic and natriuretic effect upstream to the distal tubule in response to systemic application of U37883A involves actions on water-permeable segments such as the proximal convoluted tubule.

Adamantane↗

[Effect of amphotericin B on the diuretic action of diacarb and various indicators of water-salt metabolism in healthy and tumor-bearing animals].

The experiments with albino rats, Wistar rats and SHK mice showed that the combined use of amphotericin B and diacarb markedly potentiated the effect of the latter: the amount of the urine excreted within 6 h and the renal excretion of sodium ions increased 1.8 and 1.5 times, respectively. Analogous trends were observed in the experiments with stabilization of the animal water balance by 2 per cent water loading. The studies on rats with Pliss lymphosarcoma showed that the diuresis level in the tumor-bearing animals was 3 times lower than that in healthy rats. The treatment with 5-fluorouracil lowered this index more significantly. With the use of amphotericin B, diacarb and their combination the urination level came to normal. The cyclophosphamide therapy of mice with sarcoma 180 was accompanied by accumulation of water in the tumor tissue. The combined use of the cytostatic with the polyenic antibiotic and diuretic resulted in a significant lowering of this index. In rats with Walker-256 carcinosarcoma, the treatment with the above three drugs lowered the sodium ion concentration and increased the calcium ion concentration in the tumor tissue. At the same time the electrolyte level in some organs not affected with malignant tumor (spleen, thymus, liver and adrenal glands) returned to normal.

Acetazolamide↗

Solute-free versus electrolyte-free water clearance in the analysis of osmoregulation.

BACKGROUND: Although attention has recently focused on electrolyte-free water clearance (E-CH2O) as a replacement for solute-free water clearance (CH2O), especially from the viewpoint of plasma sodium regulation, a thorough comparison of the two has yet to be conducted. METHODS: CH2O and E-CH2O were systematically compared in normal subjects in different diuretic stages, including furosemide-induced solute diuresis, and in patients with renal disease. RESULTS: The normal renal ability to conserve free water based on E-CH2O was only 41% of that based on CH2O. E-CH2O remained positive until the urinary osmolality exceeded 500 mosm/kg H2O, markedly different from the 300 mosm/kg H2O for CH2O. The difference between E-CH2O and CH2O could ultimately be attributed to urea osmolar clearance, i.e., urea excretion rate/plasma osmolality, which accounted for about 40% of the osmolar clearance. CH2O underestimated the free water clearance by about 1 ml/min on average at all diuretic stages. CONCLUSIONS: E-CH2O is a more correct parameter than CH2O with regard to the regulation of both plasma sodium and plasma osmolality. However, there is the opinion that the concept of E-CH2O is difficult to understand and that E-CH2O is still not a generally accepted parameter. It is expected that the results of the present study will lead to more general acceptance.

Adult↗

Pharmacodynamic modeling of furosemide tolerance after multiple intravenous administration.

OBJECTIVE: Physiologic indirect-response models have been proposed to account for the pharmacodynamics of drugs with an indirect mechanism of action, such as furosemide. However, they have not been applied to tolerance development. The aim of this study was to investigate the development of tolerance after multiple intravenous dosing of furosemide in healthy volunteers. METHODS: Three repetitive doses of 30 mg furosemide were given as rapid intravenous infusions at 0, 4, and 8 hours to eight healthy volunteers. Urine samples were collected for a period up to 14 hours after the first dose. Volume and sodium losses were isovolumetrically replaced with an oral rehydration fluid. RESULTS: Tolerance was demonstrated as a significant decrease in diuretic and natriuretic response over time. Total mean diuresis was 35% lower (p < 0.01) and total mean natriuresis was 52% lower (p < 0.0001) after the third dose of furosemide compared with the first dose. However, there were considerable interindividual variations in the rate and extent of tolerance development for both diuresis and natriuresis. Pharmacokinetic-pharmacodynamic modeling of tolerance development was performed with use of an indirect-response model with an additional "modifier" compartment. This model gave an accurate description of the diuretic and natriuretic data after multiple dosing of furosemide and enabled the estimation of a lag-time for tolerance and a rate constant for tolerance development. Physiologic counteraction was demonstrated as a significant increase in plasma active renin levels (p < 0.00001) and a decrease in atrial natriuretic peptide levels (p < 0.005) during the day, concomitantly with the development of a negative sodium balance. This may be viewed as physiologic reflections of the modifier in our model. CONCLUSION: Indirect-response models may be successfully applied for tolerance modeling of drugs after multiple dosing.

Adult↗

Reversibility of diabetes- and diuresis-induced alterations in rat bladder dome muscarinic receptors.

Previous studies from our laboratory demonstrated that 8 weeks of streptozocin (STZ)-induced diabetes and sucrose-fed diuresis resulted in increases in the density of muscarinic receptors in rat bladder dome and that early insulin treatment (started 3 days after the onset of diabetes) prevented the diabetes-induced upregulation (J Pharmacol Exp Ther 248:81-88, 1989; Diabetes 40: 1150-1156, 1991; J Urol 147:760-763, 1992). To determine whether diabetes- and diuresis-induced alterations in muscarinic receptors in rat bladder dome are reversible, we administered insulin (beginning 8 weeks after the onset of diabetes) or removed sucrose from drinking water of diuretic rats (beginning 8 weeks after the onset of diuresis). Five groups of rats were maintained for 16 weeks: 1) STZ-induced diabetic rats (65 mg/kg intravenously); 2) insulin-treated diabetic rats (5-8 U/day insulin subcutaneously beginning 8 weeks after the onset of diabetes); 3) sucrose-fed diuretic rats (5% sucrose in drinking water throughout 16 weeks); 4) sucrose-removed rats (sucrose withdrawn from drinking water after 8 weeks of the sucrose-induced diuretic state); and 5) age-matched control rats. Radioligand receptor binding experiments with [3H]quinuclidinyl benzilate showed an increase in the density of muscarinic receptors in bladder dome of diabetic and sucrose-fed rats compared with age-matched control rats. Removing the 5% sucrose from the drinking water of diuretic rats reversed the increased water intake and urine output, decreased the bladder hypertrophy that accompanied the diuretic state, and corrected the upregulation of the muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of diuresis on extracorporeal shockwave lithotripsy treatment of ureteric calculi.

OBJECTIVE: To evaluate the effect of diuresis during extracorporeal shockwave lithotripsy (ESWL) treatment of ureteric calculi. The purpose is to improve stone fragmentation and clearance rates. MATERIALS AND METHODS: One hundred and six consecutive patients with ureteric calculi at different levels were treated by ESWL using Siemens Lithostar 2 machine. Patients have been randomized into two treatment groups. The first group was treated by standard ESWL and included 54 patients. The second group was treated by ESWL with diuresis during the ESWL session. Shock waves were given at a rate of 90 shocks/minute with energy starting from 10 up to 18 KV. During the ESWL session the patient belonging to the second group received i.v. infusion of 500 ml normal saline containing 40 mg furosemide as a diuretic. The stone fragmentation and clearance rates were the two end points for evaluation. RESULTS: The average number of sessions per stone was 1.92 and 1.5 and the average number of shocks per stone was 6295 and 5300 for the first and second treatment groups respectively. Stone fragmentation rate was 47/54 (87%) and 50/52 (96.2%) and the stone clearance (success) rate was 47/54 (87%) and 48/52 (92.3%) for the first and the second groups respectively. Analysis of the results in relation to stone location showed that the two treatment groups were comparable for upper and middle ureteric calculi. However for distal ureteric stones, the addition of diuresis during ESWL was associated with a lower mean number of ESWL sessions and shocks per stone compared with standard ESWL: 1.38 and 4950 for ESWL with diuresis compared with 2.9 and 8544 for standard ESWL respectively. The stone fragmentation and 3-month clearance (success) rates were clearly higher: 93.8% and 87.5% respectively for ESWL with diuresis compared with 70.6% (for both fragmentation and clearance) with standard ESWL. CONCLUSIONS: Diuresis is a useful, inexpensive and safe adjunct to ESWL of ureteric stones. It markedly improves the results of ESWL treatment of distal ureteric stones compared with standard ESWL.

Adolescent↗

The role of renal nerves in the diuresis and natriuresis 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 in anaesthetized dogs in which on kidney had been surgically denervated. In these dogs diuretic and natriuretic responses to stimulation of atrial receptors were obtained in the denervated and the intact kidney; both responses were significantly greater in the intact kidney than in the denervated kidney. In the denervated kidney the natriuretic response showed a significant correlation to increases in heart rate resulting from stimulating of atrial receptors. It is concluded that the renal nerves contribute significantly to the increases in urine flow and sodium excretion in response to stimulation of atrial receptors. In the denervated kidney, the diuresis appeared to be mediated by a humoral mechanism and the natriuresis was associated with concomitant increases in heart rate.

Animals↗

Diuretic renography and angiotensin converting enzyme inhibitor renography.

Renovascular hypertension and renal outlet obstruction are two clinical conditions well evaluated by nuclear medicine techniques. They both require a specific intervention to challenge a specific aspect of renal functional reserve. Diuretic renography is the oldest common example in nuclear medicine where functional change in the kidney is provoked for diagnostic purposes. The kidney's tubular functional reserve, in this instance, is challenged to induce diuresis and increase urine flow. This intervention permits diuretic renography to retain an essential role in the evaluation of hydroureteronephrosis. Captopril renography is a more recent example of a similar principle and depends on a reactive renin-angiotensin system to identify a kidney responsible for RVH. In both renal outlet obstruction and RVH, an anatomic abnormality is also identified (hydronephrosis and RAS, respectively) at some point in the diagnostic workup. The final diagnosis in each instance, however, depends on evidence for a functional disorder, provoked and measured during the radionuclide interventional examination. These serve as excellent examples of the power of functional imaging to identify specific medical disorders.

Angiotensin-Converting Enzyme Inhibitors↗

Potent potentiating diuretic effects of prednisone in congestive heart failure.

UNLABELLED: Animal studies showed glucocorticoids could specifically dilate renal vasculature, regulate synthesis and release of atrial natriuretic peptide (ANP), upregulate ANP receptors on vascular endothelial cells, and thus have potent potentiating diuresis and natriuresis effects in animal studies; however, their diuretic efficacy in humans is yet to be known. Therefore, we designed this randomized, double- blind, placebo-controlled, clinical study to determine the diuretic efficacy of prednisone, a glucocorticoid, in patients with congestive heart failure (CHF). METHODS: Twenty clinically stable patients with CHF without overt fluid retention were randomized to a prednisone group or placebo group. Prednisone (1 mg/kg/day with a maximum dose of 60 mg/day) was added to standard care for 7 days, leaving other medications unchanged. Variables included urine volume and electrolytes, serum electrolytes, and change from baseline in serum creatinine. RESULTS: Adding prednisone resulted in striking diuresis and natriuresis with time. As compared with the placebo group, the maximum of mean daily urine volume was 810.5 mL larger than those in the placebo group (95% confidence intervals [CI] 276.25 to 1344.86, P < 0.05). The maximum mean daily sodium excretion was 123.8 mmol higher than those patients given placebo (95% CI 11.4 to 236.2, P < 0.05). The placebo-corrected effect on change from baseline in serum creatinine was -19.5 mumol/L (95% CI -7.4 to -31.6, P < 0.01), favoring prednisone. CONCLUSIONS: This pilot study showed that prednisone had potent potentiating diuretic effects in patients with heart failure and might improve renal function in the same time. Further prospective randomized clinical studies are warranted to determine the preferable dose and its efficacy in decompensated congestive heart failure.

Adult↗

The renal kallikrein-kinin system in spontaneously hypertensive rats.

In male spontaneously hypertensive rats (SHRSP) of the stroke prone strain (Okamoto) and in normotensive Wistar-Kyoto rats (WKY) urinary kallikrein excretion was investigated at different age and at drug-induced diuresis. In rats of both strains from 7th till 19th week of age urinary kallikrein excretion increased with age. In SHRSP of 7th till 11th week of age kallikrein excretion was higher than in WKY rats, while it was lower in the 48-week-old SHRSP. No correlation was found between urinary kallikrein excretion and systolic blood pressure. In SHRSP and WKY rats a similar daily rhythm of kallikrein excretion in urine was found being high in the early morning and low in the afternoon. Kallikrein excretion correlated significantly with urine volume. The loop diuretic bumetanide (4 and 40 mg/kg) induced diuresis and natriuresis in both strains, however more marked in the WKY rats than in the SHRSP. Urinary kallikrein excretion, however, showed in both strains the same biphasic course with a short lasting increase and a secondary decrease. Thus, in the average urinary kallikrein excretion was not effected by the drug. Prolonged treatment with furosemide over 5 days (125 mg/kg) resulted in an increase in kallikrein excretion in urine, more pronounced in the WKY rats than in the SHRSP. The observed results suggest that renal kallikrein-kinin system is not involved in the development of spontaneous hypertension as a pathogenetic factor, but rather is influenced by other factors like hormone interactions, i.e. mineralocorticoids and catecholamines, as well as renal function and acute changes in urine flow.

Angiotensin II↗