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Serum lipoproteins and indices of glucose tolerance during diuretic therapy: a comparison between hydrochlorothiazide and piretanide.

Two diuretic drugs, hydrochlorothiazide (HCT) and piretanide (PT), were compared for their effects on plasma lipoproteins and glucose tolerance in 24 hypertensive male subjects over a period of 12 weeks. In comparison with preceding placebos, both drugs caused an increase of total cholesterol, low-density lipoprotein (LDL) cholesterol, total triglyceride, and very-low-density lipoprotein (VLDL) triglyceride concentrations, whereas no significant change occurred in high-density lipoprotein (HDL) cholesterol. The alterations were partly reversible in patients receiving HCT. Apoprotein A and B concentrations were increased by PT but were little influenced by HCT. Also, the LDL/HDL cholesterol ratio was increased during PT. Neither drug invariably influenced the postheparin plasma lipase activities, oral glucose tolerance, plasma insulin levels, or insulin binding to red cells. The results suggest that diuretic drugs may promote the hepatic secretion of VLDL. The mechanism of this action remains to be established, and the clinical relevance of these findings is still not clearly understood.

Adult↗

Blood pressure variability in ambulatory hypertensive patients: effect of beta-blocking agents and/or diuretics.

Using a semiautomatic device (Remler), ambulatory blood pressure was recorded in ambulatory hypertensive patients who were either untreated (n = 55) or treated chronically with beta-blocking agents (n = 28), diuretics (n = 42), or a combination of both (n = 75). In all patients, one blood pressure reading was obtained during usual activities every 30 min for 12 h. The selection of untreated patients was based on clinic measurements (two to three repeated blood pressures of greater than 140/89 mm Hg). The mean systolic and diastolic blood pressures averaged from all patients over the whole day did not differ significantly among the groups, ranging from 133.7 to 141 mm Hg for the systolic and from 83.8 to 88.4 mm Hg for the diastolic. The variability of blood pressure, reflected by the difference between the average of the three highest and the three lowest values of the day, was not different among the four groups and ranged from 41.4 to 50.6 mm Hg for the systolic and from 30.1 to 34.4 mm Hg for the diastolic. Similarly, variability expressed as the standard deviation of the mean of all blood pressures measured during the day did not differ among the groups. In all groups, blood pressure was highest in the morning and lowest in early afternoon, and tended to rise again in the late afternoon. Thus, blood pressure variability of hypertensive patients is not changed by antihypertensive therapy with beta-blocking agents and/or diuretics.

Adrenergic beta-Antagonists↗

CE inhibition and natriuresis with ramipril in conscious SHR: different modes of action of loop and thiazide diuretics.

Acute effects of piretanide, a loop diuretic, on blood pressure (BP) and urinary output as well as long-term effects on serum electrolytes were compared in conscious spontaneously hypertensive rats (SHR) to that of hydrochlorothiazide (HCT) both given alone and in combination with the converting enzyme (CE) inhibitor ramipril. There were no acute or chronic falls in BP with low doses of either diuretic. Ramipril at a dose of 10 mg/kg normalized BP, which was accompanied by initial natriuresis and, over the long term, K+ preservation. Minimally effective doses of piretanide but not HCT given in combination with 1 mg/kg ramipril produced a greater fall in BP both acutely and chronically than ramipril alone at unaltered K+ preservation. To match this fall in BP with HCT, large doses were required, which caused hemoconcentration and impaired K+ preservation.

Angiotensin-Converting Enzyme Inhibitors↗

First-line treatment of left ventricular failure complicating acute myocardial infarction: a randomised evaluation of immediate effects of diuretic, venodilator, arteriodilator, and positive inotropic drugs on left ventricular function.

A prospective randomised trial compared the immediate haemodynamic effects of intravenous diuretic (frusemide), venodilator (isosorbide dinitrate), arteriolar dilator (hydralazine), and positive inotropic stimulation (prenalterol) as first-line therapy for acute left ventricular (LV) failure following myocardial infarction. Forty-eight patients with transmural myocardial infarction and a pulmonary artery occluded pressure (PAOP) of greater than 20 mm Hg were studied within 18 h of admission to a coronary care unit. Both frusemide (-4 mm Hg; p less than 0.01) and isosorbide dinitrate (-6 mm Hg; p less than 0.01) reduced LV filling pressure without change in cardiac index and heart rate. Although both hydralazine and prenalterol increased cardiac index (p less than 0.01), the reduction in LV filling pressure (-2 mm Hg; p less than 0.05) was less than with frusemide and isosorbide dinitrate, and was associated with an increased heart rate (+8 and +13 beats min-1; p less than 0.01). These data suggest that in acute heart failure following myocardial infarction the four treatment modalities could be ranked in descending order of potential benefit as follows: venodilatation (isosorbide dinitrate)--decrease of LV pressure/work; diuretic therapy (frusemide)--decrease of LV pressure/work offset by a transient pressor effect; arteriolar dilatation (hydralazine)--decrease of LV pressure/work and of PAOP, but offset by tachycardia; and positive inotropic therapy (beta 1-agonist prenalterol)--tachycardia and augmented LV afterload. Combination of the former and latter agents, because of their differing modes of action, should offer haemodynamic advantages over monotherapy and deserves further evaluation.

Adult↗

Diuretic effect of nitrendipine contributes to its antihypertensive efficacy: a review.

The mechanism of the antihypertensive effect of nitrendipine is believed to be vasodilation, resulting in a reduction of the total peripheral resistance. However, in contrast to other arteriolar vasodilators, nitrendipine exerts natriuretic and diuretic effects that are more pronounced in hypertensive than in normotensive rats. In rat kidneys, nitrendipine caused a complete reversal of the decrease of glomerular filtration rate (GFR) induced by norepinephrine or angiotensin II, probably due to a selective antagonism of preglomerular vasoconstriction. A selective dilation of afferent arterioles was shown in microcirculatory studies on hydronephrotic kidneys. In normotensive rats with intact kidneys, nitrendipine increases natriuresis by inhibition of sodium reabsorption, presumably in the proximal tubuli. In normotensive humans, natriuresis was enhanced also by a primary tubular effect of nitrendipine. In hypertensive patients, an initial increase in GFR was observed; a persistent diuretic effect under chronic treatment was due to a tubular action. In spontaneously hypertensive rats (SHR), chronic treatment with nitrendipine resulted in a regression of cardiac hypertrophy in parallel with a reduction of plasma levels of atrial natriuretic peptides (ANPs), probably due to the persistent natriuretic effect. Treatment with minoxidil resulted in fluid retention, increase in ANP levels, and aggravation of cardiac hypertrophy.

Animals↗

The diurnal rhythm of plasma potassium: relationship to diuretic therapy.

Plasma potassium levels have been implicated in the genesis of cardiac arrhythmias, particularly in patients receiving diuretic therapy. The present study was undertaken to evaluate the stability of plasma potassium levels throughout a 28-h period. Normal volunteers (n = 8) and subjects with essential hypertension (n = 10) were studied in a clinical research center while receiving controlled dietary intakes. Plasma potassium followed a diurnal rhythm in both groups, with a peak level at 12 h and a trough level at 24 h. The average peak-to-trough difference was 0.62 +/- 0.05 mmol/L. Urinary potassium excretion also followed a diurnal rhythm, with the lowest excretory rate during the evening hours, when plasma potassium reached its nadir. Subjects with essential hypertension were restudied after 4 weeks of hydrochlorothiazide (50 mg/day) and then after an additional 4 weeks of hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day). Hydrochlorothiazide alone reduced plasma potassium at all times of measurement without altering the diurnal rhythm. The combination of hydrochlorothiazide and amiloride resulted in higher plasma potassium levels in the morning, but did not significantly affect evening plasma potassium levels. The frequency of hypokalemia (K less than or equal to 3.0 mmol/L) was related to the time at which the plasma potassium was measured. We conclude that plasma potassium undergoes a diurnal rhythm and that diuretics shift this rhythm to uniformly lower values. This rhythm must be considered when defining the frequency of hypokalemia.

Adult↗

Loop diuretic therapy in acute and chronic renal failure.

The development of the powerful loop diuretics over the past 30 years has significantly improved the quality of life for patients with advanced chronic renal failure (CRF). The most recent of these drugs is torasemide. This review outlines its mode of action and its pharmacokinetics and pharmacodynamics in CRF. A personal view of the efficacy and usefulness of these drugs in CRF, CRF on dialysis, and in nephrotic syndrome is given. The role of loop diuretics in potential and/or established acute renal failure is unknown. Theoretical advantages are described, current knowledge reviewed, and an outline of a prospective study presently underway is given.

Acute Kidney Injury↗

The natural history of nephrocalcinosis in premature infants treated with loop diuretics.

PURPOSE: We investigated the natural history of nephrocalcinosis in premature infants treated with furosemide and attempted to identify factors to predict infants most at risk. MATERIALS AND METHODS: We evaluated 13 preterm infants in this longitudinal pilot study. During hospitalization and while receiving a loop diuretic nephrocalcinosis developed in each patient. Patients were divided into groups based on resolution (6) and nonresolution (7) according to spontaneous resolution of nephrocalcinosis at any point during followup. The 2 groups were compared to each other and to a control group. RESULTS: Mean followup after discontinuation of furosemide in the resolution versus nonresolution groups was 10.3 and 7.7 months, respectively. Between the 2 groups there was no significant difference in average gestational age, birth weight, number of days hospitalized or on furosemide, or total furosemide dose. Mean calcium-to-creatinine ratio while receiving furosemide at the time nephrocalcinosis developed was 0.38 in the resolution group but 2.23 in the nonresolution group (p < 0.005). Initial calcium-to-creatinine ratio in age matched infants who did not have nephrocalcinosis was 0.4. Frank renal stones developed in 2 of the 7 patients without resolution and 0 of the 6 with resolution. When nephrocalcinosis resolved, it was at a mean of 5.2 months following discontinuation of the diuretic. CONCLUSIONS: Early data indicate that nephrocalcinosis resolves in approximately 50% of premature infants 5 to 6 months after discontinuation of furosemide. The only factor that appears to be predictive of the infants who will have resolution is the calcium-to-creatinine ratio when nephrocalcinosis is diagnosed. In patients without resolution this ratio is much higher than in age adjusted normal controls, while in those with resolution it appears normal for age.

Diuretics↗

The 99mTc-DMSA renal scan and 99mTc-DTPA diuretic renogram in children and adolescents with incidental diagnosis of horseshoe kidney.

A prospective study was conducted to determine the possibility of obstructive hydronephrosis in horseshoe kidney found incidentally in school children and adolescents by using a radionuclide diuretic renogram. In a 2-year period, 22 school children and adolescents with horseshoe kidney were found in a mass renal sonography survey. They each underwent a 99mTc dimercaptosuccinic acid renal cortical scan to confirm the horseshoe kidney. Each diuretic renogram was performed with the patient in the supine position to rule out obstructive hydronephrosis. The patients were advised to empty their bladders before the intravenous injection of furosemide (1 mg x kg(-1)). The half-time for the clearance of radioactivity from the renal pelvis were calculated. Of the 22 patients, asymmetrical renal cortical function between the two kidneys was found in 14 (63.6%). Eleven kidneys (11/44, 25%) showed stasis of radioactive urine in the renal pelvic region prior to injection of furosemide. There was no incidence of bilateral hydronephrosis in these 22 patients. Only one kidney (1/44, 2.3%) showed obstructive hydronephrosis and five showed clearance of radioactive urine stasis from the renal pelvis immediately after standing up for voiding. There is a low percentage of obstructive hydronephrosis in these cases of horseshoe kidney found incidentally in children and adolescents. A follow-up cohort study on these patients would be valuable for monitoring the development of complications.

Adolescent↗

Combined use of lithium and diuretics.

Three cases demonstrating the effects of the combined use of lithium carbonate and a diuretic are reported. In each case, the serum lithium level rose, or the daily dose was decreased, or both. No clinical problems were noted because of careful monitoring and patient education. The renal excretion of lithium is reviewed. It is concluded that lithium and diuretics is a safe drug combination, if it is necessary to give both drugs.

Aged↗

Hyperglycemia and diabetic coma: possible relationship to diuretic-propranolol therapy.

Two patients developed diabetic coma when taking a combination of a thiazide diuretic and propranolol. On subsequent follow-up one patient is taking no insulin and has been maintained on hydrochlorothiazide; the other patient required insulin on two occasions when challenged with a propranolol-thiazide combination, but not when the thiazide was discontinued or replaced with furosemide. These reports suggest the possibility that the risk of developing hyperglycemia and diabetic coma with this combination may be greater than when taking diuretics alone. The mechanism is probably multifactorial.

Diabetic Coma↗

Hyponatremia induced by thiazide-like diuretics in the elderly.

We have presented five episodes of hydrochlorothiazide-induced hyponatremia in three elderly nursing home patients. Fortunately all our patients survived. The common use of thiazide diuretics in this population and the nonspecific symptoms that follow toxicity make it imperative to monitor closely elderly patients who are taking thiazide diuretics.

Aged↗

Hyperkalaemia and diarrhoea in a patient with surreptitious ingestion of potassium sparing diuretics.

We report a patient who presented with the unusual combination of chronic diarrhoea and hyperkalaemia. The patient was admitted to our hospital after repeated negative evaluations elsewhere including exploratory laparotomy. The patient had a long history of diarrhoea with hypokalaemia which was documented on several occasions in the past. Several months before admission to our hospital for evaluation of diarrhoea the patient developed hyperkalaemia. Her daily stool output reached 1200 g and her serum potassium was as high as 6.0 mmol/l. Extensive evaluation revealed surreptitious ingestion of the diuretics triamterene, hydrochlorothiazide and spironolactone as the cause of hyperkalaemia and diarrhoea. In addition, she had melanosis coli which was interpreted to be the consequence of surreptitious ingestion of anthraquinone-containing laxatives in the past although no current laxative intake could be proven. We postulate that diarrhoea in our patient was mainly due to the decreased sodium absorption in the small intestine and colon caused by diuretics. Serum aldosterone levels were more than eight times the upper limit of normal. Increased aldosterone levels presumably arose secondary to volume contraction and sodium chloride depletion, but presumably were not able to affect renal and colonic electrolyte transport because of blockage of mineralocorticoid receptors by spironolactone. Thus, the unusual combination of diarrhoea and hyperkalaemia resulted.

Chronic Disease↗

Furosemide: progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases.

Accumulated experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in the mechanism of furosemide diuretic action. It was reported that the drug is highly bound in the adrenals, lungs, kidney, spleen, and liver. In patients with liver cirrhosis, furosemide exerted a markedly decreased natriuretic effect compared with normal subjects, and the plasma levels of circulating endothelin and atrial natriuretic factor (ANF) were significantly elevated. In neonates, after administration of furosemide, the urinary excretion of endothelin-1 and aldosterone increased markedly, and it is known that endothelin may release ANF and aldosterone in a dose-dependent manner. Furosemide was used to stimulate zona glomerulosa, whereas ANF decreased the production of steroids in zona glomerulosa and fasciculata cell culture owing to stimulation by various factors. Because the concomitant use of ANF and furosemide appeared to be diuretically effective in newborns after cardiac surgery, one may suggest that furosemide competes with ANF for its effects on the adrenals. Furosemide administered by inhalation exerted a protective effect on allergic and perennial nonallergic rhinitis and was effective in preventing the postsurgical recurrence of nasal polyposis. The drug can also be used as an antiasthmatic agent. In preterm ventilator-dependent infants with chronic lung disease, aerosolized furosemide improved pulmonary function with no marked effect on diuresis. In adults and children with asthma, furosemide exerted a protective effect against bronchoconstriction induced by several indirect stimuli similar to that of disodium cromoglycate or nedocromil. Aerosolized furosemide had a preventive effect also on bronchoconstriction induced by inhaled lysine acetylsalicylate in patients with aspirin-sensitive asthma. In high-dose beclomethasone-dependent asthma, inhaled lysine acetylsalicylate and furosemide exerted a mutually potentiating antiasthmatic activity, allowing considerable sparing of the inhaled steroid. It is proposed that this effect may be explained by the corticosteroid-sparing action of lysine released from the lysine acetylsalicylate molecule because similar beneficial effects were also obtained after the concomitant use of epsilon-aminocaproic acid (whose chemical structure is almost the same as that of lysine) and prednisone. Furosemide exhibited an anti-inflammatory effect through inhibition of production and release of cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha from peripheral mononuclear cells, which may have a beneficial effect on local inflamed tissue imbalance in the ratio of different cytokines, thus improving the sensitivity of target cells to endogenous glucocorticosteroids.

Adult↗

Diuretic treatment of nocturnal enuresis: preliminary results of an open pilot study.

PURPOSE: Since antidiuretic treatment with desmopressin in the evening has proven effective against enuresis, it would not be surprising if diuretic treatment in the afternoon would have similar effects. We are currently testing this in an open pilot investigation. MATERIALS AND METHODS: A total of 33 children including 12 girls with a mean age +/-SD of 7.6 +/- 2.3 years with monosymptomatic enuresis were recruited from an outpatient primary care setting. Wet and dry nights were recorded for 2 weeks without medication, 2 weeks with 0.4 mg desmopressin orally at night and 2 weeks with 1 mg/kg furosemide 4 to 5 hours before bedtime. RESULTS: The mean number of wet nights +/-SD during the 3 periods was 10.2 +/- 3.0, 6.7 +/- 4.7 and 7.8 +/- 4.5, respectively. The effects of desmopressin and of furosemide were statistically significant (p <0.0001 and p = 0.001), although the 2 treatments did not differ (p = 0.08). Only 6 children had a complete response (ie greater than 90% reduction in wet nights) to desmopressin and 5 responded to furosemide. Interestingly, 2 children had a clearly better response on furosemide than on desmopressin. CONCLUSIONS: The treatment of enuresis with diuretic medication in the afternoon may be beneficial but needs to be tested in randomized controlled trials.

Adolescent↗

Diuretic renogram clearance half-times in the diagnosis of obstructive uropathy: effect of age and previous surgery.

Diuretic renography with radiotracers has been used successfully to diagnose obstruction in patients with hydronephrosis. Controversy persists with regard to the best approach for the interpretation of renogram curves: visual analysis or a quantitative index, i.e. the clearance half-time. The latter is often reported to be in the intermediate or non-diagnostic range. It is important to measure the incidence of equivocal half-times in various subsets of patients with hydronephrosis in order to determine in which settings the measurement of this index may be clinically useful. We performed a retrospective study of diuretic renograms performed at our institution between 1997 and 2000 for the evaluation of suspected uretero-pelvic junction (UPJ) obstruction. Vigorous intravenous hydration, exceeding current guidelines, was employed in these patients. Three hundred and seventy-seven renogram curves in 205 patients were analysed. Patients were divided into three groups: >1 year of age; 20 min) or intermediate (half-time, 10-20 min). In patients >1 year of age, 37% of 101 renograms showed normal half-times before furosemide, 20% showed normal half-times after furosemide, 44% showed prolonged half-times and none (0%) showed an intermediate half-time. In patients </=1 year of age, there was a statistically significantly different distribution, with 48% of 64 renograms showing normal washout before furosemide, 16% showing normal clearance after furosemide, 19% showing abnormal half-times and 17% showing intermediate half-times. In 33 renograms from patients who had undergone corrective surgery, 49% had normal half-times, 24% had prolonged half-times and 27% had intermediate half-times. It can be concluded that, when using the selection criteria, hydration, acquisition and processing protocols and half-time definition employed in this study, the addition of a clearance measurement in patients older than 1 year with suspected UPJ disease enhances patient classification and may improve the diagnostic confidence. There was a significantly higher incidence of intermediate half-times in patients with native disease aged <1 year than in those >1 year. Caution is advised when interpreting this finding in this age group. The measurement of washout was less useful in patients who had undergone a corrective procedure, because of the high rate of 'indeterminate' and 'abnormal' values in spite of successful surgery. Vigorous intravenous hydration, exceeding current standards, may have contributed to the lower incidence of intermediate half-times than reported previously.

Adolescent↗

Comparison of three different diuretic renal scintigraphy protocols in patients with dilated upper urinary tracts.

PURPOSE: To compare 3 different diuretic renal scintigraphy protocols in patients with dilated upper urinary tract. MATERIALS AND METHODS: Three diuresis renography protocols were performed in 22 adult patients (28 kidneys) with upper urinary tract dilatation. The diuretic was given 20 minutes after (F+20), at the same time as (F+0), and 15 minutes before (F-15) radionuclide administration. The mean age was 29.8 years (range, 18-43 years). The 3 protocols were identical, except for the time of injection of furosemide. The F+0 protocol could not be performed in 1 and F-15 in 2 of the patients. Each of the 3 protocols was performed for the rest of the patients. The results were classified as nonobstructive, equivocal, and obstructive according to the renogram images and curves. RESULTS: None of the patients showed equivocal results in both F+0 and F-15 protocols. In the F+20 studies, 7 of the 28 kidneys were evaluated as equivocal. Of these, 5 kidneys showed nonobstructive and 2 kidneys revealed obstructive renogram patterns with the other 2 protocols (F+0 and F-15). Moreover, one kidney, which was evaluated as nonobstructive in the F+20 protocol, showed an obstructive pattern in both F+0 and F-15 protocols. All of the kidneys showing obstructive patterns in the F+20 study also revealed obstruction in the F+0 and F-15 investigations. We could not find any difference between the renogram patterns of F+0 and F-15 investigations. CONCLUSIONS: F+0 and F-15 protocols allow clarification in cases of equivocal F+20 studies. Because the F+0 study is more practical and shorter, we suggest the F+0 method when equivocal results are obtained by an F+20 study or as a single test when there is only one opportunity to confirm or exclude the presence of obstruction.

Adolescent↗

Treatment of diuretic-resistant fluid retention with ultrafiltration.

Nine patients with diuretic-resistant edema, secondary to congestive heart failure, liver cirrhosis, or nephrotic syndrome, were treated with ultrafiltration using high water flux dialyzers. Access to the blood stream was obtained by femoral vein catheterization. As much as 8.3 kg of fluid were removed in 3--4 hours with only transient decline in blood pressure. The procedure was well tolerated and yielded immediate symptomatic relief. The potential for restoration of an edema-free state in patients with diuretic-resistant edema suggests that further experience with this technique is justified.

Diuretics↗