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PubMed1992

Diabetes, impaired glucose tolerance and insulin resistance with diuretics.

There is a definite relation of diuretic treatment to impaired glucose tolerance and biochemical diabetes, and a probable relation to insulin resistance. The effect of diuretics on glucose tolerance is dose-related. Spironolactone does not impair glucose tolerance even at high dosage, but apparent differences between other diuretics may well be due to comparison at doses which are not equivalent. Diuretic-induced changes in carbohydrate metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs when relatively low doses of thiazide are combined with potassium-sparing agents. The effect of diuretics on glucose tolerance is largely and possibly wholly reversible. These disturbances of carbohydrate homeostasis have been detected by detailed biochemical testing, and their clinical importance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In non-diabetic subjects diuretics may rarely cause or trigger a serious hyperosmolar non-ketotic diabetic syndrome. This apart, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long-term. It is now established that biochemical diabetes, glucose intolerance and insulin resistance probably do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes, otherwise they remain an excellent choice for first-line antihypertensive therapy.

Blood Glucose↗
PubMed2000

Older age and in-hospital development of hypokalemia from loop diuretics: results from a multicenter survey. GIFA Investigators. Multicenter Italian Pharmacoepidemiologic Study Group.

BACKGROUND: Hypokalemia is a common finding among older patients taking diuretic medications. However, it is not known whether older age per se carries an increased risk of hypokalemia, particularly during a patient's treatment with loop diuretics. METHODS: The association between age and incident hypokalemia was examined in 18,872 patients with normal baseline serum potassium enrolled during three yearly multicenter surveys; 4,035 patients started receiving loop diuretics during their hospital stay. Demographic variables, comorbid conditions, medications, and objective tests that were associated with incident hypokalemia in separate age- and sex-adjusted logistic regression models were examined as potential confounders. RESULTS: Among patients with normal baseline serum potassium, the factors of age, presence of coronary disease or diabetes, comorbidity, the use of ACE inhibitors, loop diuretics, digitalis, corticosteroids, or insulin, and baseline serum potassium were associated with incident hypokalemia in initial models. After these variables were adjusted for, age (for each decade, odds ratio = 1.30; 95% confidence interval = 1.17-1.46; p < .0001) was associated with incident hypokalemia. The use of parenteral (2.30; 1.53-3.46; p < .0001) but not oral (1.16; 0.79-1.69; p = .44) loop diuretics was associated with hypokalemia. Eventually, age was associated with hypokalemia when the summary regression model was analyzed in patients taking loop diuretics (1.33; 1.03-1.71; p = .027), as well as in those taking intravenous loop diuretics only (1.84; 1.25-2.70; p = .002). CONCLUSIONS: Older age is independently associated with the in-hospital development of hypokalemia, particularly among patients taking loop diuretics. Monitoring of serum potassium levels is therefore advisable when older patients are treated with these agents.

Age Factors↗
PubMed1985

Clinical effects of low-dose captopril plus a thiazide diuretic on mild to moderate essential hypertension: a multicenter double-blind comparison with propranolol. Captopril Research Group of Japan.

A total of 270 patients with mild to moderate essential hypertension were evaluated in a multicenter double-blind randomized study that compared the effect of captopril plus a thiazide diuretic with that of propranolol plus a diuretic. All patients were previously uncontrolled with diuretics alone. Following a 4-week placebo control period, during which diuretic was not withdrawn, the patients were treated either with 37.5-75 mg/day of captopril (n = 133) or with 60-120 mg/day of propranolol (n = 137) for 12 weeks, the diuretic being continued in both groups. Blood pressure in both groups was significantly reduced after 2 weeks of treatment. Reduction in systolic but not diastolic blood pressure after 10 and 12 weeks of treatment was significantly greater in the captopril group than in the propranolol group (p less than 0.05). Treatment was considered to be effective in 77% of the captopril patients and in 61% of the propranolol group. The difference was significant (p less than 0.05). Side effects occurred in 6 of the 133 patients (4.5%) treated with captopril and in 16 of the 137 patients (11.7%) treated with propranolol. The difference between the two groups was significant (p less than 0.05). There were few significant changes in laboratory data in either group. The serious side effects previously reported with higher doses of captopril were not observed. The results indicate that low-dose captopril plus a diuretic is more efficacious than propranolol plus a diuretic in mild to moderate essential hypertension previously uncontrolled with a diuretic alone.

Adult↗
PubMed1999

Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations.

BACKGROUND: The effects of chronic diuretic use on serum homocysteine and its metabolic cofactors vitamin B6, vitamin B12, and red blood cell (RBC) folate have not been well studied. METHODS: Blood samples from 17 hypertensive patients receiving long-term diuretic therapy and 17 hypertensive patients not taking diuretics were analyzed for serum homocysteine, vitamin B6, vitamin B12, and RBC folate. RESULTS: The mean serum homocysteine concentration for patients taking diuretics (17.87 +/- 1.72 micromol/L) was significantly higher than the mean serum homocysteine concentration for patients not taking diuretics (10.31 +/- 0.99 micromol/L). The mean RBC folate concentration for patients taking diuretics (281.01 +/- 17.56 ng/mL) was significantly lower than the mean RBC folate concentration for patients not taking diuretics (430.85 +/- 28.58 ng/mL). Serum vitamin B6 and vitamin B12 concentrations were not significantly different between the two groups. CONCLUSIONS: Chronic diuretic use is associated with a significant increase in serum homocysteine concentration, a significant decrease in RBC folate concentration, and no significant change in concentrations of vitamins B6 and B12.

Diuretics↗
PubMed2003

Interactions of human organic anion transporters with diuretics.

The tubular secretion of diuretics in the proximal tubule has been shown to be critical for the action of drugs. To elucidate the molecular mechanisms for the tubular excretion of diuretics, we have elucidated the interactions of human organic anion transporters (hOATs) with diuretics using cells stably expressing hOATs. Diuretics tested were thiazides, including chlorothiazide, cyclothiazide, hydrochlorothiazide, and trichlormethiazide; loop diuretics, including bumetanide, ethacrynic acid, and furosemide; and carbonic anhydrase inhibitors, including acetazolamide and methazolamide. These diuretics inhibited organic anion uptake mediated by hOAT1, hOAT2, hOAT3, and hOAT4 in a competitive manner. hOAT1 exhibited the highest affinity interactions for thiazides, whereas hOAT3 did those for loop diuretics. hOAT1, hOAT3, and hOAT4 but not hOAT2, mediated the uptake of bumetanide. hOAT3 and hOAT4, but not hOAT1 mediated the efflux of bumetanide. hOAT1 and hOAT3, but not hOAT2 and hOAT4 mediated the uptake of furosemide. In conclusion, it was suggested that hOAT1 may play an important role in the basolateral uptake of thiazides, and hOAT3 in the uptake of loop diuretics. In addition, it was also suggested that bumetanide taken up by hOAT3 and/or hOAT1 is excreted into the urine by hOAT4.

Animals↗
PubMed1994

Short term effect of withdrawal of diuretic drugs prescribed for ankle oedema.

OBJECTIVE: To determine the effect of withdrawing diuretic drugs on oedema in patients prescribed them for only ankle oedema, excluding patients with cardiac, hepatic, or renal failure. DESIGN: Randomised controlled trial. SETTING: 15 general practices in the Netherlands. PATIENTS: 1202 patients aged 65 years or older and taking diuretic drugs, 63 of whom were eligible for the trial. MAIN OUTCOME MEASURE: Change in volumetrically determined ankle oedema (oedema index) over six weeks. RESULTS: 34 patients were randomised to stop diuretics and 29 to the control group. In eight patients diuretics had to be restarted. Among patients who had diuretics withdrawn successfully, rebound oedema caused a temporary increase in mean oedema index. The peak level (3.5% (95% confidence interval 1.5% to 5.2%) was reached in the third week, after which the oedema seemed to be returning to the baseline level. CONCLUSION: Few patients who have been prescribed diuretics for only ankle oedema clearly have no contraindications to withdrawing diuretics. If patients are unlikely to have cardiac insufficiency and careful monitoring is provided, withdrawal of diuretics seems to be feasible, though moderate rebound oedema may occur for a short time.

Aged↗
PubMed1980

Comparison of effects of standard diuretics and indanone in isolated toad cornea and bladder.

Short-circuit current (SCC) techniques were used to monitor effects of various diuretic agents on Na+ transport in toad bladder and Cl- transport in toad cornea. In bladder, various agents from different "classes" of diuretics inhibited SCC whereas in cornea only "loop diuretics," i.e., those with a primary site of action in the ascending limb of the loop of Henle, inhibited SCC. Classification of the diuretics based on sensitivity in cornea and bladder revealed that diuretics with a common renal site of action gravitated into common classification groups. Thus, our studies suggested that cornea may be a suitable model of the thick ascending limb of the loop of Henle and that cornea and bladder, studied jointly, may serve as an in vitro system for predicting potential renal sites of action of new diuretics. This system, when used to characterize the new diuretic indanone, revealed that this agent, in all respects, displayed the characteristics of a loop diuretic.

Amiloride↗
PubMed1994

Effect of diuretics on cardiac arrhythmias and left ventricular hypertrophy in hypertension.

Ventricular arrhythmias pose a serious risk in patients with high blood pressure. The concept that diuretics predispose to life-threatening arrhythmias, however, was originally based solely on observations made in patients with severe congestive heart failure pretreated with digitalis and not in patients with high blood pressure. In hypertensive patients, some studies have also indicated that diuretic therapy may be associated with an increase in premature ventricular beats, though most have failed to demonstrate a conclusive link between hypokalemia and the precipitation of such cardiac arrhythmias. Prospective studies, however, have demonstrated that diuretic therapy had no effect on the incidence of serious ventricular arrhythmias in hypertensive patients whether they had left ventricular hypertrophy (LVH) or not, and neither at rest nor during or immediately following dynamic exercise. Correction of diuretic-induced hypokalemia similarly had no effect on the incidence of ventricular arrhythmias. In hypertensive patients, LVH is an independent and particularly sinister risk factor for cardiovascular morbidity and mortality, and its regression is now a specific goal of antihypertensive therapy. Diuretics have been shown to be at least as effective in that respect as other antihypertensive agents. The Veterans Administration Cooperative Study Group reported that after 2 years of treatment, only hydrochlorothiazide of 6 antihypertensive regimens resulted in significant reduction of left ventricular mass. In the Treatment of Mild Hypertension Study, all the antihypertensive drugs used resulted in reductions in LVH but the diuretic caused a significantly greater reduction than other non-diuretic agents. In the Systolic Hypertension in the Elderly Study, which primarily used diuretics, there was a significant reduction in LVH at 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed2003

Do hypertension and diuretic treatment in pregnancy increase the risk of schizophrenia in offspring?

OBJECTIVE: Diuretics prescribed after the first trimester for treatment of hypertension in pregnant women may interfere with normal plasma volume expansion and cause volume depletion. The authors hypothesized that prenatal exposure to diuretics and maternal hypertension might disrupt fetal neurodevelopment and increase the risk of schizophrenia in offspring. METHOD: Using data from the Copenhagen Perinatal Cohort of individuals born between 1959 and 1961, the authors studied the relationship of maternal hypertension and diuretic treatment during pregnancy with the risk of schizophrenia (ICD-8 code 295) in the offspring. Prenatal medical information was linked to the Danish National Psychiatric Register. The effects of maternal hypertension and diuretic treatment were adjusted for the maternal history of schizophrenia, social status of the family breadwinner, mother's age, and concomitant drug treatment during pregnancy. RESULTS: In a risk set of 7,866 individuals, 84 cases of schizophrenia were found (1.1% prevalence). Logistic multiple regression analysis identified the following independent risk factors: maternal hypertension (odds ratio=1.69 [95% CI=1.02-2.80]), diuretic treatment in the third trimester (odds ratio=2.55 [95% CI=1.21-5.37]), and maternal schizophrenia (odds ratio=11.12 [95% CI=4.60-29.91]). Prenatal exposure to both hypertension and diuretic treatment in the third trimester conferred a 4.01-fold (95% CI=1.41-11.40) elevated risk. CONCLUSIONS: Children of mothers with hypertension in pregnancy plus diuretic treatment in the third trimester were at significantly increased risk of developing schizophrenia. In pregnancies complicated by hypertension, diuretics may interfere with aspects of fetal neurodevelopment and thus increase the vulnerability of offspring to the development of schizophrenia later in life.

Child of Impaired Parents↗
PubMed1995

The role of continuous infusion loop diuretics.

OBJECTIVE: To evaluate the role of continuous infusion loop diuretics in selected patient populations, discuss the advantages and disadvantages associated with continuous infusion, and recommend monitoring parameters for the use of continuous infusion therapy. Current dosing guidelines for continuous infusion loop diuretics have not been established, but a summary of previously studied doses is provided. DATA SOURCES: A literature search using MEDLINE, International Pharmaceutical Abstracts, as well as additional references found in pertinent articles. STUDY SELECTION AND DATA EXTRACTION: Clinical studies concerning the use of loop diuretics administered by continuous infusion were evaluated in selected patient populations. All articles and clinical studies were considered for possible inclusion in the review. Information judged to be pertinent by the authors was selected for discussion. DATA SYNTHESIS: Comparative studies in the congestive heart failure (CHF), renal-insufficient, and postcardiac surgery patient populations have shown that loop diuretics administered by continuous infusion are more beneficial than those given by intermittent bolus administration. In adult patients with CHF, furosemide 3-4 mg/h is recommended. In adult and pediatric postcardiac surgery patients, furosemide dosages of 0.05 and 0.1 mg/kg/h have produced diuresis. In patients with renal insufficiency, bumetanide 0.912 mg/h has produced diuresis. Intravenous bolus doses were used in all studies reviewed except 1. These studies have indicated that continuous infusion of the loop diuretics yields diuresis without increasing toxicity. CONCLUSIONS: The use of continuous infusion loop diuretics is a therapeutic alternative for patients requiring diuresis. This form of administration has provided more consistent urine flow, fewer alterations in fluid balances, fewer urinary losses of electrolytes as well as decreased dosage of the diuretic requirements. The disadvantages have not been fully elucidated because of the limited evaluation of this administration method. Few studies have used this method of administration; however, the few data available indicate that continuous infusion of loop diuretics is an efficacious alternative to conventional therapy.

Diuretics↗
PubMed1995

Diuretics, beta-blockers, and the risk for sudden cardiac death in hypertensive patients.

OBJECTIVE: To determine whether the use of non-potassium-sparing diuretics and beta-blockers is associated with an excess risk for sudden cardiac death in hypertensive patients. DESIGN: Case-control study. SETTING: Rotterdam, the Netherlands. PATIENTS: 257 case-patients who had died suddenly while receiving drug therapy for hypertension and 257 living controls also receiving drug therapy for hypertension. MEASUREMENTS: Detailed information on medication use and clinical characteristics of all case-patients and controls was collected from the files of general practitioners. Additional information on medication use was obtained from computerized pharmacy records. RESULTS: Patients receiving non-potassium-sparing diuretics had an increased risk for sudden cardiac death (relative risk, 1.8 [95% CI, 1.0 to 3.1]) compared with a reference group treated primarily with potassium-sparing diuretics. The corresponding relative risk for beta-blocker use was 1.7 (CI, 1.1 to 2.6). The use of non-potassium-sparing diuretics without beta-blockers was associated with a higher risk for sudden death (relative risk, 2.2 [CI, 1.1 to 4.6]) than was concomitant use of non-potassium-sparing diuretics and beta-blockers (relative risk, 1.4 [CI, 0.6 to 3.0]). The risk for sudden cardiac death among recipients of non-potassium-sparing diuretics was more pronounced in those who had been receiving the diuretic for less than 1 year and in those aged 75 years or younger. CONCLUSIONS: The use of non-potassium-sparing diuretics and beta-blockers is associated with an increased risk for sudden cardiac death. This association may offset part of the mortality benefit of these drugs in the treatment of hypertension.

Adrenergic beta-Antagonists↗
PubMed1999

Metabolic and adverse effects of diuretics.

Diuretics are among the most frequently prescribed drugs. They enjoy a very high clinical reputation for safety and efficacy. However, more than 3 decades of clinical investigation have disclosed a number of abnormalities in fluid electrolyte handling, metabolism, and other adverse effects that can complicate therapy with diuretic drugs. Some of these complications are a direct extension of the wanted action of the drug. These include extracellular fluid volume depletion, associated orthostatic hypotension, and prerenal azotemia. Others are not a direct action of the diuretic, but can be explained as an intranephronal compensation to the diuretic action. These include hypokalemia, in part to increased potassium secretion secondary to the enhanced tubular fluid flow and aldosterone secretion induced by diuretic administration. Metabolic abnormalities are usually mild. Hyperglycemia and carbohydrate intolerance have been related to diuretic-induced hypokalemia, which inhibits insulin secretion by the beta cells, and reductions in extracellular fluid volume and cardiac output. This is compounded by increases in catecholamines from sympathetic nerve activity which decrease peripheral glucose utilization. A mild increase in serum cholesterol concentration is seen frequently during initiation of diuretic therapy, but during steady state therapy after 6 to 12 months, values usually return to baseline. Knowledge of the more common adverse effects induced by diuretics helps the physician in predicting patients at risk and taking effective steps to anticipate or treat adverse responses.

Animals↗
PubMed1992

Influence of diuretics, calcium antagonists, and alpha-blockers on insulin sensitivity and glucose tolerance in hypertensive patients.

Treatment with thiazide diuretics causes impaired glucose tolerance, biochemical diabetes, and insulin resistance. The effect of diuretics on glucose tolerance is clearly dose-related. Spironolactone does not impair glucose tolerance, even at high dosage, but differences among other diuretics could be due to comparisons at doses that are not equal. Diuretic-induced changes in glucose metabolism are not conclusively related to altered potassium homeostasis, and impaired glucose tolerance occurs even when relatively low doses of thiazide are combined with potassium-sparing agents. The effects of diuretics on glucose homeostasis are in large part and probably entirely reversible. These disturbances of glucose metabolism have been detected only by detailed biochemical testing, and their clinical relevance is uncertain. In established diabetes, diuretics have a rapid and substantial adverse effect on metabolic control. In nondiabetic subjects, diuretics rarely cause or trigger a serious hyperosmolar nonketotic diabetic syndrome. Otherwise, it is not known whether the metabolic changes cause clinical diabetes or lead to microvascular complications in the long term. Evidence from large outcome trials suggests that biochemical diabetes, glucose intolerance, and insulin resistance do not increase the risk of coronary heart disease in treated hypertensive patients. Diuretics should be avoided in patients with diabetes unless their use is essential. Otherwise, a low dose of thiazide remains as excellent choice for first-line antihypertensive therapy. Dihydropyridine calcium antagonists, diltiazem, and verapamil appear to have no important effects on glucose homeostasis. There is very limited evidence that selective alpha-antagonists increase insulin sensitivity. The importance of metabolic differences between drug classes will be established only by comparative outcome trials with coronary events as the end point.

Adrenergic beta-Antagonists↗
PubMed1992

Prescription of diuretic drugs and monitoring of long-term use in one general practice.

A cross-sectional survey of the prescription and monitoring of diuretic drugs for long-term use was performed in a Nottinghamshire training practice, which has 7619 patients. It was found that 330 patients were long-term users of diuretic drugs, with 79% of these patients aged 60 years or over. Twenty three different diuretic drugs were prescribed with a total cost of 13,643 pounds per year. A few drugs accounted for a disproportionate amount of the total cost, with combination diuretic drugs being particularly expensive. The most common indications for the prescription of diuretic drugs were hypertension and congestive cardiac failure. General practitioners initiated the prescribing of diuretic drugs in 87% of cases, with only a small proportion being prescribed by hospital doctors. One third of the patients had no record of urea and electrolyte levels in their notes after commencing treatment with a diuretic drug. On the basis of these findings recommendations are made for the initiation and monitoring of the long-term use of diuretic drugs.

Adult↗
PubMed1990

Use of renal artery infusion in dogs for evaluation of diuretics.

In this paper we report on a series of experiments evaluating a model of renal artery infusion (RAI) as a screening technique for comparison of new diuretics, and test some assumptions underlying its use. The femoral artery and vein of Beagle dogs were catheterized for the infusion of solutions, measurement of arterial blood pressure and the sampling of arterial blood. The left kidney was isolated through a flank incision, and a 27 ga. needle, connected to PE10 tubing, was inserted into the renal artery for administration of test diuretics. Both ureters were catheterized for collection of urine. Effects on renal function were assessed during control, drug infusion, and recovery periods. At low doses, the loop diuretics, furosemide (FUR) and MK447, increased urinary excretion within the first 15 min of infusion. The effect of muzolimine, another loop diuretic, was delayed until about 45 min after initiation of infusion. Renal function returned to baseline after cessation of drug infusion. At high doses, excretion was increased by all the loop diuretics within the first 15 min of infusion. The response to muzolimine and MK447 was prolonged well into the recovery period, while that to furosemide returned promptly to baseline. Two distal diuretics, hydrochlorothiazide and amiloride, caused a significant increase in urinary excretion at both low and high doses. The magnitude of the response was significantly less than for the loop diuretics. Low doses of the loop diuretics had very little effect on the contralateral kidney; however, at high doses the excretion rate of the contralateral kidney was significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The diuretic dilemma and the management of mild hypertension.

Diuretics are presently used as antihypertensive medications as first-step monotherapy or in combination with adrenergic-inhibiting agents in the majority of hypertensive patients in the United States. A 30-year experience has demonstrated that blood pressure is lowered to as great or greater degree with diuretics than with many of the antihypertensive drugs presently available, including converting enzyme inhibitors, calcium entry blockers, beta- or alpha-adrenergic inhibitors, or centrally acting sympatholytic agents. Diuretics appear to be especially effective in the elderly and in black patients. All of the major hypertension clinical trials on which we base our decisions for treatment have employed diuretics as first-step therapy, with a reduction in morbidity and mortality. The debate concerning the long-term safety of diuretic therapy has focused on the United States Multiple Risk Factor Intervention Trial results and several papers suggesting that the lipid-raising or potassium-lowering properties of diuretics may produce adverse effects. Suggestions have been made that the use of other drugs without metabolic side effects may result in greater benefit with less risk, especially in the management of mild hypertension where the risk of the disease is not immediate or great. A review of the MRFIT and lipid data from long-term studies have failed to establish the "toxicity" of diuretic agents. In addition, recent studies have not confirmed previous observations that diuretic-induced hypokalemia increases ventricular ectopy or contributes to sudden death.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1987

The value of serum magnesium determination in hypertensive patients receiving diuretics.

Some clinicians contend that hypomagnesemia is a common problem in patients receiving diuretic therapy and that routine serum magnesium determinations may be indicated in such patients. We determined serum magnesium (Mg++) levels in 354 patients with uncomplicated hypertension. No significant difference was observed in the mean Mg++ between the 245 diuretic-treated patients and the 109 patients not receiving diuretics, 0.965 vs 0.97 mmol/L (1.93 vs 1.94 mEq/L). When analyzed by type of diuretic, there were statistically significant differences in the mean serum Mg++ concentrations between those receiving thiazides, 0.94 mmol/L (1.87 mEq/L); those receiving no diuretics, 0.97 mmol/L (1.94 mEq/L); and those receiving triamterene-containing diuretics, 1.01 mmol/L (2.01 mEq/L). These absolute differences, however, were clinically quite small, and hypomagnesemia was uncommon. Neither patient age, the duration of diuretic use, nor the serum potassium level correlated with Mg++. With respect to dose, those receiving 100 mg/d of hydrochlorothiazide had the lowest Mg++ concentrations and the greatest prevalence of hypomagnesemia (12%), defined as Mg++ less than 0.75 mmol/L (1.5 mEq/L). Serum Mg++ need not routinely be determined in patients with uncomplicated hypertension who are receiving triamterene-containing diuretics or low-dose (50 mg/d or less) hydrochlorothiazide.

Adolescent↗
PubMed1986

'Diuretic-resistant' ascites. Observations on pathogenesis.

Hepatic sinusoidal hydrostatic-oncotic balance was measured in 25 patients with alcoholic liver disease and varying severity of sodium retention. Eight patients had diuretic-responsive ascites and 17 patients had diuretic-resistant ascites. Net "transfer pressure," the force theoretically favoring fluid transudation across the hepatic sinusoids, was similar in the diuretic-responsive and diuretic-resistant groups and was unrelated to the fractional excretion of sodium after intravenous administration of furosemide. Fractional sodium excretion was significantly less in resistant than in responsive patients, but kaliuresis after furosemide was similar. Baseline creatinine clearance was similar in the two groups, but maximal oral diuretic therapy caused a significantly steeper rise in serum creatinine concentration in resistant than in responsive patients, despite less weight loss. More marked hepatic sinusoidal hydrostatic-oncotic imbalance was not present in patients with diuretic-resistant ascites. Similar kaliuretic response despite reduced natriuretic response to furosemide suggested that the proximal tubule is the site of enhanced sodium resorption in these patients. Renal insufficiency developing during long-term diuretic treatment is an important factor limiting natriuresis in patients with diuretic-resistant ascites.

Ascites↗