A dose‐response study of orally administered torsemide in patients with ascites due to cirrhosis

Jj, Applefeld; Rj, Kasmer; Lj, Hak; Ge, Dukes; Dp, Wermeling; Cj, McClain

doi:10.1111/j.1365-2036.1994.tb00306.x

Cited by 9 publications

(2 citation statements)

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“…Thiazide and loop diuretics, mineralocorticoid receptor antagonists, and vasopressin antagonists ameliorate fluid retention in heart failure, hepatic cirrhosis, and nephrotic syndrome. [134][135][136][137] In contrast, there are no reports of a favorable effect of SGLT2 inhibitors to reduce the edema of heart failure or the ascites of hepatic cirrhosis. Observations about decongestion are difficult to interpret when patients are being concurrently treated with an intensified regimen of loop diuretics.…”

Section: Effect Of Sglt2 Inhibitors On Edema and Congestionmentioning

confidence: 99%

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

2023

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SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an interplay between the degree of upregulation of SGLT2 and sodium-hydrogen exchanger 3, the extent to which downstream compensatory tubular mechanisms are activated, and (potentially) the volume set point in individual patients. A comprehensive review and synthesis of available studies reveals several renal response patterns with substantial variation across studies and clinical settings. However, the common observation is an absence of a large acute or chronic diuresis or natriuresis with these agents, either when given alone or combined with other diuretics. This limited response results from the fact that renal compensation to these drugs is rapid and nearly complete within a few days or weeks, preventing progressive volume losses. Nevertheless, the finding that fractional excretion of glucose and lithium (the latter being a marker of proximal sodium reabsorption) persists during long-term treatment with SGLT2 inhibitors indicates that pharmacological tolerance to the effects of these drugs at the level of the proximal tubule does not meaningfully occur. This persistent proximal tubular effect of SGLT2 inhibitors can be hypothesized to produce a durable improvement in the internal set point for volume homeostasis, which may become clinically important during times of fluid expansion. However, it is difficult to know whether a treatment-related change in the volume set point actually occurs or contributes to the effect of these drugs to reduce the risk of major heart failure events. SGLT2 inhibitors exert cardioprotective effects by a direct effect on cardiomyocytes that is independent of the presence of or binding to SGLT2 or the actions of these drugs on the proximal renal tubule. Nevertheless, changes in the volume set point mediated by SGLT2 inhibitors might potentially act cooperatively with the direct favorable molecular and cellular effects of these drugs on cardiomyocytes to mediate their benefits on the development and clinical course of heart failure.

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Section: Effect Of Sglt2 Inhibitors On Edema and Congestionmentioning

confidence: 99%

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

2023

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“…Torasemide is also available as an intravenous application. (98,100,113) In terms of efficacy, torasemide is a high-ceiling, long-acting diuretic, which shows a linear and rapid rise in the dose-effect curve in a higher dose range. Bioavailability is 80Ϫ90%, with a protein binding of 98%.…”

Section: In No Way Do Normal Potassium Values Rule Out Hyperaldosteronism!mentioning

confidence: 99%

Oedema and ascites

Hepatology Textbook and Atlas

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Water and electrolyte balance 294 2 Definition 295 2.1 States of hydration 295 2.2 Oedema and anasarca 295 2.3 Ascites 296 3 Pathogenesis 296 3.1 Oedematization 296 3.2 Formation of ascites 297 3.2.1 Mechanical factors 297 3.2.2 Biochemical factors 298 3.2.3 Increase in renal sodium retention 300 3.2.4 Theories of ascites formation 300 4 Aetiology of ascites 302 4.1 Differential diagnosis 302 4.2 Hepatogenic ascites 302 5 Diagnosis of ascites 303 5.1 Clinical findings 303 5.2 Imaging procedures 304 5.3 Laboratory diagnosis 305 6 Complications of ascites 308 7 Spontaneous bacterial peritonitis 308 7.1 Definition 3 0 8 7.2 Forms and frequency 308 7.3 Pathogenesis and predisposing factors 309 7.4 Clinical aspects 309 7.5 Prophylaxis and therapy 309 8 Conservative therapy of ascites 310 8.1 Prophylaxis 310 8.2 Basic therapy (stage I) 311 8.3 Diuretic therapy (stage II) 312 8.3.1 Pharmacology of diuretics 312 8.3.2 Side effects 314 8.3.3 Hyponatraemia 314 8.3.4 Resistance to diuretics 314 8.4 Osmotic diuresis (stage III) 314 8.5 Paracentesis (stage IV) 315 9 Refractory ascites 316 10 Invasive therapeutic procedures 316 10.1 Ascites reinfusion 316 10.2 Peritoneovenous shunt 317 10.3 TIPS 320 11 Surgical treatment 321 12 Liver transplantation 322 ț References (1Ϫ240) 323 (Figures 16.1Ϫ16.17; tables 16.1Ϫ16.19) 16 Oedema and ascites 1 Water and electrolyte balance ᭤ Water is an indispensable factor of life. By means of carefully coordinated regulatory mechanisms, the water equilibrium and hence the reservoir of body water is held constant. It is important to keep water intake and output in balance to maintain isovolaemia. (s. fig. 16.1) Water is present in a free (non-osmotically bound) state and as a chemically bound hydrate solid structure. • The clearance of freewater is controlled by vasopressin; it is calculated from the volume of urine/minute minus the osmolal clearance. A normal daily fluid intake of 1,700Ϫ2,200 ml (25Ϫ30 ml/kg BW) in addition to some 300 ml oxidation water is balanced by a fluid discharge of approximately 1,500 ml as urine, about 100 ml in stools, roughly 600 ml as perspiration and some 400 ml as expired air. (s. fig. 16.1) About 60% of the body's weight (ca. 55% in women) consists of water. The reservoir of body water is distributed between the intracellular space (ca. 40% of BW) and the extracellular space (ca. 20% of BW). The extracellular compartment consists of plasma fluids (ca. 4% of BW) and interstitial water (ca. 16% of BW), the latter also containing transcellular water (ca. 2.5% of BW). Because of its high degree of permeability, the body water is evenly shared between the intracellular and extracellular compartments. The water distribution between plasma and interstitium, regulated by Starling's forces, depends on the hydrostatic and colloidosmotic pressure gradients along the capillary walls. • Disturbances in the excretion of water are derived from (1.) an increase in ADH activity, (2 ( ( .) a reduction in distal filtrates available in the nephron, and (3.) greater absorption of wat...

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Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis

Benmassaoud

Freeman

Roccarina

et al. 2020

Cochrane Database of Systematic Reviews

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BackgroundApproximately 20% of people with cirrhosis develop ascites. Several di erent treatments are available; including, among others, paracentesis plus fluid replacement, transjugular intrahepatic portosystemic shunts, aldosterone antagonists, and loop diuretics. However, there is uncertainty surrounding their relative e icacy. ObjectivesTo compare the benefits and harms of di erent treatments for ascites in people with decompensated liver cirrhosis through a network meta-analysis and to generate rankings of the di erent treatments for ascites according to their safety and e icacy. Search methodsWe searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until May 2019 to identify randomised clinical trials in people with cirrhosis and ascites. Selection criteriaWe included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis and ascites. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. Data collection and analysisWe performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis (Review)

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A dose‐response study of orally administered torsemide in patients with ascites due to cirrhosis

Cited by 9 publications

References 7 publications

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes

Oedema and ascites

Treatment for ascites in adults with decompensated liver cirrhosis: a network meta-analysis

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