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JACC. Heart Failure Dec 2021The increasing burden of heart failure (HF) and emerging knowledge regarding chloride as a prognostic marker in HF have increased the interest in the pathophysiology and... (Review)
Review
The increasing burden of heart failure (HF) and emerging knowledge regarding chloride as a prognostic marker in HF have increased the interest in the pathophysiology and interactions of chloride abnormalities with HF-related factors and treatments. Chloride is among the major electrolytes that play a unique role in fluid homeostasis and is associated with cardiorenal and neurohormonal systems. This review elucidates the role of chloride in the pathophysiology of HF, evaluates the effects of treatment on chloride (eg, diuretic agents cause higher urinary chloride excretion and consequently serum hypochloremia), and discusses recent evidence for the association between chloride levels and mortality.
Topics: Chlorides; Diuretics; Electrolytes; Heart Failure; Humans; Water-Electrolyte Imbalance
PubMed: 34857174
DOI: 10.1016/j.jchf.2021.07.006 -
Current Diabetes Reports Feb 2018In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events,... (Review)
Review
PURPOSE OF REVIEW
In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes.
RECENT FINDINGS
These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents. Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in type 2 diabetes and of new-onset diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with type 2 diabetes and hypertension.
Topics: Antihypertensive Agents; Diabetes Mellitus, Type 2; Diuretics; Humans; Sodium Chloride Symporter Inhibitors; Thiazides
PubMed: 29399724
DOI: 10.1007/s11892-018-0976-6 -
Current Drug Targets 2020Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups,... (Review)
Review
BACKGROUND
Urea Transporters are a family of membrane channel proteins that facilitate the passive transport of urea across the plasma membrane. UTs are divided into two subgroups, UT-A and UT-B. UT-As are primarily located in renal tubule epithelia and UT-Bs are highly expressed in renal descending vasa recta and extrarenal multiple tissues. Various urea transporter knockout mice exhibit low urine concentrating ability, which suggests that UTs are novel diuretic targets. With highthroughput screening of small molecule drug-like compound libraries, various potent UT inhibitors with IC50 at nanomolar level were identified. Furthermore, selective UT inhibitors exhibit diuretic activity without disturbing electrolyte and metabolism balance, which confirms the potential of UTs as diuretic targets and UT inhibitors as novel diuretics that do not cause electrolyte imbalance.
OBJECTIVE
This review article summarizes the identification and validation of urea transporter as a potential diuretic target and the discovery of small molecule UT inhibitors as a novel type of diuretics.
CONCLUSION
UTs are a potential diuretic target. UT inhibitors play significant diuresis and can be developed to diuretics without disturbing electrolyte balance.
Topics: Animals; Cell Line; Diuresis; Diuretics; Humans; Membrane Transport Proteins; Mice; Mice, Knockout; Small Molecule Libraries; Structure-Activity Relationship; Urea; Water-Electrolyte Balance; Urea Transporters
PubMed: 31782365
DOI: 10.2174/1389450120666191129101915 -
Seminars in Dialysis Sep 2016While oral diuretics are commonly used in patients with chronic kidney disease for the management of volume and blood pressure, they are often discontinued upon...
While oral diuretics are commonly used in patients with chronic kidney disease for the management of volume and blood pressure, they are often discontinued upon initiation of dialysis. We suggest that diuretics are considerably underutilized in peritoneal dialysis and haemodialysis patients despite numerous potential benefits and few side effects. Moreover, when diuretics are used, optimal doses are not always prescribed. In peritoneal dialysis, the use of diuretics can improve volume status and minimize the need for higher glucose-containing solutions. In patients on haemodialysis, diuretics can help lessen interdialytic weight gain, resulting in decreased ultrafiltration rates and fewer episodes of intradialytic hypotension. This paper will review the mechanism of action of diuretics in patients with renal insufficiency, quantify the risk of side effects and elaborate on the potential advantages of diuretic use in peritoneal dialysis and hemodialysis patients with residual kidney function.
Topics: Diuretics; Humans; Hypotension; Kidney Failure, Chronic; Peritoneal Dialysis; Renal Dialysis
PubMed: 27060970
DOI: 10.1111/sdi.12483 -
Cardiology Journal 2022Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different...
Current hypertension guidelines suggest various strategies to reduce blood pressure levels, thereby reducing cardiovascular events: combinations of drugs with different mechanisms of action, such as an angiotensin converting enzyme inhibitors (ACEIs) and a diuretic, are the cornerstone of the modern treatment of hypertension, also as initial therapy. Among ACEIs, zofenopril has been shown to be effective in the management of hypertension both as monotherapy and in combination with a diuretic: zofenopril/hydrochlorothiazide fixed dose combination is particularly useful to improve treatment adherence through simplification of treatment regimen. Moreover, thanks to the sulfhydryl group, zofenopril has some peculiar properties (higher lipophilicity and tissue penetration, lower bradykinin-dependent effect, higher affinity for, and more persistent binding to, tissue ACE, significant antioxidant effect), which may account for the cardioprotective effects of the drug demonstrated in both pre-clinical studies and randomized clinical trials. The positive impact of zofenopril on clinical outcomes has been extensively documented by the SMILE program, including several clinical trials in patients with different conditions of myocardial ischemia treated with zofenopril: the results of the SMILE program, demonstrating the benefits of zofenopril vs. placebo and other ACEIs, emphasize the importance of a differentiated approach to patients with ischemic heart disease, based on a careful choice of the adopted agent, in order to improve the overall impact of pharmacological treatment on clinical outcomes.
Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Captopril; Diuretics; Humans; Hypertension; Myocardial Ischemia
PubMed: 34622438
DOI: 10.5603/CJ.a2021.0113 -
Cardiorenal Medicine 2023Acute decompensated heart failure (ADHF) has the highest rate of hospital readmission among all medical conditions and portends a significant financial burden on... (Review)
Review
Acute decompensated heart failure (ADHF) has the highest rate of hospital readmission among all medical conditions and portends a significant financial burden on healthcare systems worldwide. Hospitalization for ADHF is primarily driven by congestion, with intravenous loop diuretics representing the cornerstone of therapy. However, it is well described that a significant subset of patients is discharged with residual fluid overload. While the cause of the incomplete decongestion is multifactorial, the development of diuretic resistance is a well-characterized contributing factor with consequent poor outcomes. Moreover, the therapeutic response to diuretics is known to lack predictability. Extracorporeal ultrafiltration (a mechanical pump-driven therapy) has emerged as an option to overcome shortcomings of the diuretics. It allows clinicians to customize the volume and the rate of fluid removal to the needs and clinical characteristics of the patients. The results of the currently available studies indicate that this therapy is associated with more efficient fluid and sodium removal compared to medical therapy, hence leading to reduction in the rate of readmissions and a potential salutary impact on the financial burden associated with the care of these patients. While isolated ultrafiltration can be performed by conventional machines used for renal replacement therapy, the advent of simplified, portable, and user-friendly devices that are specifically designed for extracorporeal ultrafiltration therapy has further enhanced the interest in this therapeutic modality and increased the potential for its more widespread use. Further, development in this direction through device miniaturization may extend the horizons of indications and the applicability of this therapy even in the ambulatory settings.
Topics: Humans; Ultrafiltration; Heart Failure; Diuretics; Renal Replacement Therapy; Hospitalization
PubMed: 36323267
DOI: 10.1159/000527204 -
Medicina Clinica Jan 2024
Topics: Humans; Diuretics; Heart Failure; Drug Resistance; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 37919121
DOI: 10.1016/j.medcli.2023.10.001 -
Pediatric Nephrology (Berlin, Germany) Sep 2021The use of diuretics is extremely frequent in sick neonates, the more so in very premature newborn infants. The use of diuretics in patients whose kidney function is... (Review)
Review
The use of diuretics is extremely frequent in sick neonates, the more so in very premature newborn infants. The use of diuretics in patients whose kidney function is immature necessitates a thorough knowledge of renal developmental physiology and pathophysiology. This review presents the basic aspects of body fluid homeostasis in the neonate, discusses the development of kidney function, and describes the mechanisms involved in electrolyte and water reabsorption along the nephron. Diuretics are then classified according to the site of their action on sodium reabsorption. The use of diuretics in sodium-retaining states, in oliguric states, in electrolyte disorders, and in arterial hypertension, as well as in a few specific disorders, is presented. Common and specific adverse effects are discussed. Recommended dosages for the main diuretics used in the neonatal period are given. New developments in diuretic therapy are briefly mentioned.
Topics: Diuretics; Humans; Infant, Newborn; Infant, Premature
PubMed: 33481099
DOI: 10.1007/s00467-021-04921-3 -
Nederlands Tijdschrift Voor Geneeskunde May 2023Loop diuretics are the cornerstone of the treatment of volume overload in decompensated heart failure. However, often complete decongestion cannot be achieved rapidly... (Randomized Controlled Trial)
Randomized Controlled Trial
Loop diuretics are the cornerstone of the treatment of volume overload in decompensated heart failure. However, often complete decongestion cannot be achieved rapidly with loop diuretics alone, partly due to compensatory upregulation of sodium resorption at other parts of the nephron. These compensatory mechanisms can be antagonized by using a combination of diuretics. In earlier research, a number of those combinations have been investigated, but no diuretic combination has been proven to be both efficient and safe yet. A recent multicenter, double-blind, randomized, placebo-controlled study - performed by Mullens et al. in 2022 - investigated adding acetazolamide (Diamox) to loop diuretics in patients with decompensated heart failure. They found that a higher rate of decongestion was achieved with the addition of acetazolamide without seemingly more side effects. The addition of acetazolamide can be considered in the treatment of decompensated heart failure.
Topics: Humans; Diuretics; Acetazolamide; Sodium Potassium Chloride Symporter Inhibitors; Heart Failure; Combined Modality Therapy
PubMed: 37257097
DOI: No ID Found -
NeoReviews Mar 2022Understanding physiologic water balance and homeostasis mechanisms in the neonate is critical for clinicians in the NICU as pathologic fluid accumulation increases the... (Review)
Review
Understanding physiologic water balance and homeostasis mechanisms in the neonate is critical for clinicians in the NICU as pathologic fluid accumulation increases the risk for morbidity and mortality. In addition, once this process occurs, treatment is limited. In this review, we will cover fluid homeostasis in the neonate, explain the implications of prematurity on this process, discuss the complexity of fluid accumulation and the development of fluid overload, identify mitigation strategies, and review treatment options.
Topics: Diuretics; Homeostasis; Humans; Infant, Newborn; Water-Electrolyte Balance; Water-Electrolyte Imbalance
PubMed: 35229135
DOI: 10.1542/neo.23-3-e189