Diuretic Effect Research Articles

Combination diuretic therapies in heart failure: Insights from GUIDE-IT

IntroductionDiuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT. MethodsPatients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups. ResultsThere was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p < 0.0001). On subgroup analysis, both the BNP-guided group as well as the control group had reduced time to first hospitalization in the CDT group compared to those who did not require CDT (BNP group: 287.503 days vs 402.475 days, p ≤0.0001; control group 248.698 days vs 399.035 days, p = 0.0009). ConclusionUse of CDT is associated with earlier time to hospitalization, though no association was identified with increased all-cause mortality. Further prospective studies are likely needed to determine the true risk and benefits of combination diuretic therapy.

Glucocorticoid-induced acute diuresis in rats in relation to the reduced renal expression of sodium-dependent cotransporter genes

Although several studies have shown that glucocorticoids exert diuretic effects in animals and humans, the underlying mechanism responsible for the acute diuretic effect remains obscure. Here we examined the mechanism in terms of gene-expression. We observed that glucocorticoids, including dexamethasone (Dex) and prednisolone (PSL), acutely induced diuresis in rats in a dose-dependent manner. Free water clearance values were negative after Dex or PSL treatment, similar to those observed after treatment with osmotic diuretics (furosemide and acetazolamide). Dex significantly increased the urinary excretion of sodium, potassium, chloride, glucose, and inorganic phosphorus. Renal microarray analysis revealed that Dex significantly altered the renal expression of genes related to transmembrane transport activity. The mRNA levels of sodium/phosphate (NaPi-2a/Slc34a1, NaPi-2b/Slc34a2, and NaPi-2c/Slc34a3) and sodium/glucose cotransporters (Sglt2/Slc5a2) were significantly reduced in the Dex-treated kidney, being negatively correlated with the urinary excretion of their corresponding solutes. Dex did not affect renal expression of the natriuretic peptide receptor 1 (Npr1) gene, or the expression, localization, and phosphorylation of aquaporin-2 (AQP2), a water channel protein. These findings suggest that the acute diuretic effects of glucocorticoids might be mediated by reduced expression of sodium-dependent cotransporter genes.

Pharmacological mechanisms involved in the diuretic activity of the ethanol-soluble fraction of Baccharis milleflora (Less.) DC. - An ethnopharmacological investigation

Ethnopharmacological relevanceBaccharis milleflora (Less.) DC. is a plant native to Brazil that is frequently used in traditional medicine as a diuretic and antihypertensive. However, even though it is traditionally used for these purposes, its diuretic and hypotensive effects have not been fully elucidated. AimInvestigate the cardiorenal effects of the ethanol-soluble fraction (ESBM) of Baccharis milleflora in normotensive rats. Materials and methodsCladodes of B. milleflora were analyzed using light and scanning electron microscopy to provide anatomical data to support quality control. Subsequently, the ESBM was obtained and analyzed using LC-DAD-MS, and its components were annotated. The acute toxicity of ESBM was assessed in female Wistar rats. The acute and prolonged diuretic and hypotensive effects were then studied in Wistar rats. Finally, we assessed the mechanisms responsible for the diuretic effects of ESBM, including the activity of renal Na+/K+/ATPase, angiotensin-converting enzyme, and erythrocyte carbonic anhydrase. Additionally, we also investigated the involvement of bradykinin, prostaglandins, and nitric oxide. ResultsFrom LC-DAD-MS data, thirty-three metabolites were identified from ESBM, including chlorogenic acids, glycosylated phenolic derivatives, C-glycosylated flavones, and O-glycosylated flavonols. No signs of acute toxicity were observed in female rats. The findings showed that ESBM had significant diuretic and natriuretic effects, as well as a potassium-sparing effect. The treatment with ESBM was able to significantly decrease serum levels of creatinine and malondialdehyde, and also significantly increase levels of nitrite, an indirect marker of nitric oxide bioavailability. Furthermore, pre-treatment with L-NAME abolished all diuretic effects induced by ESBM. ConclusionThis study presented important morpho-anatomical and phytochemical data that support the quality control of Baccharis milleflora. The ESBM exhibited a significant diuretic and natriuretic effect following acute and seven-days repeated treatment in Wistar rats, without affecting renal potassium elimination. These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. This study suggests the potential use of B. milleflora preparations in clinical situations where a diuretic effect is needed.

Formulation and Evaluation of Diuretic Activity of Polyherbal Drug in Rats

An attempt was made in this study to investigate the diuretic activity of an ethanolic extract of a polyherbal formulation containing four drugs: seeds of Coriandrum sativum, buds of Syzigiumaromaticum, leaves of Ocimum sanctum, and curcumin (Curcuma longa), as well as leaves of Syzigiumaromaticum. According to the findings of this investigation, the extract of a polyherbal formulation (including seeds of Coriandrum sativum, buds and leaves of Syzigiumaromaticum&amp; leaves of Ocimum sanctum, and Curcuma longa) possessed substantial activity. Various quantities of Polyherbal formulations (200 and 400 mg/kg), furosemide (10 mg/kg), and vehicle were given orally to rats (n = 6 animals per group), and the urine output was collected after 24 hours. All concentrations of Polyherbal formulation exhibited a dose-dependent relationship when compared to the control animals in the study. According to the findings of this study, the Polyherbal formulations have significant diuretic effect in rats when tested in the above-mentioned experimental model. That polyherbal formulation extract has such potent effect may be due to their ability to stimulate the excretion of Na+, K+, and Cl- concentrations in urine while also increasing the amount of urine excreted by the body. As diuretics, medicinal herbs are a key source of supply. When it comes to diuretics, both mono- and poly-herbal formulations have been employed successfully

Prescribing Pattern and Effect of Diuretics in the Management of Ascites: A Comprehensive Study in a Tertiary Care Hospital

Prescribing Pattern and Effect of Diuretics in the Management of Ascites: A Comprehensive Study in a Tertiary Care Hospital

Molecular Docking of Nigella Sativa L. with PXR Receptors and the Effect of Thymoquinone on PXR Expression in HepG2 Cells

ABSTRACT. The interaction between herbal remedies and drugs is a fascinating phenomenon that might cause therapeutic complications in patients. Warfarin is an anticoagulant drug that provides anti-blood-clotting effects by inhibiting the formation of vitamin K-dependent coagulation factors, and warfarin interacts with the nuclear receptor PXR, subsequently modulating cytochrome P450 during the metabolism process. St. John's wort, an herbal medicine with antidepressant effects, can alter the pharmacokinetics of warfarin. Thymoquinone is one of the active compounds in N. sativa and has pharmacological activities such as anticoagulant, antidiabetic, diuretic, antidepressant, and anti-inflammatory effects. In this study, we investigated the compounds in Nigella sativa (N. sativa) against pregnane X receptor (PXR) and evaluated the impact of thymoquinone (TQ) administration on PXR expression in HepG2 cells. The molecular docking analysis was conducted utilizing the Molecular Operating Environment (MOE) with the PXR (PDB ID: 7AXJ). At the same time, the PXR gene expression was measured using RT-PCR instruments. The RMSD value in docking represents the deviation criteria between the native ligand position and the redocking position result, indicating the capability of MOE and PDB qualification for performing molecular docking. The docking analysis showed that warfarin had the strongest binding energy (7AXJ -6.0507) by forming hydrogen binding type on Arg410. Despite TQ being the major component, it also displayed a high affinity for the two PDB IDs (7AXJ -4.5962). Furthermore, the concurrent administration of warfarin and TQ (19.27 μM) in HepG2 cells showed a significant reduction in the relative mRNA expression of the PXR gene. Given the above-mentioned findings, our study adequately enables us to predict the mechanism behind herb-drug interactions (HDIs) implicating N. sativa, specifically the TQ compound to warfarin metabolism via the activation of the PXR receptor. Keywords: Thymoquinone, expression mRNA, PXR, molecular docking, HepG2 cells.

Sex and circadian regulation of metabolic demands in the rat kidney: A modeling analysis.

Renal hemodynamics, renal transporter expression levels, and urine excretion exhibit circadian variations. Disruption of these diurnal patterns is associated with the pathophysiology of hypertension and chronic kidney disease. Renal hemodynamics determines oxygen delivery, whereas renal transport and metabolism determines oxygen consumption; the balance between them yields renal oxygenation which also demonstrates 24-h periodicity. Another notable modulator of kidney function is sex, which has impacts on renal hemodynamics and transport function that are regulated by as well as independent of the circadian clock. The goal of this study was to investigate the diurnal and sexual variations in renal oxygen consumption and oxygenation. For this purpose, we developed computational models of rat kidney function that represent sexual dimorphism and circadian variation in renal hemodynamics and transporter activities. Model simulations predicted substantial differences in tubular Na+ transport and oxygen consumption among different nephron segments. We also simulated the effect of loop diuretics, which are used in the treatment of renal hypoxia, on medullary oxygen tension. Our model predicted a significantly higher effect of loop diuretics on medullary oxygenation in female rats compared to male rats and when administered during the active phase.

Effects of Zibotentan Alone and in Combination with Dapagliflozin on Fluid Retention in Patients with CKD.

Endothelin receptor antagonists (ERAs) reduce albuminuria but are limited by fluid retention risk, particularly in patients with chronic kidney disease (CKD). Combining ERAs with sodium-glucose cotransporter 2 (SGLT2) inhibitors, which have diuretic effects, offers a promising strategy to mitigate fluid retention. In this post-hoc analysis of the ZENITH-CKD trial, we assessed fluid dynamics in patients with CKD treated with the ERA zibotentan alone, and in combination with the SGLT2 inhibitor dapagliflozin. In ZENITH-CKD, 508 patients with CKD (estimated glomerular filtration rate ≥ 20 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio of 150-5000 mg/g) were randomized to treatment with placebo, dapagliflozin 10 mg plus placebo, zibotentan (0.25, 1.5 or 5 mg) plus dapagliflozin 10 mg and zibotentan 5 mg plus placebo. We evaluated correlations between changes in fluid retention markers and bioimpedance-measured extracellular fluid (ECF) in response to zibotentan treatment. We used Cox proportional hazards regression to assess the association between zibotentan/dapagliflozin treatment, baseline characteristics, and fluid retention, and the relationship between zibotentan plasma exposure and fluid retention. After 3 weeks of treatment with zibotentan 0.25, 1.5 or 5 mg plus dapagliflozin 10 mg, changes in body weight (β=0.36 [95%CI 0.26,0.45]) per kg, B-type natriuretic peptide (β=0.38 [95%CI 0.22, 0.54]) per doubling, and hemoglobin (β=-0.29 [95%CI -0.48, -0.10]) per g/dL were independently associated with changes in ECF. Higher doses of zibotentan were associated with significantly higher risk of fluid retention compared to dapagliflozin alone (zibotentan 5 mg HR 8.50 (95%CI 3.40, 21.30). The hazard ratio attenuated when zibotentan was combined with dapagliflozin (HR zibotentan/dapagliflozin 5/10 mg 3.09 [95%CI 1.08, 8.80], zibotentan/dapagliflozin 1.5/10 mg 2.70 [95%CI 1.44, 5.07] and zibotentan/dapagliflozin 0.25/10 mg HR 1.21 [95%CI 0.50, 2.91]). The risk of fluid retention was higher with higher zibotentan exposure and lower eGFR. High doses of zibotentan were associated with a higher risk of fluid retention, which was attenuated with lower doses and the addition of dapagliflozin.

Use of humic acids in the treatment of genitourinary diseases

Currently, diseases of the urogenital system has acquired medical and social importance. This is primarily due to the significant prevalence of this group of diseases in the structure of general morbidity, disability, and mortality and their frequent recurrence and effect on the somatic and emotional state of the patient. In addition to socio-demographic problems, urogenital disorders have significant economic consequences. The total annual costs of treating uronephrological diseases, including accompanying therapy, are estimated at 40 billion US dollars. However, according to expert forecasts, by 2030, the prevalence of this group of diseases is expected to increase by 25%, as well as direct costs of disease treatment and indirect costs associated with partial or total disability due to disease development and premature death. Thus, searching for and developing new drugs for the treatment of diseases of the urogenital organs are crucial. Chemical compounds, potentially significant in this aspect, can be obtained by organic synthesis and isolated from natural sources. Thus, exploring the potential of natural compounds that have high biological activity and favorable safety profile is a significant reason to realize and address this issue. An interesting but understudied groups of natural compounds of plant origin are humic substances. Recent preclinical studies have shown that they are able to exert antitumor, nephroprotective, and diuretic effects and exhibit antibacterial and antifungal properties. This review aimed to summarize and systematize currently available information on the known pharmacological effects and possible mechanisms of action of humic acids and the prospects for their use in the treatment and prevention of genitourinary diseases.

Study of the influence of the extract of pipsissewa on cell cultures

The development of new diuretics of plant origin is an actual direction. Chimaphila umbellata (L.) is a perennial herb with diuretic, astringent, analgesic and other effects; and it can treat various conditions such as edema, dropsy, etc. Pipsissewa herb helps the removal of nitrogenous and chloride salts from the body due to the content of arbutin glycoside, tannins (up to 5 %). The aim. Evaluation of the effect of pipsissewa extract on L929 cell culture. Materials and methods. Cell line L929 (fibroblasts of mouse adipose tissue) was obtained in the low-temperature bank of the Institute of Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine. Cells were cultured in DMEM medium (Bio West, France) enriched with 10 % FBS (Lonza, Germany) with 1 % antibiotic-antimycotic (Bio West, France), in a CO2 incubator (Thermo Fisher Scientific, USA) at 37 ºС in an atmosphere with 5 % CO2. Determination of the minimum toxic concentration at which the cells remained alive was evaluated by morphological features (shape, monolayer integrity, adhesion to plastic). The study of the effect of pipsissewa extract on various cell functions was determined by the following methods: the ability to preserve morphological integrity - by the phase-contrast microscopy method, energy exchange - by the MTT test method, pinocytotic function - by the neutral red absorption method, migratory function - by the scratch test method, proliferative activity - by the doubling calculation method population Results. It is proposed to use concentrations of 0.05, 0.02, 0.01, 0.005 % of pipsissewa extract for further research. After carrying out the MTT reaction, the transition of MTT to formazan was confirmed microscopically in the negative control (native cells), at PE concentrations of 0.01 % and below, and the absence of a reaction in the positive control (cells killed by ethanol) at PE concentrations above 0.02 %. When recording the parameters of the NP absorption reaction, it was determined that PE at a concentration of 0.02 % and higher sharply suppresses pinocytotic activity, despite the partial preservation of cell adhesion, reducing the concentration by two times no longer affects mitochondria. A concentration of 0.01 % reduces proliferative activity, and at a concentration of 0.005 %, no difference with the control values ​​was found. Conclusions. When studying the assessment of the effect of pipsisewa extract on L929 cell culture, a toxic effect on these cells was established when added to the culture medium at a concentration above 0.01 %. The toxic effect had a threshold effect. Migratory and proliferative functions were the most sensitive, energy, pinocytosis and preservation of morphological integrity of cells were less sensitive

Troubled but in good hands: A qualitative study on patient experiences in diuresis renography examinations

IntroductionDiuresis renography is a nuclear medicine examination that can distinguish between obstructive and non-obstructive uropathy. Renography has been investigated before, but not from a patient perspective. The aim of this study was to gain knowledge and understanding of patient experiences with the diuresis renography process. MethodsThe study had a qualitative descriptive design; data was collected through semi-structured interviews with 17 adult patients that had recently undergone diuresis renography. The transcripts were analysed using inductive qualitative content analysis to identify their manifest and latent content. ResultsOne main theme was identified: ‘Not smooth all the way through, but still in good hands’. The participants understood the necessity of the performed renography and endured the examination despite its worrying elements. They were bothered by diuretic effects, worried about radioactivity and felt isolated during the imaging. The technologists' caring and informative approach eased their experience. The main theme was identified from three subthemes: ‘I experienced inconvenience’, ‘I was worried’ and ‘I felt safe’. ConclusionThe participants experienced worry throughout the renography process but were still satisfied with the examination, mostly because of the technologists being involved. Communication and interaction between patient and technologist are important for creating a good experience. Improved knowledge of patient experiences during renographies could be used to develop patient information and increase technologists’ awareness of factors patients may experience as troubling. Implications for practiceThis study describes issues that contribute to both negative and positive experiences. Improved professional awareness and knowledge about these issues can contribute to the development of patient information and professional encounters, and may improve patients’ compliance and overall experience.

Influence of substituted quinones on the excretory function of the rat kidney and evaluation of the prospects of their use as potential diuretics

Diuretics are widely used to treat pathologies of various genesis. However, the development of side effects during their long-term use remains a problem of traditional treatment regimens. The search for diuretics that would be aimed at inhibiting a key target molecule that is involved in the regulation of salt or water balance in the kidney, and certainly have a low level of toxicity and side effects, is an urgent task for researchers. Our preliminary screening of substituted quinones using in silico and in vitro methodology identified a number of effective compounds that outperform or compete with diuretics. The compounds are not "classic" carbonic anhydrase II inhibitors, but the pronounced diuretic effect of a number of compounds requires additional explanation. Therefore, the aim of the work was to study the effect of substituted quinones on the excretory function of rat kidneys to assess the prospects of their further structural modification and use as potential diuretics. Considering the experimental data, it should be noted that compounds AVD-6, AVD-7, AVD-8 and AVD-9 have pronounced diuretic activity. Thus, according to indicators of ex­cretory indices of electrolytes, it is possible to note the predominant influence of compounds AVD-6, AVD-7, AVD-8 and AVD-9 on excretion of sodium, potassium and chlorine from the body. Compounds AVD-6, AVD-7, AVD-8 and AVD-9, in contrast to Hydrochlorothiazide, which blocks carbonic anhydrase in the proximal part of the convoluted tubules and accelerates the excretion of potassium with from the urine, have a much lower excretory index as for these ions. Thus, our conducted research made it possible to identify a new, little-known class of hybrid molecular structures, namely (N'-(4-[(aroyloxy)imino]cyclohexa-2,5-dien-1-ylidene) aroylhydrazides (AVD-6, AVD-7, AVD-8 and AVD-9), which, in addition to affecting the excretory function of the kidneys, have significant diuretic activity and are potential diuretics.

Clinical Effect of the Traditional Japanese Herbal Medicine "Goreisan" on Water Balance in Patients With Severe Acute Pancreatitis.

Since severe acute pancreatitis (SAP) involves inflammatory mediators produced by local inflammation of the pancreas that trigger a systemic inflammatory response, intensive fluid management is required to maintain hemodynamics in the early stages of the onset of SAP. Goreisan is considered to have a diuretic effect in a state of excess water and an antidiuretic effect in a state of dehydration, regulating water balance in both directions. We investigated the clinical effects of Goreisan on water balance in SAP patients. Patients and methods: SAP patients admitted to our ICU within 72 hours of being diagnosed with SAP were divided into two groups: the Rikkunshito group (before October 2015) and theGoreisan group (after November 2015). Cumulative volume of fluid infusion, urine, fluid removal by CHF, nasogastric tube drainage, and water balance from day 1 to day 5 of ICU admission. Thirty patients were included. The median age was 57 (40-69) years, and 21/30 (70%) were male. The prognostic factor score in Japanese criteria for acute pancreatitis was 5.5 (3.3-7). Of the thirty patients, 14 were in the Rikkunshito group, and 16 were in the Goreisan group. There were no differences in the cumulative volume of fluid infusion, urine, fluid removal by CHF, or nasogastric tube drainage from day 1 to day 5 of ICU admission between the two groups. However, the cumulative water balance from day 1 to day 5 of admission was 4,957 ± 6,091 mL in the Rikkunshito group, whereas it was lower in the Goreisan group at 498 ± 3,918 mL (P = 0.023). Our study showed that Goreisan administration in patients with severe acute pancreatitis might improve water balance in the early phase of onset. Early administration of Goreisan at the onset of severe acute pancreatitis may regulate fluid movement between capillaries and interstitium and alleviate fluid overload due to water refill.

Phytochemical Profile of Eruca sativa and Its Therapeutic Potential in Disease Prevention and Treatment

Eruca sativa (E. sativa), commonly known as arugula, salad arugula, or simply arugula, is an annual plant species belonging to the Brassicaceae family. This leafy vegetable is widely cultivated for its edible leaves, characterized by a distinctive peppery flavor. The seeds are used for their rich fatty acid oils. This botanical specimen has been incorporated into various forms of traditional medicinal practices such as anti-inflammatory, depurative, diuretic, digestive, aphrodisiac, and rubefacient effects. The plant contains various bioactive compounds, including antioxidants, vitamins, minerals, carotenoids, glucosinolates, and flavonoids. This vegetable's broad therapeutic potential and diverse components are under ongoing research, enhancing our understanding of its medicinal properties. This review explores the phytochemical components of E. sativa and its efficacy in treating various diseases, offering a summary of its medicinal properties. Furthermore, it emphasizes the plant's importance in human health and suggests potential directions for future research in natural medicine.

Ayurvedic poisonous plants and their medicinal values

A poisonous plant is one that, when touched or consumed in large enough quantities, can be hazardous or lethal to humans or other animals. These plants can be utilized as herbal medicines with therapeutic effects when used in the right proportions and in small doses. Many plants are harmful to people when consumed or through skin contact with plant chemicals. Poisonous medicinal herbs are used to treat a variety of illnesses, including diabetes, cancer, infections, and fungal growth. According to the review, numerous phytochemical components that have diuretic, purgative, laxative, anti-allergic, and other significant therapeutic effects have been identified in a variety of medicinal plants. If utilized appropriately, poison can be life-giving, calming to the three Doshas, encouraging, and regenerating. The poisonous plants are categorized as Visha and Upvisha in Ayurvedic texts. Agadtantra is an important branch of Ashtanga Ayurveda. The importance of this branch has been described in our Vedas, Epics, and Samhita. Proper description, classification, clinical features, and management of any kind of Visha have been described in this branch. Some poisonous plants are Dhatura, Bhallataka, Vatsanabha, Bhanga, Vach, Kuchala, and Gunja, etc. The Shodhana process is the only bridge between Visha and Aushadhi. Shodhana is the process by which physical, chemical, and natural impurities are removed. It will intensify the potency and effectiveness of the drug and nullify its toxicity. The aim of this review article is to provide a brief overview of the numerous medicinal uses of some poisonous plants.

Association Between Serum Albumin and the Length of Hospital Stay Among Patients With Acute Heart Failure.

Introduction: Albumin plays a vital role in improving osmotic pressure and hemodynamics. A lower serum albumin level may cause pulmonary congestion and edema and contribute to myocardial dysfunction, diuresis resistance, and fluid retention in acute heart failure. Hypothesis: We hypothesized that AHF patients with normal serum albumin have shorter hospital stays. Methods: Using Electronic Medical Records, patients admitted from May 2020 through May 2021 aged >18, ICD-10, and positive Framingham Heart Failure Diagnostic Criteria were included. We excluded patients without albumin records and eGFRs less than 30mL/min/1.73m2. Prolonged hospitalization was defined as >8days of hospitalization. Results: During index emergency department visits, patients were symptomatic (New York Heart Association), aged median of 70years (Interquartile range (IQR) 18), 59% (n = 103) were male, predominantly White (73%, n = 128), and had a high Charleston Comorbidity index score [5, IQR (4-7)]. Nearly one-fourth (23%, n = 41) of the patients had <3.5g/dL albumin levels. The median length of hospital stay was eight days (IQR of 11). Comparing differences between lengths of hospital stays (<8 vs. >8 days), there was different serum albumin (3.9 + 0.48 vs. 3.6 + 0.53, p < .001) and left ventricular ejection fraction (45% (range 26-63) versus 30% (range 24-48), p = .004). An increased serum albumin decreased prolonged hospitalization (odds ratio (OR), 0.28; 95% confidence interval (CI), 0.14-0.55, p = <0.001). Patients in the lower albumin group had higher NT-proBNP (median: 8521 (range 2025-9134) versus 5147 (range 2966-14,795) pg/ml, p = .007) and delay in administering intravenous diuretics (391 (167-964) minutes versus 271 (range 157-533) minutes, p = .02). Conclusion: Hypoalbuminemia is strongly associated with prolonged hospitalization. Timely and effective diuretic therapy may reduce hospital stay durations, particularly with albumin supplementation.

The acute effects of furosemide in acute heart failure assessed by remote dielectric sensing. A protocol.

Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs. This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward. Remote dielectric sensing (ReDS) will directly measure lung fluid content, and cardiac filling pressures will be assessed by echocardiography with Doppler and strain analysis. This study will examine if furosemide leads to a hyperacute reduction in pulmonary congestion assessed by ReDS independent of diuretic effects in patients with AHF. We hypothesise that the haemodynamic effect of furosemide shown on pulmonary congestion may explain the subjective instant relief in patients with AHF receiving furosemide. Dr. Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by the Danish Heart Foundation. This protocol was approved by the Scientific Ethical Committee, H-23029822, and the Danish Data Protection Agency P-2013-14703. The protocol was registered with ClinicalTrial.org on 29 August 2023 (Identifier: NCT06024889).

Acetazolamide Tolerance in Acute Decompensated Heart Failure: An Observational Study

Objectives: This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve decongestion in the context of patients hospitalized for acute heart failure (HF). However, data in terms of safety are lacking. Methods: We conducted a monocentric observational prospective study from November 2023 to February 2024 in a 12-bed cardiology department, recording adverse events (hypotension, severe metabolic acidosis, severe hypokalemia and renal events) during in-hospital HF treatment. All patients hospitalized for acute HF during the study period treated with ACZ (500 mg IV daily for 3 days) on top of IV furosemide (n = 28, 48.3%) were compared with patients who have been treated with IV furosemide alone (n = 30, 51.7%). Results: The patients treated with ACZ were younger than those without (median age 78 (range 67–86) vs. 85 (79–90) years, respectively, p = 0.01) and had less frequent chronic kidney disease (median estimated glomerular fraction rate (60 (35–65) vs. 38 (26–63) mL/min, p = 0.02). As concerned adverse events during HF treatment, there were no differences in the occurrences of hypotension (three patients [10.7%] in the ACZ group vs. four [13.3%], p = 0.8), renal events (four patients [14.3%] in the ACZ group vs. five [16.7%], p = 1) and severe hypokalemia (two [7.1%] in the ACZ group vs. three [10%], p = 1). No severe metabolic acidosis occurred in either group. Conclusions: Although the clinical characteristics differed at baseline, with younger age and better renal function in patients receiving ACZ, the tolerance profile did not significantly differ from patients receiving furosemide alone. Additional observational data are needed to further assess the safety of ACZ–furosemide combination in the in-hospital management of HF, especially in older, frail populations.

Cannabinoid receptor type 1 activation causes a water diuresis by inducing an acute central diabetes insipidus in mice.

Cannabis and synthetic cannabinoid consumption are increasing worldwide. Cannabis contains numerous phytocannabinoids that act on the G protein-coupled cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 expressed throughout the body, including the kidney. Essentially every organ, including the kidney, produces endocannabinoids, which are endogenous ligands to these receptors. Cannabinoids acutely increase urine output in rodents and humans, thus potentially influencing total body water and electrolyte homeostasis. As the kidney collecting duct (CD) regulates total body water, acid/base, and electrolyte balance through specific functions of principal cells (PCs) and intercalated cells (ICs), we examined the cell-specific immunolocalization of CB1R in the mouse CD. Antibodies against either the C-terminus or N-terminus of CB1R consistently labeled aquaporin 2 (AQP2)-negative cells in the cortical and medullary CD and thus presumably ICs. Given the well-established role of ICs in urinary acidification, we used a clearance approach in mice that were acid loaded with 280 mM NH4Cl for 7 days and nonacid-loaded mice treated with the cannabinoid receptor agonist WIN55,212-2 (WIN) or a vehicle control. Although WIN had no effect on urinary acidification, these WIN-treated mice had less apical + subapical AQP2 expression in PCs compared with controls and developed acute diabetes insipidus associated with the excretion of large volumes of dilute urine. Mice maximally concentrated their urine when WIN and 1-desamino-8-d-arginine vasopressin [desmopressin (DDAVP)] were coadministered, consistent with central rather than nephrogenic diabetes insipidus. Although ICs express CB1R, the physiological role of CB1R in this cell type remains to be determined.NEW & NOTEWORTHY The CB1R agonist WIN55,212-2 induces central diabetes insipidus in mice. This research integrates existing knowledge regarding the diuretic effects of cannabinoids and the influence of CB1R on vasopressin secretion while adding new mechanistic insights about total body water homeostasis. Our findings provide a deeper understanding about the potential clinical impact of cannabinoids on human physiology and may help identify targets for novel therapeutics to treat water and electrolyte disorders such as hyponatremia and volume overload.

Tolvaptan therapy for edema in patients with chronic kidney disease.

Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p<0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.