The Effectiveness of Albumin Combined with Diuretics in Treating Ascites in Cirrhosis

Cirrhosis often leads to various complications during its progression,with ascites being one of the most common.Among these cases,5%to 10%are classified as refractory ascites.In recent years,clinical research on the treatment of cirrhotic ascites has yielded increasingly enriched results.In this paper,a large number of clinical data on the treatment of ascites using albumin combined with diuretics were collected,and it was found that there were more results in group control studies.It was believed that albumin combined with diuretic therapy could effectively improve symptoms,reduce the occurrence of adverse reactions,ensure the safety of patients,and have a good clinical application prospect.This paper reviews the efficacy of albumin combined with diuretics in the treatment of ascites in cirrhosis.

Effects of Different Diuretics on Water Drinking Amount, Urination Volume and Related Blood Indices of Sheep Fed with Cottonseed

[Objective] This study aimed to investigate the effects of three kinds of diuretics on the water drinking amount and urination volume of sheep fed with cottonseed hulls. [Method] The method of self-control was adopted. Five two-year-old male Kazak sheep about 40 kg which never had intake of the feeds containing gossypol were selected. The experiment was divided into five periods, namely the control period, a period with the supplement of 300 mg/d of hydrochlorothiazide, a period with the supplement of 200 mg/d of hydrochlorothiazide, a period with the supplement of 350 mg of GY-01 and a period with the supplement of 200 mg of GY-01. The sheep were fed with the concentrate and the cottonseed hulls in the control period, and corresponding diuretics were supplemented in the rest four periods. The water drinking amount, urination volume and the contents of the hormone and ion in the blood were determined in each period. [Result] After 350 mg GY-01 was supplemented, the water drinking amount of each sheep had an increase of 60.14% compared with that of the sheep in the control period and the urination volume was 2.67 times of that of the latter, and the differences were both significant （P0.01）. The antidiuretic hormone declined by 32.59% compared with that of the sheep in the control period, with the significant difference （P 0.05）. The adrenocorticotropic hormone content increased by 81.93% compared with that of the sheep in the control period and the difference was significant （P0.01）. An increase of 28.04% （P 0.05） and 39.39% （P 0.01） was found in the contents of serum potassium and phosphorus respectively compared with that of sheep in the control period. [Conclusion] The diet with supplement of GY-01 can increase the urination volume of livestock fed with the cottonseed hulls, and the most appropriate supplement amount is 200 mg GY-01.

Ototoxic effects and mechanisms of loop diuretics

Over the past two decades considerable progress has been made in understanding the ototoxic effects and mechanisms underlying loop diuretics. As typical representative of loop diuretics ethacrynic acid or furosemide only induces temporary hearing loss, but rarely permanent deafness unless applied in severe acute or chronic renal failure or with other ototoxic drugs. Loop diuretic induce unique pathological changes in the cochlea such as formation of edematous spaces in the epithelium of the stria vascularis, which leads to rapid decrease of the endolymphatic potential and eventual loss of the cochlear microphonic potential, summating potential, and compound action potential. Loop diuretics interfere with strial adenylate cyclase and Nat/Kt-ATPase and inhibit the Na-K-2Cl cotransporter in the stria vascularis, however recent reports indicate that one of the earliest effects in vivo is to abolish blood flow in the vessels supplying the lateral wall. Since ethacrynic acid does not damage the stria vascularis in vitro, the changes in Nat/Kt-ATPase and Na-K-2Cl seen in vivo may be secondary effects results from strial ischemia and anoxia. Recent observations showing that renin is present in pericytes surrounding stria arterioles suggest that diuretics may induce local vasoconstriction by renin secretion and angiotensin formation. The tight junctions in the blood-cochlea barrier prevent toxic molecules and pathogens from entering cochlea, but when diuretics induce a transient ischemia, the barrier is temporarily disrupted allowing the entry of toxic chemicals or pathogens.

The use of diuretics in acute heart failure: Evidence based therapy?

The evidence base for the use of diuretics in acute heart failure is limited, with no large double-blind placebo-controlled randomized trials. However, their use as a first line treatment of acute heart failure is firmly established in clinical practice, and endorsed in clinical guidelines. Loop diuretics are typically the first line diuretic strategy for the treatment of acute heart failure. For patients with considerable fluid retention, there is some evidence that initial treatment with continuous infusion or boluses of high dose loop diuretic is superior to an initial lower dose strategy. In patients who are diuretic resistant, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. Intravenous low-dose dopamine has also been used to assist diuresis and preserve renal function in such circumstances, but trials are underway to confirm the clinical value of this agent. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence base is not secure, and its place in clinical practice is yet to be established.

Determination of 8 Diuretics and Probenecid in Human Urine by Gas Chromatography-Mass Spectrometry: Confirmation Procedure

A fast and sensitive method for determination of 8 diuretics (acetazolamide, bendroflumethiazide, bumetanide, chlorthalidone, furosemide, hydrochlorothiazide, metolazone, triamterene) and masking agent (probenecid) in human urine using gas-chromatography with mass spectrometric detection is described. The extraction of the substances as function of the nature of organic solvent, mixing time and pH of aqueous phase was studied. The tandem mass spectrometry was used to increase selectivity of diuretics determination due to elimination of background interferences. Fragmentation reactions were studied for each compound and their collision energies were optimized to obtain the best selectivity. The results of method’s validation demonstrate its suitability in routine analysis for confirmation purposes.

Urea transporter inhibitors identified as novel diuretics

Urea transporters （UT）, including isoforms of UT-A endothelia and erythrocytes, play an important role in the urine in kidney tubule epithelia and UT-B in vasa recta concentration mechanism by mediated an intrarenalurea recycling, suggesting that functional inhibition of these proteins could have therapeutic use as diuretic. By in- tegrated cell based high throughput screening and in silico methods, a class of small-molecule drug-like compounds with thienoquinolin core structure was found to have inhibition activity on both UT-A and UT-B. The structure and activity relationship analysis showed a compound PU-48, named chemically as methyl 3-amino-6-methoxythieno[ 2, 3-b] quinoline-2-carboxylate, had the best UT-A and UT-B inhibition activity. IC50s of PU-48 on UT-B facilitated as determined by erythrocyte lysis assay. In vivo urea transport were micromole level in human, rat, and mouse, activity of PU-48 on urinary concentrating function was evaluated in rats fed ad libitum in metabolic cages. Urine output significantly increased in a dose-dependent manner in rats subcutaneously administered PU-48. Urinary os- molality and urea concentration were significantly decreased. The peak changes of urine output, urinary osmolality and urinary urea concentration occurred between 2 and 4 h after PU/18 administration, with values returning to was subcutaneously injected every 6 h the 24 h urine output in baseline by 10 h. When PU-48 at 50 mg · kg^-1 PU-48 treated rats was significantly higher than that in vehicle control rats. Urinary osmolality and urea concentra- tion in PU-48 treated rats were significantly lower than in vehicle control rats. The excretion of Na ＋ , K ＋ , C1- was PU-48 treated rats had significantly higher urea excre- similar in PU-48 treated and vehicle control rats. However, tion than vehicle control rats. The data suggest that PU-48 caused a urea-selective diuresis without disturbing elec- TGs, and LDL-C in PU-48-treated rats were similar with those trolyte metabolism. Notably, blood urea, T-CHO, in vehicle control rats, which are normal levels. These data indicate that the diuretic effect of PU-14 does not cause electrolyte imbalance and abnormal metabolism. It is predicated that UT inhibitors have potential clinical applica- tions as sodium-sparing diuretics in edema from different etiologies, such as congestive heart failure and cirrhosis.

GC-MS STUDY ON DIURETICS IN URINE Ⅱ.DETECTION METHOD USING TRIMETHYLSILYLATION

A reliable method is described for the detection of amitoride,triamterene. canrenone and spironolactone in human urine using GC-MS analysis after trimethytsitytation.The mass spectrometric and metabotic features of the compounds are discussed

GC-MS STUDY ON DIURETICS IN URINE Ⅰ.BETECTION METHOD USING METHYLATION

A reliable and sensitive method is developed for the detection of common diuretics in human urine. diuretics along with probenecid are methylated and subjected to GC-MS analysis.Both chromatographic and mass spectrometric data are obtained in selected ion monitoring and full scanning modes.The average detection limit is 0.1-1.0 ag/mi urine.This method is suitable to large-scale and routine screening or confirmation of diuretics in doping control.

The Effect of Loop Diuretics on Sarcopenia and Long-Term Prognosis in Patients with Refractory Hepatic Ascites Treated with Tolvaptan

We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese version of the Support Team Assessment Schedule. The psoas muscle index (PMI) was used to define sarcopenia. A statistically significant difference was observed in the PMI between patients receiving low-dose (3.6 ± 1.2 cm2/m2) and high-dose furosemide (3.1 ± 1.2 cm2/m2) before tolvaptan treatment (P = 0.048). The PMI increased from 3.2 ± 1.1 cm2/m2 to 3.5 ± 1.3 cm2/m2 (P = 0.002) in responders, but decreased from 3.4 ± 1.2 cm2/m2 to 3.0 ± 1.0 cm2/m2 (P = 0.106) in non-responders before and after tolvaptan treatment, respectively. The long-term prognosis improved in responders compared with non-responders (mean survival time: 646 days vs. 228 days, P < 0.001). Early introduction of tolvaptan treatment is necessary to prevent the progression of sarcopenia.

Effects of Three Commonly-used Diuretics on the Urinary Proteome

Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics （furosemide, F; hydrochlorothiazide, H; and spirolactone, S） on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography-tandem mass spectrometry （LC-MS/MS）. Based on the criteria of P ≤ 0.05, a fold change ≥2, a spectral count ≥ 5, and false positive rate （FDR） ≤1%, 14 proteins （seven for F, five for H, and two for S） were identified by Progenesis LC-MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.

Discovery of novel diarylamides as orally active diuretics targeting urea transporters

Urea transporters(UT)play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics.Thus,UT inhibitors are promising for development as novel diuretics.In the present study,a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening.Optimization of the inhibitor led to the identifi-cation of a promising preclinical candidate,N-[4-(acetylamino)phenyl]-5-nitrofuran-2-carboxamide(1 H),with excellent in vitro UT inhibitory activity at the submicromolar level.The half maximal inhibitory concentrations of 1 H against UT-B in mouse,rat,and human erythrocyte were 1.60,0.64,and0.13 mmol/L,respectively.Further investigation suggested that 8 mmol/L 1 H more powerfully inhibited UT-A1 at a rate of 86.8%than UT-B at a rate of 73.9%in MDCK cell models.Most interestingly,we found for the first time that oral administration of 1 H at a dose of 100 mg/kg showed superior diuretic effect in vivo without causing electrolyte imbalance in rats.Additionally,1 H did not exhibit apparent toxicity in vivo and in vitro,and possessed favorable pharmacokinetic characteristics.1 H shows promise as a novel diuretic to treat hyponatremia accompanied with volume expansion and may cause few side effects.

Prognostic Factors in Cardiorenal Syndrome Type 1: Retrospective Observational and Analytical Study

Introduction: Type 1 cardiorenal syndrome (CRS 1) is characterized by acute impairment of cardiac function leading to acute renal dysfunction. CRS1 is present in 25% of patients admitted for heart failure. The objective of our study is to analyze the epidemiological, clinical, therapeutic profile and the risk and prognostic factors of these patients. Materials and Methods: We identified 120 patients with cardiorenal syndrome (CRS) over a one-year period to determine the prevalence and risk factors for developing CRS 1. We analyzed the clinical, biological, and evolutionary profiles of patients with CRS 1 and determined the risk factors for the occurrence of acute kidney injury (AKI) as well as the mortality factors in these patients. Résultats: The average age of our patients with CRS1 is 58 ± 9 years, with a sex ratio of 1.4. The average eGFR of our patients is 35 ± 6.5 ml/min/1.73m2. Diabetes was found in 17% of our patients and hypertension in 14%. The etiology of cardiac impairment is predominantly acute coronary syndrome (ACS), followed by rhythm disorders. Renally, all our patients have acute kidney injury (AKI), with 86% having functional acute renal failure and 14% having acute tubular necrosis. Therapeutically, 50% of our patients are on diuretics, 42% receive beta-blocker treatment, and RAAS blockers are used in 29% of cases. Renal replacement therapy (RRT) sessions were required in 13.8% of cases. In univariate analysis, male gender, tachyarrhythmia, and hypertension are associated with the early onset of acute kidney injury (AKI). The use of diuretics, anemia, and low left ventricular ejection fraction (LVEF) are linked to a higher risk of developing CRS 1 (p = 0.021, p = 0.037, p = 0.010 respectively). In multivariate analysis, advanced age is significantly associated with increased mortality risk in CRS 1 patients (p = 0.030), while beta-blocker use is considered a protective factor (p = 0.014). Conclusion: Our study identifies several key factors associated with outcomes in type 1 CRS. Male gender, tachyarrhythmia, and hypertension are linked to early-onset AKI. The use of diuretics and the presence of anemia increase the risk of developing CRS1. Advanced age is significantly associated with higher mortality rates. Conversely, the use of beta-blockers appears to be protective in this patient population. .

Congestive Heart Failure: Treatment of Symptoms or Causes

This paper is based on the author’s 20+ years of experience treating patients with congestive heart failure (CHF) as a cardiologist. In the 20+ years, 64 patients were treated, including both with reduced and preserved left ventricular function. Most patients had a 4 - 5 days hospitalization in their first admission with one readmission (1.6%) over seven years. This paper will help us understand the physiology and pathophysiology of congestive heart failure, especially how to use beta blockers and diuretics. It will shorten the length of hospitalization and lower the readmission rate and cost of CHF treatment. This paper will help us to open another research direction for CHF.

Hypokalemia Havoc: Unraveling the Mystery of Unexplained Potassium Depletion

Hypokalemia, defined as serum potassium below 3.5 mEq/L, can lead to severe complications such as arrhythmias and muscle paralysis, potentially resulting in rhabdomyolysis. The etiology of hypokalemia is often multifactorial, involving but not limited to gastrointestinal losses, renal losses, medication effects, and inadequate dietary intake. Chronic heavy alcohol use, obstructive sleep apnea (OSA), and the use of diuretics such as hydrochlorothiazide (HCTZ) are also significant contributing factors. Effective management requires thorough evaluation and investigation to effectively treat a patient. This case report aims to illustrate the diagnostic challenges and comprehensive treatment approach required in a patient with multiple comorbidities and severe hypokalemia, emphasizing the need for a multidisciplinary and comprehensive approach to address all underlying causes.

人尿中美托拉宗的液相色谱-质谱研究

A sensitive and reliable procedure for analysis of metolazone in human urine by HPLC-MS was describes.The extraction recovery of liquid-liquid extraction (LLE) at various pH were studied.The detection limit of the compound was below 0.2ng at absolute amount.It is suitable for metolazone screening and confirmation in doping control.

Diagnosis and therapy of ascites in liver cirrhosis

Ascites is one of the major complications of liver cirrhosis and is associated with a poor prognosis. It is important to distinguish noncirrhotic from cirrhotic causes of ascites to guide therapy in patients with noncirrhotic ascites. Mild to moderate ascites is treated by salt restriction and diuretic therapy. The diuretic of choice is spironolactone. A combination treatment with furosemide might be necessary in patients who do not respond to spironolactone alone. Tense ascites is treated by paracentesis, followed by albumin infusion and diuretic therapy. Treatment options for refractory ascites include repeated paracentesis and transjugular intrahepatic portosystemic shunt placement in patients with a preserved liver function. Potential complications of ascites are spontaneous bacterial peritonitis (SBP) and hepatorenal syndrome (HRS). SBP is diagnosed by an ascitic neutrophil count > 250 cells/mm3 and is treated with antibiotics. Patients who survive a first episode of SBP or with a low protein concentration in the ascitic fluid require an antibiotic prophylaxis. The prognosis of untreated HRS type 1 is grave. Treatment consists of a combination of terlipressin and albumin. Hemodialysis might serve in selected patients as a bridging therapy to liver transplantation. Liver transplantation should be considered in all patients with ascites and liver cirrhosis.

Current approaches to the management of patients with cirrhotic ascites

This review describes current approaches to the management of patients with cirrhotic ascites in relation to the severity of its clinical manifestations. The PubMed database, the Google Scholar retrieval system, the Cochrane Database of Systematic Reviews, and the reference lists from related articles were used to search for relevant publications. Articles corresponding to the aim of the review were selected for 1991-2018 using the keywords:“liver cirrhosis,”“portal hypertension,”“ascites,”“pathogenesis,”“diagnostics,” and “treatment.” Uncomplicated and refractory ascites in patients with cirrhosis were the inclusion criteria. The literature analysis has shown that despite the achievements of modern hepatology, the presence of ascites is associated with poor prognosis and high mortality. The key to successful management of patients with ascites may be the stratification of the risk of an adverse outcome and personalized therapy. Pathogenetically based approach to the choice of pharmacotherapy and optimization of minimally invasive methods of treatment may improve the quality of life and increase the survival rate of this category of patients.

Current and future pharmacological therapies for managing cirrhosis and its complications

Due to the restrictions of liver transplantation,complication-guided pharmacological therapy has become the mainstay of long-term management of cirrhosis.This article aims to provide a complete overview of pharmacotherapy options that may be commenced in the outpatient setting which are available for managing cirrhosis and its complications,together with discussion of current controversies and potential future directions.PubMed/Medline/Cochrane Library were electronically searched up to December 2018 to identify studies evaluating safety,efficacy and therapeutic mechanisms of pharmacological agents in cirrhotic adults and animal models of cirrhosis.Non-selective betablockers effectively reduce variceal re-bleeding risk in cirrhotic patients with moderate/large varices,but appear ineffective for primary prevention of variceal development and may compromise renal function and haemodynamic stability in advanced decompensation.Recent observational studies suggest protective,haemodynamically-independent effects of beta-blockers relating to reduced bacterial translocation.The gut-selective antibiotic rifaximin is effective for secondary prophylaxis of hepatic encephalopathy;recent small trials also indicate its potential superiority to norfloxacin for secondary prevention of spontaneous bacterial peritonitis.Diuretics remain the mainstay of uncomplicated ascites treatment,and early trials suggest alpha-adrenergic receptor agonists may improve diuretic response in refractory ascites.Vaptans have not demonstrated clinical effectiveness in treating refractory ascites and may cause detrimental complications.Despite initial hepatotoxicity concerns,safety of statin administration has been demonstrated in compensated cirrhosis.Furthermore,statins are suggested to have protective effects upon fibrosis progression,decompensation and mortality.Evidence as to whether proton pump inhibitors cause gut-liver-brain axis dysfunction is conflicting.Emerging evidence indicates that anticoagulation therapy reduces incidence and increases recanalisation rates of non-malignant portal vein thrombosis,and may impede hepatic fibrogenesis and decompensation.Pharmacotherapy for cirrhosis should be implemented in accordance with up-to-date guidelines and in conjunction with aetiology management,nutritional optimisation and patient education.

Thiazide-associated hyponatremia in the elderly： what the clinician needs to know

Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malignancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antide- pressants. Sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clini- cians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clinical and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inap- propriate antidiuretic hormone secretion （SIADH）. The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides （extracellular volume depletion-related or SIADH-like）. Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.

Twenty-four-hour ambulatory blood pressure changes in older patients with essential hypertension receiving monotherapy or dual combination antihypertensive drug therapy

Objective To evaluate the differences in 24-hour ambulatory blood pressure (BP) in older patients with hypertension treated with the five major classes of antihypertensive drugs,as monotherapy or dual combination therapy,to improve daytime and nighttime BP control. Methods We enrolled 1920 Chinese community-dwelling outpatients aged ≥ 60 years and compared ambulatory BP values and ambulatory BP control (24-hour BP < 130/80 mmHg;daytime mean BP < 135/85 mmHg;and nighttime mean BP < 120/70 mmHg),as well as nighttime BP dip patterns for monotherapy and dual combination therapy groups. Results Patients’ mean age was 71 years,and 59.5% of patients were women. Calcium channel blockers (CCBs) constituted the most common (60.3% of patients) monotherapy,and renin–angiotensin system (RAS) blockers combined with CCBs was the most common (56.5% of patients) dual combination therapy. Monotherapy with beta-blockers (BB) provided the best daytime BP control. The probabilities of having a nighttime dip pattern and nighttime BP control were higher in patients receiving diuretics compared with CCBs (OR = 0.52,P = 0.05 and OR = 0.41,P = 0.007,respectively). Patients receiving RAS/diuretic combination therapy had a higher probability of having controlled nighttime BP compared with those receiving RAS/CCB (OR = 0.45,P = 0.004). Compared with RAS/diuretic therapy,BB/CCB therapy had a higher probability of achieving daytime BP control (OR = 1.27,P = 0.45). Conclusions Antihypertensive monotherapy and dual combination drug therapy provided different ambulatory BP control and nighttime BP dip patterns. BB-based regimens provided lower daytime BP,whereas diuretic-based therapies provided lower nighttime BP,compared with other antihypertensive regimens.