Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Men are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women. Previous studies suggest that greater urine concentration is associated with acceleration of progression of chronic kidney disease (CKD), increased urinary albumin excretion, and delayed renal sodium excretion. The present review addresses possible sex-related differences in urine volume and osmolality (U(osm)) that could participate in this male risk predominance. Because of the scarcity of information, we reanalyzed 24-h urine data collected previously by different investigators for other purposes. In nine studies concerning healthy subjects (6 studies) or patients with CKD or diabetes mellitus, U(osm) (or another index of urine concentration based on the urine/plasma creatinine concentration ratio) was 21-39% higher (i.e., about a 150 mosm/kgH2O difference) in men than in women. Urine volume was not statistically different. Thus, the larger osmolar load of men (related to their higher food intake) is excreted in a more concentrated urine with no difference in urine volume. This sex difference was not influenced by the level of sodium excretion and was still present in CKD patients. Sex differences in thirst threshold, AVP level, and other regulatory mediators may all contribute to the higher male U(osm). Because of the previously demonstrated adverse effects of vasopressin and/or high urine concentrating activity, the greater tendency of men to concentrate urine could participate in their greater susceptibility to urolithiasis and hypertension and to the faster progression towards end-stage renal failure.
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PMID:Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease. 1699 Apr 87

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease that causes kidney failure and accounts for 10% of all patients who are on renal replacement therapy. However, the marked phenotypic variation between patients who carry the same PKD1 or PKD2 mutation suggests that nonallelic factors may have a greater influence on the cystic phenotype. Endothelin-1 (ET-1) transgenic mice have been reported to develop profound renal cystic disease and interstitial fibrosis without hypertension. The hypothesis that ET-1 acts as a modifying factor for cystic disease progression was tested in an orthologous mouse model of ADPKD (Pkd2(WS25/-)). Four experimental groups (n = 8 to 11) were treated from 5 to 16 wk of age with the highly selective orally active receptor antagonists ABT-627 (ETA) and A-192621 (ETB) singly or in combination. Unexpected, ETB blockade led to accelerated cystic kidney disease. Of significance, this was associated with a reduction in urine volume and sodium excretion and increases in urine osmolarity and renal cAMP and ET-1 concentrations. The deleterious effect of chronic ETB blockade was neutralized by simultaneous ETA blockade. ETA blockade alone resulted in a significant increase in tubular cell proliferation but did not alter the cystic phenotype. It is concluded that the balance between ETA and ETB signaling is critical for maintaining tubular structure and function in the cystic kidney. These results implicate ET, acting via vasopressin-dependent and independent pathways, as a major modifying factor for cystic disease progression in human ADPKD.
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PMID:Endothelin B receptor blockade accelerates disease progression in a murine model of autosomal dominant polycystic kidney disease. 1720 12

Ascites, the most common complication of cirrhosis, is associated with a poor quality of life, an increased risk of infection, and renal failure. Twenty percent of cirrhotic patients have ascites at the time of diagnosis, while 30% and 50% will develop ascites by 5 and 10 years, respectively. There are several factors that contribute to ascites formation in cirrhotic patients, these include splanchnic vasodilatation, arterial hypotension, high cardiac output, and decreased vascular resistance. These factors lead to ineffective intravascular volume (hyperdynamic state), impairment of renal function, and subsequent water and sodium retention, all of which lead to dilutional hyponatremia (serum sodium <130 mEq/L), one of the most important prognostic factors in these patients. In conclusion, the therapeutic objective is to improve sodium balance and circulatory function through non-pharmacological measures, such as dietary sodium and water restriction as well as bed rest. Spironolactone (100-400 mg/day) is the initial drug of choice, while loop diuretics (like furosemide, 40-60 mg/day) are frequently used as adjuvants. Recently, agent that interfere with the renal effects of vasopressin by inhibiting water reabsorption in collecting ducts and producing free water diuresis have been used. These agents are called aquaretics and can be useful in the treatment o ascites unresponsive to conventional therapy.<br />
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PMID:Pathophysiology of ascites and dilutional hyponatremia: contemporary use of aquaretic agents. 1800 50

Polycystic kidney diseases (autosomal dominant and autosomal recessive) are progressive renal tubular cystic diseases, which are characterised by cyst expansion and loss of normal kidney structure and function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common life- threatening, hereditary disease. ADPKD is more prevalent than Huntington's disease, haemophilia, sickle cell disease, cystic fibrosis, myotonic dystrophy and Down's syndrome combined. Early diagnosis and treatment of hypertension with inhibitors of the renin-angiotensin-aldosterone system (RAAS) and its potential protective effect on left ventricular hypertrophy has been one of the major therapeutic goals to decrease cardiac complications and contribute to improved prognosis of the disease. Advances in the understanding of the genetics, molecular biology and pathophysiology of the disease are likely to facilitate the improvement of treatments for these diseases. Developments in describing the role of intracellular calcium ([Ca(2+)](i)) and its correlation with cellular signalling systems, Ras/Raf/mitogen extracellular kinase (MEK)/extracellular signal-regulated protein kinase (ERK), and interaction of these pathways with cyclic adenosine monophosphate (cAMP) levels, provide new insights on treatment strategies. Blocking the vasopressin V(2) receptor, a major adenylyl cyclase agonist, demonstrated significant improvements in inhibiting cytogenesis in animal models. Because of activation of the mammalian target of rapamycin (mTOR) pathway, the use of sirolimus (rapamycin) an mTOR inhibitor, markedly reduced cyst formation and decreased polycystic kidney size in several animal models. Caspase inhibitors have been shown to decrease cytogenesis and renal failure in rats with cystic disease. Cystic fluid secretion results in cyst enlargement and somatostatin analogues have been shown to decrease renal cyst progression in patients with ADPKD. The safety and efficacy of these classes of drugs provide potential interventions for experimental and clinical trials.
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PMID:Potential pharmacological interventions in polycystic kidney disease. 1803 88

Accumulation of fluid as ascites is the most common complication of cirrhosis. This is occurring in about 50% of patients within 10 years of the diagnosis of cirrhosis. It is a prognostic sign with 1-year and 5-year survival of 85% and 56%, respectively. The most acceptable theory for ascites formation is peripheral arterial vasodilation leading to underfilling of circulatory volume. This triggers the baroreceptor-mediated activation of renin-angiotensin-aldosterone system, sympathetic nervous system and nonosmotic release of vasopressin to restore circulatory integrity. The result is an avid sodium and water retention, identified as a preascitic state. This condition will evolve in overt fluid retention and ascites, as the liver disease progresses. Once ascites is present, most therapeutic modalities are directed on maintaining negative sodium balance, including salt restriction, bed rest and diuretics. Paracentesis and albumin infusion is applied to tense ascites. Transjugular intrahepatic portosystemic shunt is considered for refractory ascites. With worsening of liver disease, fluid retention is associated with other complications; such as spontaneous bacterial peritonitis. This is a primary infection of ascitic fluid caused by organisms originating from large intestinal normal flora. Diagnostic paracentesis and antibiotic therapy plus prophylactic regimen are mandatory. Hepatorenal syndrome is a state of functional renal failure in the setting of low cardiac output and impaired renal perfusion. Its management is based on drugs that restore normal renal blood flow through peripheral arterial and splanchnic vasoconstriction, renal vasodilation and/or plasma volume expansion. However, the definitive treatment is liver transplantation.
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PMID:Fluid retention in cirrhosis: pathophysiology and management. 1818 68

The failing heart produces a variety of biologically active humoral factors such as catecholamines, vasopressin, angiotensin II, aldosterone, atrial natriuretic polypeptide (ANP), brain natriuretic polypeptide (BNP), cytokines and so on, in order to recover the cardiac function through the mechano- and chemo-receptors in vivo. In particular, it has recently shown that the central nervous system plays a pivotal role in the progression of cardiac remodeling and the heart failure. Thereby, endogenous digitalis-like factor, angiotensisn II, aldostereone, and inflammatory cytokines in the brain are acting as the mediators. In fact, mineralocorticoid receptor blockers, such as spironolactone and eplerenone, are clinically useful to treat cardiac failure. However, these biomarkers are not available as laboratory tests because they are under investigation clinically. On the other hand, failing heart by itself produces natriuretic hormones such as ANP and BNP to rescue it. They dilate resistant vessels to reduce the afterload of the heart with the lowest concentrations. Then, natriuresis is caused with the increased concentrations to reduce the pre-load to the heart. The natriuresis is brought partially by reducing concentrations of plasma aldosterone. Therefore, concentrations of these natriuretic hormones are excellent biomarkers for the cardiac function. They increase in a variety of disease states like hypertension, acute/old myocardial infarction, angina pectoris, arrhythmias, cardiac failure, cardiomyopathy, renal failure and myocarditis. In particular, they are remarkably increased in patients with heart failure. Recently, a new biomarker, N-terminal pro-BNP (NT-proBNP) is registered as a clinically available laboratory test, which may be superior to BNP at the laboratory stand of view. It is because NT proBNP is not degraded in the circulation, stable even in serum and the higher concentration as compared to BNP.
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PMID:[Pathophysiology of heart failure and the biomarkers; brain natriuretic hormone as the class-1 recommendation by the new Japanese Guideline for Heart Failure]. 1828 62

Hepato-renal syndrome (HRS) is a functional renal failure complicating end-stage liver disease. HRS is characterized by marked arterial vasodilation (mainly of the splanchnic bed) and severe renal vasoconstriction. HRS is classified into 2 types: type I HRS shows a rapid and progressive decline in renal function with a very poor prognosis (median survival of about 2 weeks); HRS type 2 has a more stable renal failure, with a median survival of about 6 months. The management of HRS is still a big challenge. The definitive therapy for HRS is liver transplantation (LT); however, the survival rate of HRS patients is poor, and important organ shortage exists. Various approaches have been used for HRS treatment including vasoconstrictor therapy. Recent evidence has shown that vasoconstrictor agents are effective and serve as a bridge to LT; the rationale for vasoconstrictors is to counteract the splanchnic arterial vasodilation and increase the effective arterial blood volume. Thus, renal perfusion and glomerular filtration rates improve. Terlipressin, a V1 vasopressin agonist, has been used frequently. A recent meta-analysis of clinical trials showed that the pooled rate of patients who reversed HRS after terlipressin therapy was 0.52 (95% CI, 0.42; 0.61; P = 0.0001, /2 = 24.6%). The pooled Odds Ratio (OR) for mortality rate in HRS patients who were not responders to terlipressin versus responders was 5.746 (95% CI, 1.5; 21.9; P = 0.0005). Prospective, controlled clinical trials are in progress to address the impact of vasoconstrictor use on survival in HRS patients. Alternative therapies such as transjugular intrahepatic portosystemic shunts (TIPS) and extracorporeal albumin dialysis (ECAD) have given encouraging results but experience is extremely limited.
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PMID:Recent advances in the management of hepato-renal syndrome (HRS). 1828 7

Ascites is the most common complication of cirrhosis and is associated with an increased risk for the development of infections, dilutional hyponatremia, renal failure, and mortality. Cirrhotic patients who develop ascites and associated complications have a low probability of long-term survival without liver transplantation, and therefore should be referred for evaluation of liver transplantation. While the initial management of uncomplicated ascites with low-sodium diet and diuretic treatment is straightforward in the majority of patients, there is a group of patients who fail to respond to diuretics and develop refractory ascites. The development of specific associated complications such as dilutional hyponatremia may further challenge the management of patients with ascites. New pharmacological agents such as the V2 receptor antagonists, drugs that directly antagonize the effects of elevated plasma antidiuretic hormone levels, induce solute-free water diuresis and seem to be promising in the management of patients with cirrhosis, ascites, and dilutional hyponatremia. This article focuses on the pathophysiology, clinical consequences, current management, and new treatment modalities for ascites and dilutional hyponatremia in cirrhosis.
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PMID:The management of ascites and hyponatremia in cirrhosis. 1829 76

The hepatorenal syndrome (HRS) is an acute functional renal failure due to renal arterial vasoconstriction occurring in cirrhotic patients with vascular dysfunction. The renal arterial vasoconstriction is the result of diffuse arteriole vasodilatation. There are two types of HRS, which can be differentiated according to the course and the stage of the renal failure; they have a different prognosis. Liver transplantation remains the standard treatment. Maintenance medical therapy is mainly based on vasopressin analogues. The interest of both dialysis and portosystemic intrahepatic shunt techniques remains to be determined. The prognosis of HRS is poor and in the absence of treatment, onset is usually followed by rapid fatal outcome.
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PMID:[Hepatorenal syndrome]. 1851 53

Hepatorenal syndrome is a form of acute or sub-acute renal failure which develops in patients with chronic liver disease. In contrast to other forms of acute renal failure it may be reversible using pharmacological agents. The pathogenesis involves splanchnic vasodilatation and intense renal vasoconstriction. Increasing intravascular volume and prolonged treatment with vasoconstrictor drugs reverses renal failure in a significant proportion of patients. Agents currently used include the vasopressin analogues terlipressin and the alpha1-adrenoceptor agonist midodrine. The somatostatin analogue octreotide has been used in combination therapy but is ineffective as monotherapy. Intravenous albumin is an important adjunctive treatment both in the prevention and treatment of hepatorenal syndrome. Increasing intravascular volume using TIPS (transjugular intrahepatic stent shunt) is effective in some patients and may be useful in maintaining patients who have initially responded to pharmacological therapy. Despite improvements in survival, long term prognosis is still poor and generally depends on the degree of reversibility of the underlying liver disease or access to liver transplantation.
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PMID:Management of hepatorenal syndrome. 1853 34


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