Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve patients with cirrhosis, refractory ascites, and varying degrees of renal failure (creatinine clearance, 5 to 44 ml/min) were studied before and up to 2 weeks following peritoneovenous shunt. Creatinine clearance increased 60% or more in seven patients (group I) and 22% or less in five patients (group II). There were no significant differences in maximum urine output or sodium excretion between groups (group I, 4,272 ml/14 hr, 372 mEq/24 hr; group II, 3,722 ml/24 hr, 255 mEq/24 hr). Aldosterone and renin concentrations were higher in group I and showed a greater decrease after shunting. Renin substrate levels also were higher in group I and rose following shunt insertion, while group II remained low. Ascitic fluid was found to contain renin substrate in concentrations of approximately 25% to 50% of plasma concentrations. Patients with the greatest increase in creatinine clearance showed the largest rise in substrate concentration and fall in renin and aldosterone secretion, suggesting a dynamic relationship between these factors. That a diuresis could occur without significant change in these parameters in five of 12 patients suggests independent control mechanisms for renal salt and water excretion and glomerular filtration in the ascitic patient.
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PMID:Improved renal function and inhibition of renin and aldosterone secretion following peritoneovenous (LeVeen) shunt. 66 20

The work was designed to study the effects of a meat meal on glomerular filtration rate (GFR), renal plasma flow (RPF), and plasma concentrations of glucagon, insulin, growth hormone, renin, aldosterone, total amino acids, and NH3 in healthy humans (H) as well as in patients with Child A liver cirrhosis (LC). The meat meal produced renal hyperaemia and hyperfiltration without changes in the filtration fraction. Fractional Na excretion in urine increased significantly after the meat meal only in LC. Hyperinsulinaemia and hyperglucagonaemia were seen at baseline in LC and were not affected by the meat meal, whereas in H glucagon concentration increased significantly over baseline within 30 min from the meat meal and insulin within 60 min. Growth hormone concentration was normal at baseline in LC and increased significantly 120-180 min after the meal, whereas it was not affected in H. Renin and aldosterone were stable in both H and LC. Plasma amino acid concentration began to increase 60 min after the meat meal, when hyperfiltration was present. The data indicate that in human Child A cirrhosis of the liver renal haemodynamic response to a meat meal is independent of changes in glucagon.
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PMID:Glucagon-independent renal hyperaemia and hyperfiltration after an oral protein load in Child A liver cirrhosis. 155 40

Plasma renin activity, angiotensinogen, active renin and aldosterone concentrations and, 1 hour after addition of trypsin 1 mg per ml of plasma at -4 degrees C, prorenin and total renin concentrations were measured in 49 normotensive volunteers. Renin activity and active renin concentration were correlated (n = 98, r = 0.902, p less than 0.01) and their ratio was not dependent on the angiotensinogen concentration. Prorenin accounted for 90 per cent of total renin and was 40 per cent higher in males than in females in both supine and upright positions (p = 0.02 and p = 0.01). The change in position markedly increased plasma renin activity as well as active renin and aldosterone concentrations and, to a lesser degree, prorenin concentration, thereby raising the active/total renin ratio. Plasma renin activity, active renin concentration and plasma aldosterone concentration were significantly and negatively correlated with age, but not with urinary sodium excretion. Plasma renin activity and active renin and angiotensinogen concentrations were also measured in 14 patients with high angiotensinogen concentration (pregnant women and oestrogen users) and in 14 patients with cirrhosis and subnormal angiotensinogen concentration. In these patients the ratio of plasma renin activity to active renin concentration was correlated with the angiotensinogen concentration (n = 28, r = 0.643, p less than 0.01). The slope of the regression line between renin activity and active renin concentration was significantly different in patients with cirrhosis and in healthy volunteers, the measurement of renin activity leading to a ten-fold underestimation of active renin concentration. In clinical investigations of the renin system, plasma samples should be handled at room temperature to avoid cryoactivation of prorenin. The determination of active renin concentration should be preferred to that of plasma renin activity because it is not influenced by physiological or pathological variations in angiotensinogen.
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PMID:[Recent advances in the clinical study of the renin system. Reference values and conditions of validity]. 252 79

The interrelationship between renal hemodynamics and the renin-angiotensin-aldosterone system in 28 nonazotemic cirrhotic patients has been studied. Patients were divided into three groups: A) Patients without ascites nor edema; B) Patients with ascites and a relatively high sodium excretion (41.9 +/- 12.9 mmol/day); and C) Patients with ascites and very low sodium excretion (4.8 +/- 0.6 mmol/day). Renin and aldosterone levels significantly increased in group C. A significant correlation was observed between plasma aldosterone concentration and urinary sodium excretion, and between plasma renin activity and aldosterone levels. There were no significant differences in urine flow, glomerular filtration rate, effective renal plasma flow, or renal blood flow between the three groups of patients, in spite of marked differences in renin and aldosterone levels. Renal perfusion was not related to plasma renin activity either in the overall sample of patients or in the individual groups. These results show that factors other than total renal perfusion are involved in renin secretion in cirrhosis.
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PMID:Renal hemodynamics and the renin-angiotensin system in cirrhosis. 270 70

We evaluated the dynamic response of renin, aldosterone, and vasopressin to intravenous water loading (20 ml 5% glucose/kg b.w.) in 12 children (aged 7-18 years) with postinflammatory liver cirrhosis after hepatitis B virus (HBV) infection. All of the patients had early-stage liver cirrhosis; according to Child's classification, nine patients had group A; three, group B cirrhosis. A group of 17 children with chronic persistent hepatitis served as the control. The diagnoses were confirmed in all of the patients by liver biopsy. The patients followed a diet containing 3 mmol NaCl/kg/day, maximum 100 mmol per day for 6 days. Water loading was performed in recumbency over approximately 45 min. Renin, aldosterone, and vasopressin, assayed by radioimmunoassay (RIA), were determined before, 1 h, and 5 h after starting the water load. Prestudy hormone levels were within normal range in both groups. Renin and aldosterone concentration change patterns were similar in both groups and characterized by suppression of hormone activity caused by central volume expansion and recovery to prestudy levels after 5 h. However, the pattern of change of vasopressin concentrations differed in the control and study groups. In contrast to that of the controls, volume expansion did not suppress vasopressin in the group with liver cirrhosis. We conclude that failure to suppress vasopressin activity after central volume expansion may be one of the early mechanisms responsible for water-electrolyte imbalance in liver cirrhosis in children.
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PMID:The renin-angiotensin-aldosterone system and vasopressin in early-stage liver cirrhosis after HBV infection in children. 787 98

Serum concentrations of ANF, Renin and Aldosterone were measured in animals with experimental cirrhosis and volume overload. We studied 75 Wistar rats divided in five groups. Group I: rats with hepatic cirrhosis induced by CCl4; Group II: Control rats; Group III: rats with hepatic cirrhosis and continuous infusion of saline serum; Group IV: control rats with continuous infusion and Group V: cirrhotic rats and bolus infusion of saline. There were no statistical differences in serum concentrations of ANF (232 +/- 75 vs 195 +/- 42 pg/ml) and Renin concentration (182 +/- 24 vs 171 +/- 34 ng/ml/hour) between controls and rats with cirrhosis. However, Aldosterone levels were elevated in cirrhotic rats in basal conditions as compared to controls (1197 +/- 287 vs 475 +/- 88 pg/ml; p < 0.001). The volume overload caused a paradoxical decrease of ANF in cirrhotic rats (124 +/- 15 and 122 +/- 17; p < 0.001). On the other hand, no changes were observed in Renin and Aldosterone after volume expansion. These results suggest the existence of a hemodynamic response to compensate the volume overload. Other studies are necessary to confirm this hypothesis.
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PMID:[Effects of blood volume expansion on atrial natriuretic factor and the renin-aldosterone axis in experimental cirrhosis]. 803 15

Renin-angiotensin system plays a prominent role in the sodium and water homeostasis. In addition, activation of renin-angiotensin system frequently occurs in patients with cirrhosis and ascites. Theoretically, administering of angiotensin converting enzyme inhibitors can enhance sodium and water retention in cirrhotic patients with ascites. In this study, we evaluate the role of low-dose captopril on renal function changes, renal plasma flow and hemodynamics in patients with cirrhosis and ascites. Fifty patients are randomly assigned to receive captopril or placebo for 14 days. Renal functions, renal plasma flow, plasma renin activity, plasma aldosterone concentration and systemic and hepatic hemodynamics are measured before and after treatment. Our results indicate that placebo administration did not affect any of the parameter measured in this study. The finding that low-dose captopril significantly increases plasma renin activity suggests that the dose used in this study effectively blocks the enzyme activity. However, low-dose captopril does not affect renal plasma flow, renal functions and systemic and hepatic hemodynamics. Results in this study demonstrate that inhibition of angiotensin converting enzyme alone may not improve sodium and water retention in cirrhotic patients with ascites.
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PMID:Effects of captopril on renal functions, renal and portal hemodynamics in patients with cirrhosis. 893 43

Spironolactone, a competitive aldosterone receptor antagonist (ARA), has traditionally been the treatment of first choice in idiopathic hyperaldosteronism (IHA) and for preoperative management of aldosterone producing adenoma (APA). Spironolactone is partially absorbed, is extensively metabolized mainly by the liver and its therapeutic properties are attributable to active metabolite canrenone. At therapeutic doses of 25 to 400 mg per day, spironolactone effectively controls blood pressure and hypokalemia in the majority of cases. Endocrine side effect are often associated and mainly consist of gynecomastia, decreased libido and impotence in man and menstrual irregularities in women. Canrenone and the K+ salt of canrenoate are also in clinical use: they avoid the formation of intermediate products with anti-androgenic and progestational actions, resulting in a decreased incidence of side effects. Furthermore, a relatively new selective ARA compound (eplerenone) with reduced affinity for androgen and progesterone receptors, is currently undergoing clinical trials. In essential hypertension aldosterone can contribute to hypertension and increases the incidence of myocardial hypertrophy and cardiovascular events. On the other hand, inhibition of Renin-Angiotensin-Aldosterone System (RAAS) is associated with a decrease in blood pressure, with a regression of left ventricular hypertrophy and a reduction of target organ damage. Thus, ARA have been proposed as complementary treatment associated to ACE inhibitors and angiotensin receptor antagonists. Aldosterone is also known to play an important role in pathophysiolgy of congestive heart failure (CHF). In vitro and in vivo evidences suggest that aldosterone promotes myocardial fibrosis. This effect reflects direct, extra-epithelial actions of aldosterone via cardiac MR which are counteracted by ARAs in animal models. The RAAS is chronically activated in CHF. Non potassium-sparing diuretics further stimulate the RAAS and cause hypokalemia. Thus, use of ARAs in CHF was first proposed to correct potassium and magnesium depletion. At present ARAs are indicated in the management of primary hyperaldosteronism, in oedematous conditions in patients with CHF, in cirrhosis of the liver accompanied by oedema and ascites, in essential hypertension and in hypokalemic states. Its indication as adjunctive therapy of heart failure is currently under investigation. In fact, it is well known that even high doses of ACE inhibitors may not completely suppress the RAAS; aldosterone 'escape' may occur through non angiotensin II dependent mechanisms. Addition of spironolactone to an ACE inhibitor causes marked diuresis and symptomatic improvement. During the last few years, the RALES study (Randomized Aldactone Evaluation Study) was organized to explore the efficacy of combination therapy with spironolactone and ACE inhibitor in patients with CHF, class III or IV NYHA. The study was stopped 18 months early because the results were so statistically and clinically significant that it would be unethical to continue the trial. It is reported a 30 percent decrease in mortality and hospitalisation for cardiac causes in spironolactone-treated group vs placebo group.
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PMID:Aldosterone antagonists in hypertension and heart failure. 1079 May 93

Tense ascites is one of the most disabling and distressing manifestation of liver cirrhosis. In the presence of ascites alteration in ventricular function is marked. Renin-angiotensin-aldosterone and sympathetic nervous system, whose activation is marked when tense ascites develops, could be involved as pathogenic factors causing increased left ventricular wall thickness. Large volume paracentesis (LVP) is an old but safe and effective procedure to mobilize ascitic fluid in cirrhotic patients. The study evaluated the left ventricular function in patients with liver cirrhosis and tense ascites and determine the effect of total abdominal paracentesis on cardiac performance and correlated between cardiac performance and some humoral factors (renin, aldosterone, nor-epinephrine and epinephrine) in cirrhotic patients with ascites. Fifty cirrhotic patients with tense ascites, besides 20 normal persons matched with patients in age and gender as a control group were included in our study. All patients were hospitalized and, submitted to a 4 days bed rest, low sodium diet and subjected to full investigations clinically and laboratory. Abdominal paracentesis was done to all patients (mean volume 7.5 + 11.7 L) with dexran-70 infusion. Blood samples were taken before and immediately after paracentesis for neurohormonal assay (plasma rennin activity PRA, plasma aldosterone PA, plasma nor-epinephrine and epinephrine). The plasma renin activity, plasma aldosterone, plasma epinephrine, and plasma nor epinephrine was significantly higher than control. They showed significant reduction after paracentesis but still significantly higher than control levels. The results showed that sudden abdominal decompression could play a role in the post paracentesis systemic haemodynamic changes through mechanical decompression of the splanchinic vascular bed. Total paracentesis with albumin infusion causes immediate favorable effects; increasing cardiac output, suppressing plasma renin activity and plasma aldosterone, decreasing serum createnine and blood urea nitrogen and reducing portal pressure and Porto collateral blood flow.
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PMID:Large volume abdominal paracentesis effect on some humoral factors and cardiac performance in patients with liver cirrhosis and tense ascities. 1798 89

Angiotensin converting enzyme (ACE) is a key player of Renin Angiotensin System (RAS), involved in conversion of active product, angiotensin-II. Alterations in RAS have been implicated in the pathophysiology of various diseases involving heart, kidney, lung and liver. This study is designed to investigate the association of ACE gene expression in induction of liver cirrhosis in rats. Total 12 male albino Wistar rats were selected and divided in two groups. Control group received 0.9% NaCl, where as Test group received thioacidamide (TAA), dissolved in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight, twice a week for 12 weeks. The rats were decapitated and blood sample was collected at the end of experimental period and used for liver functions, enzyme activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was isolated from excised tissue determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RT-PCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels were significantly high (p<0.05) and level of MDA was significantly low (p<0.05) in TAA treated rats as compared to control rats. The ACE gene expression after 12 weeks TAA treatment in cirrhotic rats was significantly increased (p<0.05) in comparison to controls. This study describes the importance of RAS in the development of hepatic fibrosis and the benefits of modulation of this system ACE gene expression. The finding of major up-regulation of ACE in the experimental rat liver provides further insight into the complexities of the RAS and its regulation in liver injury. The development of specific modulators of ACE activity and function, in future, will help determine the role of ACE and its genetic variants in the pathophysiology of liver disease.
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PMID:Angiotensin converting enzyme (ACE) gene expression in experimentally induced liver cirrhosis in rats. 2403 38


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