Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Active treatment has produced a dramatic decline in the 'mechanical' complications of hypertension (haemorrhagic stroke, congestive heart failure, renal failure, and aortic dissection) but has had no effect on the 'thrombotic' complications (thrombotic stroke, and myocardial infarction). There is a growing body of opinion that this failure is related to changes in the metabolism of lipoproteins and carbohydrates induced by anti-hypertensive drugs, which actively counteract the beneficial effects of a lowered blood pressure. The literature on this subject is extensive, but the results are inconclusive and much remains to be learned. In the light of present knowledge, it would appear to be prudent to choose anti-hypertensive drugs with care, concentrating upon proven agents which produce minimal biochemical disturbances, rather than using drugs which are known to have marked effects on lipoprotein metabolism.
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PMID:The metabolic effects of diuretics and other antihypertensive drugs: a perspective as of 1989. 197 68

Fenoldopam (SK&F 82526) is a short-acting selective dopamine-1 agonist in clinical trials for the treatment of hypertension, congestive heart failure and renal failure. In the present study, we tested various N-ethyl carbamate esters of fenoldopam in the conscious dog instrumented with a femoral arterial Vascular-Access-Port and a renal artery flow probe. Oral administration of SK&F R-82526 at 1 and 3 mumol/kg resulted in transient (30-60 min) dose-dependent increases in plasma fenoldopam levels and renal blood flow. Administration of the 7,8-bis-N-ethyl carbamate ester of R-fenoldopam (SK&F R-106114) and the 4',7,8-tris-N-ethyl carbamate ester of R-fenoldopam (SK&F R-105058) at 1, 3 and 10 mumol/kg p.o. also resulted in dose-dependent increases in plasma fenoldopam levels and renal blood flow; however, both parameters remained elevated for at least 4 hr. Intravenous administration of SK&F R-105058 also resulted in sustained plasma fenoldopam levels and increases in renal blood flow, indicating that slow absorption was not the cause of the sustained effect. The present study indicates that N-ethyl carbamate esters of fenoldopam are fenoldopam prodrugs which result in sustained increases in renal blood flow and plasma fenoldopam levels.
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PMID:Identification of fenoldopam prodrugs with prolonged renal vasodilator activity. 197 20

Despite the well characterized physiologic effects of aortocaval or iliac arteriovenous fistulas, patients with such uncommon lesions may manifest a diverse array of symptoms, and diagnosis is often delayed or overlooked. To examine clinical features that facilitate recognition and allow successful repair, a 30-year experience with 20 such fistulas was reviewed. Fourteen fistulas were caused by aneurysm erosion, four followed iatrogenic injury during lumbar disk surgery, and two developed from abdominal gunshot wounds. The interval from presumed occurrence to diagnosis ranged from 3 hours to 8 years. The diagnosis was not recognized before surgery in five (25%) patients. Back pain (70%) was the most common symptom. The presence of a typical abdominal bruit (80%) was the most reliable physical finding, but its significance was occasionally overlooked or misinterpreted. Congestive heart failure was prominent in only seven (35%) patients. Severe lower extremity edema and mottling was the primary manifestation in eight cases, often causing initial confusion with venous thrombosis. Hematuria (5 patients) and oliguric renal failure (4 patients), both fully reversible after fistula repair, also caused diagnostic uncertainty. The mean preoperative cardiac output was 12.2 L/min, falling to 5.4 L/min with fistula repair. Mean blood loss was 5960 ml, supporting use of intraoperative autotransfusion. Two operative deaths (10%) occurred, both in patients not correctly diagnosed before surgery. Despite varied modes of presentation, prompt recognition and use of appropriate operative techniques should achieve successful repair.
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PMID:Aortocaval and iliac arteriovenous fistulas: recognition and treatment. 199 Jan 67

Sonographic identification of thickening of the gallbladder wall that consists of multiple striations (alternate hypoechoic and hyperechoic layers) has been considered strong evidence of the presence of acute cholecystitis. We studied 27 patients in whom sonograms showed striated thickening of the gallbladder wall to determine the diagnostic significance of this finding. Striations were classified as focal or diffuse. Sonograms were correlated with pathologic findings in 16 patients and with clinical diagnoses and laboratory findings in 11. Patients were categorized as having cholecystitis with or without gangrene or edema of the gallbladder wall unrelated to gallbladder disease. Striated thickening of the gallbladder wall was due to cholecystitis in 10 patients, and all 10 had gangrenous changes at surgery or at pathologic examination. Striations were focal in eight of these patients and diffuse in two. Striated thickening of the gallbladder wall was due to edema of the wall unrelated to gallbladder disease in 17 patients. Causes included congestive heart failure (n = 4), renal failure (n = 5), liver disease (hepatic failure [n = 1], hepatitis [n = 6]), ascites (n = 2), hypoalbuminemia (n = 3), pancreatitis (n = 1), blockage of the lymphatic/venous drainage of the gallbladder (n = 2), and prominent Rokitansky-Aschoff sinuses (n = 1). More than one abnormality was present in five patients. Striations were focal in 11 of these patients and diffuse in six. The sonographic finding of striated gallbladder wall thickening is no more specific for cholecystitis than the observation of gallbladder wall thickening by itself, and it may occur in a variety of diseases. However, in the clinical setting of acute cholecystitis, the presence of striations suggests gangrenous changes in the gallbladder. The extent of the striations (focal or diffuse) is not useful in predicting the cause of the striated gallbladder wall thickening.
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PMID:Sonography of the gallbladder: significance of striated (layered) thickening of the gallbladder wall. 201 56

The use of antihypertensive drug treatment has altered the natural history of hypertension. Whereas congestive heart failure, cerebral hemorrhage, and renal failure were the major complications of untreated severe hypertension, myocardial infarction and thrombotic stroke have emerged as the major problems in treated hypertensives. None of the major therapeutic trials in hypertension have provided evidence that reducing blood pressure reduces the risk of atherosclerotic complications of hypertension. Hypertension certainly aggravates the severity of atheromatous lesions in experimental animals and, thus, may do so in humans. However, atherosclerosis is more closely related to disturbances in lipoprotein metabolism than to other factors. The common finding that serum cholesterol is raised in hypertensive patients may be due to atherosclerosis being the primary lesion, with the hypertension as a secondary complication rather than the primary lesion.
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PMID:Hypertension and vascular disease. 202 54

Diuretics are classified according to their site of action in the nephron: loop diuretics, thiazides, and antikaliuretics. During peak diuresis the pattern of electrolyte excretion is constant and characteristic for a class of diuretics. The ratio of diuretic-induced excretion of K+ to Na+ is 0.12 for loop diuretics, 0.20 for thiazides, and -0.21 for antikaliuretics. The ratio of Ca2+ to Na+ is 0.02 for loop diuretics and 0.003 for thiazides. Mg2+ excretion follows K+ excretion in a ratio of 0.15. The natriuretic effect of a diuretic directly depends on the renal clearance of the drug and is proportionate to the number of intact nephrons. Not only loop diuretics but also thiazides and antikaliuretics were demonstrated to be effective natriuretic drugs down to end-stage renal disease. In renal failure FENa is doubled with every halfening of GFR. Loop diuretics increase FENa to a maximum of 24%, thiazides to 10-15%, and FENa is doubled by antikaliuretics. Comedication of loop diuretics with thiazides in renal failure may therefore be more effective than increasing monotherapy. In liver disease, nonrenal drug clearance is reduced the more the patient's direct bilirubin rises thus causing an increase in AUC and urinary excretion of parent drug and metabolites. Despite increased Ae, the cirrhotic patient may become resistant to diuretics as many patients with congestive heart failure or nephrotic syndrome. This is considered to be due to reduced Na+ load available at the diuretic's site of action following avid proximal Na+ reabsorption. In reduced EABV a short-term comedication of loop diuretics with carboanhydratase inhibitors is considered a more effective diuretic strategy than vigorously increasing monotherapy.
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PMID:Pharmacodynamic and kinetic considerations on diuretics as a basis for differential therapy. 203 73

The clinical features of eight patients, four females, aged 4 to 15 years under chronic hemodialysis for terminal renal failure (creatinine clearance 10 ml.min.1,73 m2 or less) are reported. Initial diseases were Alport syndrome, systemic lupus erythematosus, chronic glomerulonephritis (n = 2), bilateral polycystic kidney, prune belly syndrome and reflux nephropathy (n = 2). Distal vascular approach by means of arteriovenous fistulas was preferred for these patients and the kinetic urea model was used to evaluate the performance of the procedure. Patients required nine to twelve hours of hemodialysis per week for optimal results. Mean weight decreases of 1 to 3 kg and reductions in blood urea nitrogen and serum potassium of 40 mg.dl and 2,5 mEq.1, respectively, were observed. The main complications of hemodialysis were the disequilibrium syndrome, infections at the site of insertion of the arteriovenous fistulae and congestive heart failure. Three patients were submitted to renal transplantation with live donors homografts: one died and the other two remain alive but under chronic hemodialysis. Five children are attending school regularly, and two of them are waiting a kidney donor for transplantation. Despite encouraging results chronic hemodialysis in children constitutes only primary supportive therapy prior to renal transplantation.
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PMID:[Chronic hemodialysis in children]. 208 91

The heart atrium, as well as under certain pathophysiological conditions the ventricle, synthesize and release ANP. Exerting natriuretic, diuretic and vasorelaxant effects, this peptide plays an important role in the body's blood volume and blood pressure homeostasis. Whereas the pharmacological actions of ANP have been quite convincingly demonstrated, its physiological and pathophysiological role is less well defined. ANP plasma levels tend to be increased in diseases with salt and water retention, such as essential hypertension, congestive heart failure, renal failure or liver cirrhosis. With regard to its hemodynamic effects, ANP seems to be beneficial in patients with hypertension. ANP appears to have little therapeutic potential as a diuretic in patients with congestive heart failure and liver cirrhosis, possibly due to the decreased renal responsiveness to ANP in these diseases. However, ANP might to be a valuable therapeutic agent in acute renal failure.
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PMID:[Atrial natriuretic peptide. II. Pathophysiology and possible clinical significance. Review]. 214 57

The discovery of atrial natriuretic peptide (ANP) has modified our current understanding of the regulation of sodium metabolism. This peptide, of which the second messenger is cyclic guanosine monophosphate (cyclic GMP), is released by the atrial myocytes in response to increased atrial stretch and has for essential function to diminish the venous return to the heart. Radioimmunoassays have demonstrated that plasma ANP and cyclic GMP levels are increased in various diseases such as congestive heart failure (CHF), renal insufficiency, and, to a lesser extent, diabetes mellitus and liver cirrhosis with ascites. Plasma ANP is of prognostic value in CHF and reflects the effective central volemia in renal failure so that its assay as well as that of plasma cyclic GMP seem of interest in these diseases. Further studies are needed to assess the pathophysiological significance of ANP in diabetes mellitus and cirrhosis, and to define the indications of the treatment by enkephalinase inhibitors which increase endogenous ANP levels by lowering the catabolism of this hormone.
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PMID:Current indications of plasma atrial natriuretic peptide measurements in human diseases. 215 73

Thirty-seven patients with volume-retaining disorders (liver cirrhosis with ascites, n = 8; heart failure NYHA III-IV, n = 12; endstage renal failure, n = 17) and twelve healthy age-matched controls were given a small dose (33 micrograms) of hANF (human atrial natriuretic factor). We tested the resulting hemodynamic and renal effects as well as the effect on plasma cyclic GMP levels and compared them with the properties of platelet ANF receptors. The ANF injection evoked an increase in cyclic GMP plasma levels of 19.3 +/- 2.2 nM in healthy controls. This increase tended to be smaller in the cirrhosis group (15.5 +/- 3.3 nM) and in the heart failure group (16.8 +/- 2.3 nM) than in the dialysis group (20.5 +/- 2.5 nM). The invasion rates of cyclic GMP were comparable in all groups, but the evasion rates increased more in the heart failure and endstage renal failure groups (27.9 +/- 7.7 min and 26.1 +/- 3.4 min, respectively) than in the cirrhosis and control groups (14.9 +/- 1.9 min and 14.2 +/- 1.9 min, respectively). Patients with endstage renal failure and congestive heart failure showed a smaller decrease in diastolic blood pressure than controls and patients with liver cirrhosis. Renal actions of ANF were diminished in cirrhosis and heart failure patients. Binding capacities of platelet ANF receptors were higher in the control group (12.2 +/- 1.5 receptors/cell) than in the patient groups (cirrhosis, 7.8 +/- 1.2; endstage renal failure, 8.0 +/- 0.9; heart insufficiency, 8.0 +/- 1.0 receptors/cell), with no differences among the patient groups. Binding affinities were not significantly different. Correlation analysis showed that the relationship between the actions of ANF and the increases in plasma cyclic GMP levels is loose and cannot predict the hemodynamic or renal effects of exogenous ANF in a given patient. Although the behavior of plasma cyclic GMP levels fails to predict the responsiveness of the body to ANF in a given patient, it does reflect the differences between the patient groups and the control group. In contrast, we found no correlation between the properties of platelet ANF receptors and ANF action.
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PMID:Effects of a small bolus dose of ANF in healthy volunteers and in patients with volume retaining disorders. 216 5


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