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)

Recent studies have suggested a role for thromboxane in the progression of renal disease. The current study evaluated the role of this arachidonic acid metabolite in a model of renal disease which bears many biologic similarities to that in the kidneys of patients with chronic progressive renal failure. The model is that induced by ferritin-anti-ferritin immune complex nephritis in Dahl-salt sensitive rats rendered hypertensive by a high salt intake. Rats with this model of renal disease were chronically given a thromboxane synthetase antagonist OKY-046 or a placebo treatment from 16 to 29 weeks of age. Sequential observations of serum creatinine and 24-hour urinary protein excretion showed an ameliorating effect of OKY-046 on these renal parameters. Histologic examination of the kidneys also showed significantly less glomerular sclerosis in OKY-046 treated animals. The efficacy of OKY-046 was monitored by measurements of serum TXB2 levels and of glomerular production of TXB2 (and other prostaglandins); amounts of TXB2 were significantly reduced in the OKY-046 group. It is concluded that blockade of thromboxane generation has been successful in ameliorating the functional and structural lesions in this model of renal disease, providing further support to the thesis that thromboxane is an important mediator in events leading to eventual chronic renal failure and sclerosis.
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PMID:A thromboxane synthetase antagonist ameliorates progressive renal disease of Dahl-S rats. 296 73

The catalytic activities of Na+-K+-ATPase and succinate dehydrogenase, marker enzymes for active salt reabsorptive capacity of renal basolateral plasma membranes and for respiratory capacity of mitochondrial cristae membranes, were studied in the maintenance phase of human acute post-transplant renal failure. Biopsies of 4 kidney-allografts taken at transplantation operation and additionally at different post-transplantation periods, either with good function or in various stages of dysfunction, were compared with the unaffected part of a human kidney nephrectomized due to hypernephroma. In single nephron segments, Na+-K+-ATPase activity was determined after microdissection by microfluorometry, and succinate dehydrogenase activity was determined by a microphotometric procedure in stained cryosections. In intraoperative and postoperative biopsies of a well-functioning allograft, both Na+-K+-ATPase and succinate dehydrogenase activities did not differ from those of normal renal tissue. In contrast, the catalytic activities were found to be decreased in the distal tubules of 2 anuric allografts when compared with their intraoperative controls. In addition, succinate dehydrogenase activity was reduced in distal tubules of a recovering allograft. Catalytic activities appeared to be unaffected in glomeruli, proximal tubules, and collecting ducts. It is suggested that the predominant distal tubular alterations with regard to these parameters are a consequence of increased distal tubular vulnerability due to circulatory and metabolic conditions.
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PMID:Altered distribution pattern of Na+-K+-ATPase and succinate dehydrogenase activities along the nephron in human acute post-transplant renal failure. 298 8

CHF may activate the RAS by various mechanisms. Acute CHF is associated with high PRA, whereas chronic, stable disease is combined with normal values. The response to ACEI is affected by blood pressure, degree of activation of the RAS, salt balance and degree of possible renal failure. It may also be affected by concomitant diuretic or, e.g., digoxin therapy. ACEI improves RPF, GFR may remain normal or may increase, if it was previously impaired due to reduced RPF. Severe hypotension in combination with decreased autoregulatory capacity may decrease GFR. Generally, renal excretion of sodium and water increase. These changes in renal handling of salt and water are primarily caused by decreased AII. They are also augmented by inhibited sympathetic tone and thirst and decreased release of ADH and aldosterone. Increased synthesis of vasodilating and natriuretic PGs is probably also of some importance. Dilutional hyponatremia may be corrected by combined ACE inhibitor and furosemide treatment. Water and sodium excretion increase and sodium is redistributed from the intracellular space. Low serum sodium values increase and azotemia may be corrected, if ACE inhibitor doses are carefully titrated to avoid severe hypotension. These effects are ascribed mainly to a decrease of AII, thirst and ADH release. The effect of furosemide is improved since increased amounts of salt are delivered to the loop of Henle and access of furosemide to its site of action is facilitated by increased RPF. ACEI does not cause any obvious negative effects on renal handling of salt and water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ACE inhibition on renal regulation of salt and water. 301 59

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.
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PMID:Bile salts as endogenous digitalis like factors. 301 98

There is increasing evidence for endogenous, circulating compounds that interact with the digitalis receptor of [Na,K]ATPase and with antidigoxin antisera. Circulating levels of these digitalis-like compounds increase in response to fluid or salt loading and appear to play a role in diseases characterized by fluid and salt retention, e.g. renal failure, liver disease, acromegaly, experimental and human hypertension, and preeclampsia. Because of assay nonspecificity, many diverse substances are being measured. Of the few compounds currently identified as having "digitalis-like" activity, none appears to be the natural ligand of the digitalis receptor and none appears linked with hypertension. Nevertheless, research still suggests that digitalis-like factors may have a central role in essential hypertension and related disorders.
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PMID:Endogenous digitalis-like natriuretic factors. 303 37

With the failure of the heart as a pump, there ensues a series of neurohumoral compensations that defend organ perfusion at the expense of alterations in cardiac filling pressures and the distribution of blood flow to various regional circulations. Activation of the sympathetic nervous system and the renin-angiotensin II-aldosterone system and increases in circulating arginine vasopressin maintain arterial blood pressure by producing systemic arteriolar vasoconstriction and the renal retention of salt and water. Constriction of the efferent arterioles in the kidney by angiotensin II and norepinephrine promotes reabsorption of glomerular filtrate in the peritubular capillaries and maintains glomerular filtration in the face of declines in glomerular plasma flow and the glomerular permeability-surface area ultrafiltration coefficient. In resting, sodium-replete, conscious animals and humans, pharmacologic inhibition of renal cyclo-oxygenase by nonsteroidal anti-inflammatory drugs has little or no effect on renal hemodynamics. However, electrical or reflex stimulation of the renal nerves, intrarenal infusion of angiotensin II, or infusion of arginine vasopressin stimulates the release of vasodilator prostaglandins from the kidneys. In sodium-depleted animals or humans, and when cardiac output decreases, there is an increase in total peripheral vascular resistance but little change in renal vascular resistance. Increased renal synthesis of vasodilator prostaglandins (presumably by the blood vessels) maintains renal blood flow despite increased release of renin and norepinephrine from the kidneys. In these situations, pharmacologic inhibition of renal cyclo-oxygenase is accompanied by marked reductions in renal blood flow and glomerular filtration rate. When this occurs in patients with advanced heart failure, reversible oliguric renal failure may result. In this setting, cyclo-oxygenase inhibition may also increase arterial pressure and induce additional depression of cardiac function. Recent data indicate that blood vessels have the capacity to synthesize the sulfidopeptide leukotrienes C4, D4, and E4, which can constrict peripheral and renal blood vessels and alter vascular permeability. The vascular cell types responsible for leukotriene C4 synthesis and the potential roles of these vasoactive eicosanoids in kidney and other regional circulations are currently under study.
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PMID:Prostaglandins in congestive heart failure and the effects of nonsteroidal anti-inflammatory drugs. 309 62

Atherosclerosis and hypertension are, by far, the most common cardiovascular diseases affecting women, and both are influenced by diet. Atherosclerosis occurs more commonly in men than women; generally women are 10 to 15 years older than men when symptoms develop. The prevalence of hypertension is about equal in the two sexes, particularly in middle aged and older persons. These cardiovascular diseases are major causes of death and disability in this country. Atherosclerosis results in myocardial infarction, thrombotic strokes, and claudication. Hypertension, when severe, damages small blood vessels, causing kidney failure, hemorrhage, strokes, and heart failure; when the condition is mild to moderate, it produces atherosclerosis. Nutritional factors are of primary importance in both atherosclerosis and hypertension. Risk factors for atherosclerosis related to nutrition are hypercholesterolemia, hyperglycemia-diabetes, and for hypertension, obesity, high salt intake, and excessive use of alcohol. Of all these risk factors, obesity seems to be the most important because it is strongly linked to hypertension and diabetes. Dietary intake of saturated fat is a potent factor in determining the blood cholesterol level, and reducing intake often decreases the level, thus lessening the risk of atherosclerotic complications. Although high salt intake and excessive alcohol use produce hypertension in susceptible people, less is known about the frequency of this adverse effect than is known about obesity.
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PMID:Nutrition and cardiovascular diseases of women. 312 Feb 15

The relative importance of salt intake and psychosocial stimulation in the development of high blood pressure has been studied in colonies of CBA/USC mice. Approximately 50 males were observed for 3-4 months in five population cages which successfully induced chronic psychosocial interaction, resulting in chronic hypertension. Under these conditions, progressive arteriosclerosis develops together with myocardial hypertrophy, increased catecholamine synthesis and increased angiotensin sensitivity. Previous work indicates that this condition shows the characteristics of renin dependent human hypertension. A special grain based diet was used which included 0.014% sodium. This resulted in the ingestion of the equivalent of 40 mmol/l sodium or 3.0 g NaCl in a 70-kg man. This, and an even more stringent synthetic diet containing less than 0.01% NaCl, i.e. less than 2 g NaCl per day in man, were contrasted with the standard chow which contains 0.4% sodium. Over 4 months of social interaction the psychosocial stimulation proved to be the critical factor and, despite the low-salt intake, blood pressure rose to the same levels as those of control groups on a normal diet containing 1% salt. Hypertension occurs in the absence of kidney failure as assessed by blood urea. Plasma renin levels on the low-salt grain based diet were double those on standard chow, showing that the diet was sufficiently low in salt to activate the renin-angiotensin system.
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PMID:Psychosocial stress induces high blood pressure in a population of mammals on a low-salt diet. 328 Jun 77

A case of long-term acetaminophen overdosage in a six-year-old child, which contributed to her death despite optimal medical management including oral acetylcysteine therapy, is reported. Acetaminophen 325 mg every six hours was prescribed for fever associated with measles. Believing that acetaminophen was nontoxic, the child's mother progressively increased the dose over three days, first in response to fever and subsequently for abdominal pain probably secondary to unrecognized acetaminophen toxicity. On admission to the hospital, the patient's serum acetaminophen concentration was 163 micrograms/mL (11 hours after the last dose); subsequently, the acetaminophen half-life was determined to be 15 hours. A course of oral acetylcysteine therapy (a loading dose of 140 mg/kg as the sodium salt followed by 70 mg/kg every four hours for 17 doses) was begun. Hepatic and renal failure developed within two days, followed by the onset of seizures, and brain death occurred on the 11th day. Autopsy findings consistent with acetaminophen toxicity included centrilobular hepatic and renal tubular necrosis. Aspergillis fumigatus and Cryptococcus neoformans isolates from pulmonary abscesses and bronchopulmonary lymph nodes, respectively, were an unexpected finding. However, in the absence of acetaminophen overdosage, death would have been unlikely. Cryptococcal lymphadenitis was believed to have been the initial febrile illness that was treated with supratherapeutic doses of acetaminophen. Fatalities in children from a single overdose of acetaminophen have been rare, and there is only one previous report of a fatality after long-term administration of multiple excessive doses. The lethal outcome in this case illustrates the need to educate the public on the potential toxicity of nonprescription medications.
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PMID:Death of a child associated with multiple overdoses of acetaminophen. 338 45

Non-steroidal anti-inflammatory drugs (NSAIDs) may produce acute renal failure, papillary necrosis and interstitial nephritis. These adverse drug reactions are rare but have been reported in patients with congestive heart failure, cirrhosis, renal parenchymal disease, lupus nephritis and hypertension. All these conditions may be associated with hypovolaemia and an activated renin-angiotensin system, when renal blood flow and glomerular filtration depend on local renal prostaglandin biosynthesis. A severe impairment of renal function may occur when this synthesis is inhibited by NSAID treatment. It is possible that 1 in 100 of elderly patients have renal parenchymal disease, 1 in 100 arteriolar nephrosclerosis, 1 in 200 unilateral or bilateral renal artery stenosis and an unknown number suffer from atheroembolic renal disease. Fortunately, only a small proportion of 'at risk' patients given NSAIDs appear to develop renal failure. Perhaps bilateral renal disease or salt depletion are necessary factors? Whatever the explanation, NSAIDs should be used with caution in the elderly.
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PMID:Pharmaco-epidemiological considerations in patients with arthritis and vascular disease of the kidney. 349 36


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