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)

Ischemic renal disease (IRD) is defined as a clinically important reduction in glomerular filtration rate or loss of renal parenchyma caused by hemodynamically significant renal artery stenosis. IRD is a common and often overlooked clinical entity that presents itself in the setting of extrarenal arteriosclerotic vascular disease in older individuals with azotemia. Eleven to 14% of end-stage renal disease (ESRD) cases are attributable to chronic IRD. A high percentage of patients entering ESRD programs are hypertensive. Many patients with a presumed diagnosis of hypertensive nephrosclerosis actually have undiagnosed ischemic nephropathy as the etiology of their ESRD. It is important for the clinician to identify IRD, because IRD is a potentially reversible cause of chronic renal failure in a hypertensive patient. Atherosclerotic renal artery disease is common among patients with coronary artery disease and aortic and peripheral vascular disease. Atherosclerotic renal artery disease is a progressive disorder, and its progression is associated with loss of renal mass and functioning. A decrease in glomerular filtration rate sufficient to cause an elevation of the serum creatinine concentration requires injury to both kidneys. Consequently, IRD can arise from one of two main clinical situations: bilateral hemodynamically significant renal artery stenosis leading to bilateral renal ischemia; and hemodynamically significant renal artery stenosis in a solitary functioning kidney, or in a kidney that is providing the majority of a patient's glomerular filtration. The primary reason for establishing the diagnosis of IRD is the hope that correction of a renal artery stenosis will lead to improvement of renal function, or a delay in progression to ESRD. There are six major clinical settings in which the clinician could suspect IRD: acute renal failure caused by the treatment of hypertension, especially with angiotensin converting enzyme inhibitors; progressive azotemia in a patient with known renovascular hypertension; acute pulmonary edema superimposed upon poorly controlled hypertension and renal failure; progressive azotemia in an elderly patient with refractory or severe hypertension; progressive azotemia in an elderly patient with evidence of atherosclerotic disease; and unexplained progressive azotemia in an elderly patient. Noninvasive testing modalities that have been used recently include the angiotensin converting enzyme inhibitor renal scan, duplex Doppler sonography, magnetic resonance angiography, and the spiral computed tomography. Treatment methods include percutaneous transluminal angioplasty, endovascular stenting, and surgical revascularization. The results of treatment for preservation of renal function have been encouraging, with stabilization or improvement in renal function observed in a significant proportion of cases.
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PMID:Ischemic renal disease: an emerging cause of chronic renal failure and end-stage renal disease. 943 40

Oxidant injury is considered to be an important mechanism in the pathophysiology of acute renal failure. It has been thought that decrease in extracellular and intracellular fluid and endotoxemia seen in obstructive jaundice may cause an increase in production of oxygen free radicals and impairment in antioxidant defense mechanism. This study is designed to investigate the possible role of oxidant injury in renal failure seen in jaundiced patients. In this study, 28 rats were divided into four groups: Control (C)(N = 7); Renal ischemia (RI)(N = 7); Obstructive jaundice+renal ischemia (OJ+RI)(N = 7); Obstructive jaundice (OJ)(N = 7). All groups were compared with each other according to renal failure findings and enzyme activities, such as Xanthine oxidase (XOD), Superoxide Dismutase (SOD) and Catalase in renal cortex and Glutathione Peroxidase (GSH-Px), in blood at 3rd day after ischemia and reperfusion. Renal failure findings monitored by blood urea and creatinine levels, seemed more evident in OJ+RI than RI group (p < 0.05). When compared with RI, in OJ+RI group, increase in XOD activity at 3rd day was statistically significant [0.259 +/- 0.01 U/g (tissue) and 0.362 +/- 0.03 U/g (tissue) respectively] (p < 0.05). SOD and GSH-Px activities of each ischemic group at 3rd day were decreased compared to non-ischemic groups. This fall was significant (p < 0.05). But there was no statistical difference between jaundiced and non-jaundiced groups. Alterations in catalase activities also had no statistical significance. These findings may suggest that the injury induced by oxygen free radicals at re-oxygenation of tissue after ischemia may also play a role in the pathogenesis of acute renal failure developed in obstructive jaundice.
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PMID:The role of oxygen free radicals in acute renal failure complicating obstructive jaundice: an experimental study. 951 37

Vascular nephropathies are a steadily increasing cause of end-stage renal failure. Arterionephrosclerosis and arteriolonephrosclerosis are common features in the hypertensive patient. This is especially true for blacks of African descent, in whom hypertension and nephrovasculopathies are a major cause of renal insufficiency. That primary hypertension leads to renal vascular lesions, glomerular obsolescence and interstitial fibrosis has long been established. It should not, however, obscure the fact that renal vascular lesions can be observed in animal models as well as in some humans, especially young blacks, in the absence of, or anticipating the onset of hypertension. This leads to considering the hypothesis that nephroangiosclerosis might stem from a genetic defect in the renal vascular bed and that this defect is strongly associated with the hypertensive trait. Atherosclerotic renal disease is a major, potentially treatable cause of chronic renal disease is a major, potentially treatable cause of chronic renal failure, especially in whites. It leads to renal atrophy, but the ischemic kidney retains a vigorous potential for tubular cell regeneration, which pleads for early recognition and treatment. Recent data suggest that renal ischemia, be it due to renal artery stenosis or to cholesterol crystal embolism, ranks among the multiple causes of secondary focal segmental glomerulosclerosis. Irrespective of its initial mechanism, ischemia induces renal fibrosis, the pathophysiology of which is centered on increased generation of angiotensin II. Finally, renal vascular lesions are commonly observed in the course of various nephropathies, even in the absence of hypertension, and the relationship between these lesions and the unfavorable prognosis of glomerulopathies, especially primary focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis, remains to be elucidated. Expanding knowledge of the spectrum of nephrovasculopathies opens perspectives for investigating, understanding and treating a major mechanism of progressive renal insufficiency.
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PMID:Ischemic renal diseases: new insights into old entities. 964 58

The effects of hypercholesterolemia on ischemic renal failure were evaluated in rats subjected to 60 min of left renal artery clamping and contralateral nephrectomy. One group of rats (HC) was kept on a cholesterol-supplemented diet for 3 weeks before renal injury and compared to a group fed a regular diet (ND). Two days after renal ischemia, inulin clearance (C(in), ml/min per 100 g BW) was lower in HC-rats (0.033 +/- 0.011) than in ND-rats (0.227 +/- 0.037; P < 0.01). indicating that hypercholesterolemia potentiated renal ischemic injury. Twenty-one days after renal ischemia the C(in) of HC-rats did not differ from ND-rats, suggesting that hypercholesterolemia did not limit late recovery. Since nitric oxide production is impaired in HC, L-arginine (50 mg/kg BW i.v.) was administered immediately after ischemia. Two days after ischemia, L-arg did not protect ND-rats from ischemia, while the C(in) and renal blood flow were higher in L-arg-treated HC rats than in untreated HC rats (C(in) = 0.125 +/- 0.013 rats vs. 0.033 +/- 0.011; P < 0.001) (RBF = 3.96 +/- 0.64 vs. 2.40 +/- 0.20 ml/min per 100 g BW; P < 0.05), indicating that L-arg protects HC rats from renal ischemia. The administration of D-arginine to ND rats induced a significant decrease of the C(in) and a significant increase of FE H2O, FE Na and FE K compared to the L-arginine and not treated groups. Cultures of inner medullary collecting duct cells from ND rats were resistant to 24-h hypoxia. In contrast, IMCD cell cultures from HC rats showed higher LDH release after 24-h hypoxia than normoxic cells (69.2 +/- 3.4 vs. 30.9 +/- 3.6%, P < 0.001); 1 mM L-arg added to the medium attenuated LDH release (44.3 +/- 2.4%, P < 0.01). These data demonstrate that HC predisposes renal tubular cells to hypoxic injury and L-arg protects cells of HC.
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PMID:Protective effect of L-arginine on hypercholesterolemia-enhanced renal ischemic injury. 1021 61

Determinations of renal clearance of fluorescein isothiocyanate (FITC)-inulin were used for assessing the glomerular filtration rate (GFR) in rats and to characterize factors influencing the glomerular filtration capacity. In anesthetized rats, GFR develops after birth up to day 30. Thereafter, GFR remains relatively constant for up to 3 months of age and drops continuously until the 8th month. GFR can be determined in utero, already one day before birth, however, only at a very low level. It increases significantly on the first day of life. Even at this time the effect of furosemide on GFR can be proven. After reduction of renal mass, GFR is decreased in dependence on the extent of kidney tissue removal. However, within 2 days after unilateral nephrectomy (NX) or one week after 5/6 NX, GFR reaches values about 3/4 of the controls with two intact kidneys. Furthermore, the compensation of GFR after renal ischemia reaches 80% of baseline values after one week. On the other hand, GFR is enhanced after bile duct ligation as a model of hepato-renal failure. It has been shown in previous experiments that pretreatment with hormones can stimulate renal tubular transport processes. Pretreatment with dexamethasone or triiodothyronine after 5/6 NX improves glomerular filtration capacity whereas in animals with ligated bile ducts dexamethasone seems to prevent the increase in GFR. After subchronic treatment with epidermal growth factor (EGF) GFR is significantly reduced. A continuous infusion of amino acids does not change GFR in the controls but enhances the filtration capacity in EGF-treated rats. But immediately after bolus injection of amino acids GFR also increases significantly in the controls. Diuretics such as furosemide, most nephrotoxic agents (cyclosporine A [CsA], heavy metals) and imidazole reduce the GFR significantly. Diltiazem reported to act nephroprotectively in CsA nephrotoxicity in human beings was without beneficial effect in rats. This could be due to species differences in GFR because the rat is one of the species with the highest glomerular filtration capacity.
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PMID:Determination of the glomerular filtration rate (GFR): methodological problems, age-dependence, consequences of various surgical interventions, and the influence of different drugs and toxic substances. 1063 78

Atherosclerotic narrowing of the renal arteries may result in severe consequences including chronic renal ischemia, renal artery atheroembolism and renal vascular hypertension. Ischemic renal disease is increasingly recognised as a potentially treatable cause of chronic renal failure. Its precise prevalence is still poorly determined as there is no population based studies. The patients with ARD, particularly those with high grade stenosis and systolic hypertension are at very high risk for renal atrophy and renal failure. Angiogram is usually required to confirm the diagnosis. However, the diagnosis is likely in the elderly patient with systemic atherosclerosis and hypertension in whom a rapid rise in serum creatinine concentration is associated with decreased renal length. Disease is associated with high mortality when treated medically. In contrast, clinical improvement is reported after renal revascularisation. Therefore, consider the diagnosis in the patients at risk, because revascularisation (surgical or endovascular) can successfully preserve renal function in selected patients.
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PMID:Ischemic nephropathy. 1086 22

The positive effect of insulin-like growth factor I (IGF-I) on the outcome of experimental acute renal failure has gained much attention in recent years. However, the potential positive effects of GH have been less intensively studied. Therefore, a study was designed in which rats suffering from post-ischemic renal failure were treated with high dosage growth hormone (GH). Forty-six rats were subjected to bilateral renal ischemia for 45 min. Following reperfusion the animals were treated with either human recombinant GH in a dosage of 2 mg/day given as subcutaneous injection or placebo. The animals were monitored daily for body weight, s-creatinine, s-urea and B-glucose. S-IGF levels were determined at the start of the experiment and at days 3 and 7. IGF-I and GH receptor mRNA were measured in the kidney and the liver of the surviving animals at the end of the experiment. Survival in the GH-treated rats was 42.9% as compared to 32.0% in the control group (not significant). Both groups of animals lost body weight in the initial phase. The loss in body weight was less pronounced for the GH-treated animals and the difference was significant at day 2 (P<0.05). The s-creatinine levels tended to be lower in the GH-group at all times studied, but the difference was not significant. The s-urea levels were significantly reduced by GH-treatment at day 2 (P<0.05). GH treatment caused no adverse effects on carbohydrate metabolism as studied by daily B-glucose determinations. The serum IGF-I levels were identical in both the groups at day zero. At day 3 the serum IGF-I levels had increased by approximately 30% in both groups. At day 7 the serum IGF-I level was 1600 ng/ml in the GH-treated group as compared to 1400 ng/ml in the placebo group (not significant). When placebo-treated uremic rats were compared to normal sham-operated animals GH-rec mRNA was down-regulated in the kidney and liver, while IGF-I mRNA was down-regulated only in the liver (P<0.05). GH treatment partly restored the GH-rec and IGF-I mRNA levels in both organs. The data are compatible with a severe GH resistance syndrome in acute renal failure.
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PMID:High dosage growth hormone treatment and post-ischemic acute renal failure in the rat. 1098 82

In a neutrophil-dependent model of acute postischemic renal failure (APRF), eliminating or blocking P-selectin reduces postischemic neutrophil infiltration and preserves kidney function. This study was designed to identify the role of platelet vs. endothelial P-selectin in APRF. Using wild-type (wt) and P-selectin-deficient (P-/-) mice, we generated chimeric mice by bone marrow transplantation. Chimeric mice exclusively expressed either platelet (Plt-P) or endothelial P-selectin (EC-P). APRF was induced by bilateral renal ischemia in situ (32 min), followed by reperfusion; 48 h after reperfusion, EC-P had significantly lower creatinine concentrations (twofold over sham) than Plt-P (eightfold over sham). Compared with wt, protection from renal failure in EC-P was similar to that observed in P-/-. Plt-P and EC-P demonstrated similar overall postischemic neutrophil infiltration as measured by renal myeloperoxidase activity. However, Plt-P showed massive neutrophil infiltration into outer and inner medulla, similar to that in wt. EC-P had only patchy, more diffuse neutrophil influx. Our study identifies platelet P-selectin as crucial for postischemic neutrophil recruitment into outer and inner medulla, which is detrimental to the development of APRF. This suggests that novel therapeutic strategies for postischemic organ failure could be aimed at neutrophil-platelet interactions.
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PMID:Platelet, but not endothelial, P-selectin is critical for neutrophil-mediated acute postischemic renal failure. 1168 59

The effects of furosemide administered at the onset of postischaemic renal failure were investigated in Sprague-Dawley rats one month after exposing the left kidney to 45 min of renal ischemia. In the experimental group, 13 mg furosemide was given intravenously both before and a few minutes after induction of the ischaemia and then, by an osmotic pump, in a daily dose of 2-3 mg for the following 7 days. The animals of the control group were treated similarly but with saline alone. After one month, the glomerular filtration rate (GFR) in the damaged left kidneys of the furosemide-treated rats was 0.5+/-0.08 ml/min, which was not significantly different from that in the untreated control rats, of 0.8+/-0.14 ml/min. As expected, the right intact kidneys responded with an increase in GFR to about 2 ml/min. Further effects that were similar in the damaged kidneys of the furosemide-treated and untreated animals were a decrease in potassium secretion and in the urine concentration ability; the urine osmolality in the diseased left kidneys was thus 1000-1500 mOsm/kg, as against over 2000 mOsm/kg in the right, intact kidneys. The function of the individual nephrons in terms of such variables as single nephron filtration rate, fractional fluid reabsorption and tubular and vascular hydrostatic pressures remained unaltered, however. Hence, the severe reduction in whole kidney GFR appeared to be due to a loss of nephrons rather than to an equal decrease in each individual nephron. It is also clear that furosemide did not improve the long-term outcome of acute postischaemic renal failure.
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PMID:Failure of loop diuretics to improve the long term outcome of ischaemic damage in rat kidneys. 1188 71

Fenoldopam is an interesting orphan drug that is a variant of dopamine. It differs significantly from dopamine in that it is a specific agonist for the type I (DA-1) receptor. The DA-1 receptors are particularly prominent in the renal vasculature, renal tubules, mesenteric vasculature, and peripheral vessels. The DA-1 receptor stimulation vasodilates renal and peripheral vessels, causing a decrease in blood pressure and an increase in renal blood flow (RBF). Stimulation of the DA-1 receptors in the tubules causes an increase in sodium excretion, which gives rise to an increase in urine volume on the basis of a sodium natriuresis. Animal testing with fenoldopam has indicated that it is 6 times more potent than dopamine in its ability to decrease renal vascular resistance and increase RBF; this suggests that it could be a much more selective and potent renal protective agent against any toxin or stimulus that causes renal dysfunction by reducing RBF or increasing renal ischemia. The clinical activity of fenoldopam, which is administered intravenously, begins almost immediately and is clearly noticeable after 5 minutes. The drug has no rebound effect, and its use can be stopped at any time. The protocol for the use of fenoldopam as a renal protective agent (performed at the University of Minnesota) involves starting an intravenous fenoldopam infusion 2 hours before the procedure at a rate of 0.1 microg/kg/min and increasing the dose in increments of 0.1 microg/kg/min every 20 minutes, until a rate of 0.5 microg/kg/min is reached or the systolic blood pressure falls more than 40 mm Hg (or below 110 mm Hg). Any infusion level at or above 0.1 microg/kg/min is considered acceptable because the response in individual patients varies so widely. The fenoldopam infusion is maintained at the maximum rate throughout the procedure and for up to 4 hours after the end of the contrast administration. At the University of Minnesota, we have had anecdotal experience using the drug in 29 patients. The drug was used for patients who were thought to be at the highest risk for contrast-induced nephropathy, ie, patients who have both diabetes and pre-existing renal failure. In this small group of patients in whom hydration and other variables were not controlled, there was a startling lack of contrast-induced creatinine increase at any point during the 24 to 48 hours after the administration of contrast in all but 1 patient. Our experience suggests that fenoldopam may be of distinct benefit to high-risk patients who need intravascular contrast, especially those who may receive a large contrast dose, such as patients undergoing peripheral or coronary angiography and intervention and/or computed tomography. Although it is impossible on the basis of simple anecdotal case reports to determine whether or not the drug was the primary reason that such a marked protective effect was seen, the results are promising enough to indicate that a careful, prospective, randomized trial of fenoldopam versus hydration is warranted.
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PMID:Preventing contrast-induced nephropathy with fenoldopam. 1198 89


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