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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The elucidation of the pathogenesis of human renal disease at the molecular level has been facilitated by the growing field of gene targeting and the development of mouse strains with single-gene deletions - the 'knock-out' mice. Experimental nephrology, therefore, requires well-characterized and reliable models of human renal disease that can be induced reproducibly in mice. Today surgical procedures for the induction of renal ischemia, chronic renal failure, and ureter obstruction are feasible in mice. Models of mesangioproliferative or crescentic glomerulonephritis, glomerulosclerosis, and tubulointerstitial disease are readily available; however, these depend heavily on the mouse genetic background. Attention to the genetic background and appropriate backcrossing are, therefore, of great importance in the design and interpretation of experimental studies, especially in transgenic mice. Simple murine models displaying the clinical features of other human renal diseases such as IgA nephropathy, membranous glomerulonephritis, and renal vasculitis are still lacking. Mouse strains that spontaneously develop distinct renal pathologies similar to lupus nephritis and focal-segmental glomerulosclerosis can be intercrossed with transgenic mice to study the impact of single-gene deletions on the renal phenotype. The present review provides a survey about currently available spontaneous and inducible murine models of renal disease with special attention to problems and future perspectives for their use in transgenic animals.
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PMID:Murine models of renal disease: possibilities and problems in studies using mutant mice. 1094 Jul 15

The essential arterial hypertension is the second (after diabetes mellitus) cause of chronic renal failure which means a great social and economic burden to the society. It is well known that hypertension is a metabolic syndrome resulting in tissue injury. We tried to investigate the possible influence of some metabolic disturbances on renal function in nontreated essential hypertension. We have compared 25 patients with nontreated essential hypertension (11 women, 14 men) with 14 healthy volunteers (7 women, 7 men) matched for age. The patients' group was characterized by significantly higher urine excretion of NAG (N-acetyl-beta-D-glucosaminidase) (2.75 +/- 1.69 vs 1.82 +/- 1.46 p < 0.05) and a tendency to significantly higher urine fractional sodium excretion without significant difference in albumin excretion. These findings suggest that the tubular damage is present. We noticed the negative linear correlation between mean arterial pressure and (MAP) and NAG urine excretion in the group of hypertensive patients which may reflect the renal ischemia in tubulo-interstitial pathology. Our data suggests that in nontreated arterial hypertension the renal blood flow disturbances are the important cause of the deterioration of tubular function (which are earlier to glomerular damage).
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PMID:[Does any relationship exist between metabolic disturbances and some markers of renal damage in patients with untreated essential hypertension?]. 1139 62

Chronic renal ischemia caused by atherosclerotic renal artery stenosis (RAS) is gaining recognition as a potentially important risk factor for cardiovascular (CV) morbidity and mortality. The etiology of increased risk of CV events is multifaceted and includes direct physiologic changes that increase risk as well as intermediate clinical effects that are associated with worse outcome. Physiologic changes associated with increased CV risk in patients with RAS include increased production of fibrogenic and vasoactive peptides such as renin, angiotensin, endothelin, and catecholamines, as well as endothelial cell dysfunction. Clinical intermediate conditions associated with higher incidences of CV events seen in patients with renal ischemia include hypertension, systemic atherosclerosis, chronic renal failure, and left ventricular hypertrophy and dysfunction. More thorough understanding of the myriad physiologic changes seen in patients with RAS will likely improve patient selection for renal artery revascularization. Clinical trials should examine a full range of CV and renal outcomes, not just blood pressure, to adequately assess the merits of revascularization.
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PMID:Chronic renal ischemia: implications for cardiovascular disease risk. 1247 Nov 81

Acute renal failure, characterized by rapid decline in glomerular filtration rate, is a major cause of morbidity and mortality. During the evolution of renal diseases chronic ischemia develops. Indeed, acute or chronic renal failure may occur as a result of renal ischemia, which induces cells to dedifferentiate, proliferate, or become apoptotic. In this study, we have investigated the expression of a newly identified transcription factor, 6A3-5, under in vitro and in vivo conditions. Proliferating vascular smooth muscle were investigated in response to different mitogenic agents. The 6A3-5 expression was then studied in ischemic rat kidney, induced by renal pedicle clamping, followed, or not, by reperfusion. Subsequently human renal biopsies from early kidney grafts and chronic renal diseases were also investigated for 6A3-5 protein expression by immunohistochemistry. In vitro study shows an over-expression of 6A3-5 following 2 to 4 hours stimulation by serum or Angiotensin II, of rat proliferating aortic smooth muscle cell. Moreover, in vivo study shows that this new protein is over expressed in rat kidney submitted to 45 minutes ischemia. An anti-6A3-5 antibody shows the protein to be expressed in smooth muscle cells of the arterioles and intermediate size arteries, in mesangial cells and interstitial myofibroblasts. In human biopsies of early kidney grafts and renal disease, the same up-regulation of 6A3-5, as in acute ischemic situation, is observed. This 6A3-5 expression is intimately associated with alpha-smooth muscle cell actin expression in mesangial cells, arteriolar smooth muscle cells as well as interstitial myofibroblasts. Transcription factor 6A3-5 could potentially be a novel early vascular marker of acute and chronic renal ischemic stress implicated in tissue remodeling.
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PMID:Ischemia induces early expression of a new transcription factor (6A3-5) in kidney vascular smooth muscle cells: studies in rat and human renal pathology. 1463 20

Sympathetic hyperactivity plays an important and distinct role in hypertension associated with chronic renal failure (CRF). Renal ischemia, elevated angiotensin II, and suppressed brain nitric oxide (NO) all stimulate sympathetic activity. Evidence is accumulating for a role of sympathetic hyperactivity in renal and cardiac damage in patients with CRF. Decreased NO availability and increased oxidative stress, characteristic in CRF patients, seem to sensitize target organs for damaging actions of sympathetic hyperactivity. Fortunately, sympatholytic agents can slow down progression of renal and cardiac dysfunction. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists suppress sympathetic activity, but complete elimination of the effect of sympathetic hyperactivity can be obtained only with specific adrenergic blockers. However, this important therapeutic option is grossly neglected, painfully illustrated by the unwillingness to treat CRF patients with beta-blockers, even if they have had a myocardial infarction. After discussion of mechanisms and effects of the sympathetic hyperactivity, a case is made for increased application of specific adrenergic blockers in patients with CRF.
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PMID:Sympathetic hyperactivity in chronic renal failure: a wake-up call. 1497 54

Much evidence indicates increased sympathetic nervous activity (SNA) in renal disease. Renal ischemia is probably a primary event leading to increased SNA. Increased SNA often occurs in association with hypertension. However, the deleterious effect of increased SNA on the diseased kidney is not only caused by hypertension. Another characteristic of renal disease is unbalanced nitric oxide (NO) and angiotensin (Ang) activity. Increased SNA in renal disease may be sustained because a state of NO-Ang II unbalance is also present in the hypothalamus. Very few studies have directly compared the efficacy of adrenergic blockade with other renoprotective measures. Third-generation beta-blockers seem to have more protective effects than traditional beta-blockers, possibly via stimulation of NO release. Although it has been extensively documented that muscle SNA is increased in chronic renal failure, data on renal SNA and cardiac SNA are not available for these patients before end-stage renal disease. It is also unknown whether additional treatment with third-generation beta-blockers can delay the progression of renal injury and prevent cardiac injury in chronic renal failure more efficiently than conventional treatment with angiotensin-converting enzyme inhibitors only.
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PMID:Causes and consequences of increased sympathetic activity in renal disease. 1498 Oct 63

Renal ischemia and reperfusion (I/R) injury is the major cause of acute renal failure and may also be involved in the development and progression of some forms of chronic kidney disease. We previously showed that a mineralocorticoid receptor (MR) blockade prevents renal vasoconstriction induced by cyclosporine that leads to acute and chronic renal failure (Feria I, Pichardo I, Juarez P, Ramirez V, Gonzalez MA, Uribe N, Garcia-Torres R, Lopez-Casillas F, Gamba G, Bobadilla NA. Kidney Int 63: 43-52, 2003; Perez-Rojas JM, Derive S, Blanco JA, Cruz C, Martinez de la Maza L, Gamba G, Bobadilla NA. Am J Physiol Renal Physiol 289: F1020-F1030, 2005). Thus we investigated whether spironolactone administration prevents the functional and structural damage induced by renal ischemia-reperfusion (I/R). Five groups were studied: sham-operated animals, rats that underwent 20 min of ischemia and 24 h of reperfusion, and three groups that received spironolactone 1, 2, or 3 days before I/R, respectively. Renal I/R produced significant renal dysfunction and tubular damage. Spironolactone administration completely prevented a decrease in renal blood flow, the development of acute renal failure, and tubular apoptosis. The protection conferred by spironolactone was characterized by decreasing oxidative stress, as evidenced by a reduction in kidney lipoperoxidation, increasing expression of antioxidant enzymes, and restoration of urinary NO(2)/NO(3) excretion. Endothelial nitric oxide synthase expression was upregulated by a mineralocorticoid receptor blockade in I/R groups; in addition, an increase in activating phosphorylation of this enzyme at residue S1177 and a decrease in inactivating phosphorylation at T497 were observed. In conclusion, our study shows that spironolactone administration prevents the renal injury induced by I/R, suggesting that aldosterone plays a central role in this model of renal injury.
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PMID:Renal ischemia-reperfusion injury is prevented by the mineralocorticoid receptor blocker spironolactone. 1737 67

Investigations into the relation between wine consumption and kidney disease have been limited. Patients with chronic renal failure show accelerated atherosclerotic damage and, considering the well-known protective effect of wine on the cardiovascular system, moderate wine consumption might be advantageous. Oxidative stress and endothelial dysfunction, which are inter-related, play a role in the pathophysiology of many renal diseases, including acute and chronic renal failure. Ethanol and non-alcoholic wine components, especially polyphenols, influence oxidative balance and endothelial function. Although long-term alcohol abuse has been associated with many renal alterations in humans, in experimental studies wine polyphenols enhanced kidney antioxidant defenses, exerted protective effects against renal ischemia/reperfusion injury, and inhibited apoptosis of mesangial cells. Moreover, in diabetic patients the administration of moderate amounts of red wine and a polyphenol-enriched diet slowed the progression of diabetic nephropathy. Moreover, the unfavorable effect of ethanol on blood pressure control seems to be counterbalanced by polyphenol protective effects. There is convincing evidence of a beneficial effect of controlled wine consumption patients with renal disease, but controlled clinical trials are needed to confirm this hypothesis.
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PMID:Wine consumption and renal diseases: new perspectives. 1757 20

Encephalopathy may accompany acute or chronic renal failure, and the mechanisms responsible for neurological complications in patients with renal failure are poorly known. Considering that creatine kinase (CK) is important for brain energy homeostasis and is inhibited by free radicals, and that oxidative stress is probably involved in the pathogenesis of uremic encephalopathy, we measured CK activity (hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex) in brain if rats submitted to renal ischemia and the effect of administration of antioxidants (N-acetylcysteine, NAC and deferoxamine, DFX) on this enzyme. We verified that CK activity was not altered in cerebellum and striatum of rats. CK activity was inhibited in prefrontal cortex and hippocampus of rats 12h after renal ischemia. The treatment with antioxidants prevented such effect. Cerebral cortex was also affected, but in this area CK activity was inhibited 6 and 12h after renal ischemia. Moreover, only NAC or NAC plus DFX were able to prevent the inhibition on the enzyme. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity after renal failure may be associated to neuronal loss and may be involved in the pathogenesis of uremic encephalopathy.
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PMID:Inhibition of brain creatine kinase activity after renal ischemia is attenuated by N-acetylcysteine and deferoxamine administration. 1830 34

Diabetes is a major epidemic, and diabetic nephropathy is the most common cause of end-stage renal disease. Two critical components of diabetic nephropathy are persistent inflammation and chronic renal ischemia from widespread vasculopathy. Moreover, acute ischemic renal injury is common in diabetes, potentially causing chronic kidney disease or end-stage renal disease. Accordingly, we tested the hypothesis that acute renal ischemia accelerates nephropathy in diabetes by activating proinflammatory pathways. Lean and obese-diabetic ZS rats (F(1) hybrids of spontaneously hypertensive heart failure and Zucker fatty diabetic rats) were subjected to bilateral renal ischemia or sham surgery before the onset of proteinuria. The postischemic state in rats with obesity-diabetes was characterized by progressive chronic renal failure, increased proteinuria, and renal expression of proinflammatory mediators. Leukocyte number in obese-diabetic rat kidney was markedly increased for months after ischemia. Intrarenal blood flow velocity was decreased after ischemia in lean control and obese-diabetic rats, although it recovered in lean rats. At 2 mo after ischemia, blood flow velocity decreased further in sham-surgery and postischemia obese-diabetic rats, so that RBC flow velocity was only 39% of control in the obese-diabetic rats after ischemia. In addition, microvascular density remained depressed at 2 mo in kidneys of obese-diabetic rats after ischemia. Abnormal microvascular permeability and increases in interstitial fibrosis and apoptotic renal cell death were also more pronounced after ischemia in obese-diabetic rats. These data support the hypothesis that acute renal ischemia in obesity-diabetes severely aggravates chronic inflammation and vasculopathy, creating a self-perpetuating postischemia inflammatory syndrome, which accelerates renal failure.
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PMID:Postischemic inflammatory syndrome: a critical mechanism of progression in diabetic nephropathy. 1965 16


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