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

Recovery from injury is usually accompanied by cell replication, in which new cells replace those irreparably damaged. After acute renal failure, normally quiescent kidney cells enter the cell cycle, which in tubule segments is accompanied by the induction of cell cycle inhibitors. We found that after acute renal failure induced by either cisplatin injection or renal ischemia, induction of the p21 cyclin-dependent kinase (cdk) inhibitor is protective. Mice lacking this gene developed more widespread kidney cell death, more severe renal failure, and had reduced survival, compared with mice with a functional p21 gene. Here, we show induction of 14-3-3sigma, a regulator of G(2)-to-M transition, after acute renal failure. Our findings, using both in vivo and in vitro models of acute renal failure, show that this protein likely helps to coordinate cell cycle activity to maximize recovery of renal epithelial cells from injury and reduce the extent of the injury itself. Because in terminally differentiated cells, these proteins are highly expressed only after injury, we propose that cell cycle coordination by induction of these proteins could be a general model of tissue recovery from stress and injury.
 ...
PMID:Coordination of the cell cycle is an important determinant of the syndrome of acute renal failure. 1221 73

A(3) adenosine receptor (AR) activation and inhibition worsen and improve, respectively, renal function after ischemia-reperfusion (I/R) injury in rats. We sought to further characterize the role of A(3) ARs in modulating renal function after either I/R or myoglobinuric renal injury. A(3) knockout mice had significantly lower plasma creatinines compared with C57 controls 24 h after I/R or myoglobinuric renal injury. C57 control mice pretreated with the A(3) AR antagonist [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5 dicarboxylate] or agonist [0.125 mg/kg N(6)-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (IB-MECA)] demonstrated improved or worsened renal function, respectively, after I/R or myoglobinuric renal injury. Higher doses of IB-MECA were lethal in C57 mice subjected to renal ischemia. H(1) but not H(2) histamine receptor antagonist prevented death in mice pretreated with IB-MECA before renal ischemia. Improvement in renal function was associated with significantly improved renal histology. In conclusion, preischemic A(3) AR activation (0.125 mg/kg IB-MECA) exacerbated renal I/R injury in mice. Mice lacking A(3) ARs or blocking A(3) ARs in wild-type mice resulted in significant renal protection from ischemic or myoglobinuric renal failure.
 ...
PMID:A3 adenosine receptor knockout mice are protected against ischemia- and myoglobinuria-induced renal failure. 1238 99

The expression of fibronectin (FN), one of the extracellular matrix proteins, was studied in isolated renal proximal tubules in a in vivo rat model of unilateral renal ischemia without reperfusion. FN is involved in cell-extracellular matrix interactions and defective cell-extracellular matrix interactions have been hypothesized to contribute to ischemic renal failure. The expression of FN was investigated by reverse transcription-polymerase chain reaction (RT-PCR), Elisa and Western blot. Isolated proximal tubules from control and post-ischemic rat kidneys were used. ATP, intracellular calcium content, and alkaline phosphatase were also measured to describe the effects associated to 40 min of ischemia. Control tubules expressed FN. Forty minutes of ischemia promoted diminished ATP levels and phosphatase alkaline activity, and increased intracellular calcium in isolated proximal tubules. An increased abundance of FN was observed by ischemic tubules as compared with control tubules. To determine quantitatively the value of FN content, ELISA method was performed. The ischemic tubules also expressed higher amount of FN mRNA. Three amplification products were obtained from both ischemic and control proximal tubular cDNA. The relative amounts of each of the obtained products were the same, strongly suggesting that the augmentation of the FN gene transcription during ischemia is not associated to a modification in the splicing pattern. Moreover, this expression is increased after 40 min of ischemia, not followed by reperfusion.
 ...
PMID:Fibronectin expression in proximal tubules from ischemic rat kidneys without reperfusion. 1248 21

Renal ischemia is of clinical interest because of its role in renal failure and also renal graft rejection. To evaluate the effect of the combination of N-acetylcysteine (NAC), a potent antioxidant, sodium nitroprusside (SNP), a nitric oxide donor, and phosphoramidon (P), an endothelin converting enzyme inhibitor, on tissue protection against ischemia-reperfusion injury, we studied the biochemical and morphological changes due to 90 min of renal ischemia-reperfusion in the rat model. Ninety min of ischemia caused very severe injury and the animals could not survive after 4 days without any treatment. Whereas, animals in the treated groups survived i.e. the NAC group (25%), NAC + SNP group (43%) and in the NAC + SNP + P group (100%), 2 weeks after 90 min of ischemia. A significant increase in the serum levels of creatinine and urea nitrogen was shown in the untreated group and to a much lesser extent in the treated group, especially in the NAC + SNP + P group. The protective effect was also supported by light microscopic studies on renal tissue sections. We also measured the activities of antioxidant enzymes in tissue homogenates. With the exception of Mn-superoxide dismutase, the activities of antioxidant enzymes (catalase, glutathione peroxidase, CuZn-superoxide dismutase) were decreased in the untreated kidney. The administration of NAC alone and NAC + SNP protected against the loss of activities. Treatment with a combination of NAC, SNP and P showed a synergistic effect as evidenced by the best protection. These results suggest that pre-administration of a combination of antioxidant (NAC) with endothelin derived vasodilators (sodium nitroprusside and Phosphoramidon) attenuates renal ischemia-reperfusion injury, e.g. in donor kidney for transplantation, by protecting cells against free radical damage.
 ...
PMID:Combination therapy of N-acetylcysteine, sodium nitroprusside and phosphoramidon attenuates ischemia-reperfusion injury in rat kidney. 1248 67

Acute renal failure results in significant morbidity and mortality, yet renal failure is not the usual cause of death in the clinical situation. We have previously reported systemic increases in the inflammatory mediators tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) after renal ischemia in the mouse. In the present study, an animal model of bilateral renal ischemia was used to test the hypothesis that cytokines released with renal ischemia have effects on other organ systems. Increased levels of immunoreactive TNF-alpha and IL-1 and intercellular adhesion molecule-1 mRNA were found in the heart after renal ischemia in the rat. This was accompanied by increases in myeloperoxidase activity, an index of tissue leukocyte infiltration, in the heart as well as the liver and lung. Functional changes in the heart 48 h after renal ischemia included increases in left ventricular end diastolic diameter, left ventricular end systolic diameter, and decreased fractional shortening by echocardiography. Evidence of apoptosis of cardiac cells was also found 48 h after an abbreviated period of renal ischemia insufficient to induce azotemia but not bilateral nephrectomy (which resulted in significant renal failure), suggesting that renal ischemia but not uremia is necessary for the apoptosis observed. It was also found that blocking the action of TNF-alpha limited cardiac apoptosis. Renal ischemia results in distant effects and the alterations observed in the heart may be important in the morbidity and mortality observed clinically.
 ...
PMID:Distant effects of experimental renal ischemia/reperfusion injury. 1276 Dec 55

Autosomal dominant polycystic kidney disease (ADPKD), a common genetic disease, is characterized by the development of hypertension and end stage renal disease. An increase in the activity of the renin-angiotensin system, due to a renal ischemia caused by cyst expansion, contributes to the development of hypertension and renal failure in ADPKD. Recently, the angiotensinogen (AGT) gene, M235T, and angiotensin II type 1 receptor (ATR) gene, A1166C, polymorphisms have been associated with the susceptibility to develop hypertension and renal disease. We hypothesized that the AGT M235T and ATR A1166C polymorphisms could account for some of the variability in the progression of ADPKD. Genotyping was performed in 108 adult patients with ADPKD, and 105 normotensive healthy controls, using PCR and restriction digestion. We analyzed the effects of the AGT M235T and ATR A1166C polymorphisms on hypertension and age at the end stage renal disease (ESRD). Of the 108 patients with ADPKD, 64 (59%) had hypertension and 24 (22%) reached the ESRD. The prevalence of hypertension were; [MM+MT], [TT] genotypes, 60%, 59% (p=1.00); [AA], [AC+CC] genotypes, 60%, 50% respectively (p=0.54). The ages at the onset of ESRD were; [MM+MT], [TT] genotypes, 50 +/- 9 years, 56 +/- 8 years (p=0.07); [AA], [AC+CC] genotypes, 54 +/- 8 years, 52 +/- 14 years, respectively (p=0.07). There were no differences in the prevalence of hypertension and the ages at the ESRD in relation to the AGT M235T and ATR A1166C polymorphisms. We suggest that the AGT and ATR gene polymorphisms would not have an effect on hypertension or the ESRD in ADPKD.
 ...
PMID:Angiotensinogen and angiotensin II type 1 receptor gene polymorphism in patients with autosomal dominant polycystic kidney disease: effect on hypertension and ESRD. 1295 Jan 20

Since hepatorenal syndrome is a functional renal failure due to renal ischemia in cirrhotics with refractory ascites, we investigated whether increased intra-abdominal pressure (IAP) impairs the renal function and perfusion in cirrhotic portal hypertensive rats. Eight groups of 32 rats each were studied, including 4 control and 4 CCl(4) cirrhotic groups. These were subdivided into two groups each, with and without an increased IAP, and further subdivided into groups of rats with and without NO inhibition. IAP was increased to 20 mm Hg for 7 consecutive days by means of an intraperitoneally placed balloon filled with water. The animals were studied in normal conditions and after inhibition of NO synthesis. Changes in mean arterial pressure and renal microcirculation by means of femoral artery catheterization and laser-Doppler technique, respectively, were recorded. Venous samples for determination of plasma renin-aldosterone activity, biochemical parameters of liver and renal function, and plasma nitrite/nitrate levels as an index of NO synthesis were drawn. Cirrhotic rats showed decreased renal microcirculation (P = 0.05), while elevated IAP produced a further decrease (P = 0.01). Renin-aldosterone levels found increased (P = 0.001) in cirrhotics, and elevated IAP produced a further increase (P = 0.01] in both groups. Inhibition of NO synthesis resulted in a nonsignificant decrease in both renal microcirculation and renin-aldosterone levels in all experimental groups. Liver and renal function was found to be impaired in cirrhotics, but increased IAP had a nonsignificant further functional impairment in both organs. In conclusion, chronically elevated IAP in cirrhotic rats is associated with an increase in renin-aldosterone levels and significant impairment of renal perfusion.
 ...
PMID:The influence of continuous seven-day elevated intra-abdominal pressure in the renal perfusion in cirrhotic rats. 1457 84

The major message from this discussion is that the end points from hypertensive disease (stroke, CHD, and hypertensive emergencies) are now preventable. Cardiac failure and ESRD, however, two exceedingly common end points from long-standing hypertension, remain as major disabilities and causes of death. The former is the most common cause of hospitalization in industrialized societies; hypertension and diabetes mellitus are the most common causes of the latter. The mechanisms of risk of these target organ diseases is not LVH per se, or the elevated arterial pressure alone in the kidney, but the coronary and renal ischemia, organ fibrosis, and, perhaps, apoptosis. Present day therapy now can effectively reverse these costly (economically and by human suffering) complications. Recent experimental studies suggest that, when used early enough, these newer pharmacologic agents may even prevent their occurrences and consequences. The very practical lesson from these experiences is that early detection and treatment of hypertension, effective control of arterial pressure, and the suppression of the underlying disease mechanisms markedly reduce the now increasing prevalence of both cardiac and renal failure.
 ...
PMID:Target organ involvement in hypertension: a realistic promise of prevention and reversal. 1487 Oct 60

Hepatorenal syndrome is functional, reversible renal failure that occurs in patients with advanced liver cirrhosis or acute hepatic failure. The fundamental problem in hepatorenal syndrome is renal ischemia secondary to hypotension and profound renal cortical vasoconstriction. Sinusoidal hypertension and its associated splanchnic arterial vasodilatation initiate a cascade of events leading to activation of systemic and local vasoconstrictors and depletion of local renal vasodilators. Therapy with vasopressin V(1) receptor and alpha-adrenergic agonists, and plasma expanders, reverses type I and type II hepatorenal syndrome and improves survival. Large randomized, controlled, multicenter trials are needed to determine which drug is most effective, as well as the optimal dose and duration of treatment.
 ...
PMID:Hepatorenal syndrome: pathogenesis and novel pharmacological targets. 1506 65

Renal toxicity of contrast agents remains an up-to-date challenge. N'Acetyl cystein is an antioxyde agent which efficacy has been proved in various models of experimental renal ischemia and therefore proposed in the prevention of renal failure due to intravenous iodine contrast media. The Author of this review reports and comments these studies in order to better define indications of N'Acetyl cystein in this clinical context.
 ...
PMID:[Value of N-acetylcysteine to prevent nephrotoxicity from iodinated contrast agents]. 1524 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>