Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main functional change in patients with acute renal failure (ARF) is a decrease in glomerular filtration rate (GFR). The virtual complete recovery of renal function in those patients who survive ARF, as well as the minimal renal histological abnormalities during ARF when the GFR is less than 10 ml/min, suggest that a major component of the renal tubular cell injury is sublethal or reversible. Experimental models of acute tubular necrosis frequently have placed the emphasis on irreversible proximal tubular cell death. The nature of the renal tubular cell injury in ischemic acute renal failure, however, includes not only cell death (necrosis or apoptosis) but also sublethal injury causing cell dysfunction. The role of intracellular calcium, the calcium-dependent enzymes calpain, phospholipase A2 and nitric oxide synthase (NOS), in the pathophophysiology of this renal tubular cell injury during hypoxia/ischemia is described. The effects of calpain and nitric oxide (NO) on the cytoskeleton and cell adhesion are discussed. Potential mechanisms whereby tubular injury leads to a profound fall in GFR, including increased tubuloglomerular feedback and increased distal tubular obstruction, in ischemic acute renal failure are proposed.
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PMID:The nature of renal cell injury. 915 Apr 42

Mercury chloride (HgCl2) has a potent nephrotoxic effect. Most of Hg2+ existing in plasma following HgCl2 exposure forms a complex with sulfhydryl-containing ligands such as albumin and glutathione (GSH). The Hg(2+)-GSH complex is filtered in the glomeruli of the kidney and degraded into Hg(2+)-cysteine in the proximal tubules by the combined action of gamma-glutamyl transpeptidase and dipeptidase present in the epithelial cells. The degradation product is then incorporated and accumulated into the proximal tubule epithelial cells. The accumulated Hg2+ in the epithelial cells finally causes acute tubular necrosis (ATN) by its cytotoxic effect. At present, it is believed that tubular obstruction resulting from ATN triggers the onset of HgCl2-induced acute renal failure (ARF). A progressive fall in glomerular filtration rate (GFR) contributes to the progression of HgCl2-induced ARF. The fall in GFR may be caused by an increment in afferent arteriole resistance (RA) and a decrement in the ultrafiltration coefficient (Kf) due to mesangial cell contraction. These changes in RA and Kf may be attributed to the increased action of the vasoconstrictors, angiotensin II and endothelin-1 and to the decreased action of the vasodilator, nitric oxide observed at the glomerulus level of HgCl2-induced ARF. Accordingly, the imbalance between these vasoactive substances appears to play an important role in the progression of HgCl2-induced ARF due to reducing GFR. Further studies, however, remain to elucidate the mechanisms involved.
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PMID:[HgCl2-induced acute renal failure and its pathophysiology]. 952 59

The systemic symptoms, tissue lesions and release of cytokines were analysed in four isogenic mouse strains with distinct haplotypes injected with various doses of Loxosceles intermedia spider venom. The estimated LD50 were 24.5 microg for C57Bl/6, 17.6 microg for BALB/c, 6.3 microg for C3H/HeJ and 4.6 microg for A/Sn mice. Prostration, acute cachexia, hypothermia, neurological disorders and hemoglobinuria were the signals preceding death. Accumulation of eosinophilic material inside the proximal and distal renal tubules and acute tubular necrosis were the most common histopathological findings. Death was prevented by previous treatment of venom with specific antivenom serum. The protein F35 purified from the whole venom retained the ability to induce the symptoms of the whole venom. The cytokines tumor necrosis factor (TNF), interleukins IL-6 and IL-10 and the radical nitric oxide were detected in serum at different levels after venom injection. These findings indicate that the state of shock produced in mice by whole endotoxin-free L. intermedia venom or by its purified fraction, protein F35, mimics the endotoxemic shock, that susceptibility to the systemic effects of the venom varies among mice of different haplotypes and that the pattern of in vivo cytokine release resembles that of endotoxemic shock.
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PMID:Endotoxemic-like shock induced by Loxosceles spider venoms: pathological changes and putative cytokine mediators. 962 May 87

Research during the last few years has uncovered the mechanisms responsible for acute renal failure. During the initiation phase of acute tubular necrosis sublethal injury, apoptosis or necrosis of the tubular epithelium, hemodynamic alterations, tubule obstruction and back leakage occur. Hypofiltration persists due to imbalance between endothelins and endothelium derived nitric oxide, medullary congestion and tubuloglomerular feedback. Recovery is characterised by tubular epithelium regeneration. A greater understanding of the pathogenesis of acute renal failure will allow better management of such cases.
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PMID:Evolving trends in the etiopathogenesis of acute renal failure. 1119 92

Gentamicin is still widely used in clinical practice in spite of its renal toxicity. The role of nitric oxide (NO) in that process is not completely elucidated. The aim of this study was to investigate the relationship between plasma level of NO and the histopathological changes of kidney in acute tubular necrosis (ATN) induced by gentamicin in rats. Study was carried out in Albino-Wistar rats, both sexes (n=16), average body weight 200-250 g. divided in two equal groups: control and gentamicin group. The control group was injected with 0.9% NaCl i.p. and gentamicin group was injected with gentamicin in the dose of 80 mg/kg/day i.p. in a period of 5 consecutive days. NO plasma level was determined by the production of nitrates and nitrites using classical colorimetrical Griess reaction. Kidney specimens were stained with hematoxylin-eosin (H-E) and Periodic acid-Schiff (PAS) stain. Semiquantitative histological analysis was used for the evaluation of the level of kidney damage. Both, the plasma NO level and the level of kidney damage were statistically higher in rats with gentamicin-induced ATN in comparison to the control group. In spite of that the correlation between plasma NO level and the level of kidney damage was not found. The rise of plasma level NO in gentamicin induced ATN in rats could possibly indicate on the role of NO in renal damage caused by gentamicin.
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PMID:Nitric oxide in gentamicin-induced acute tubular necrosis in rats. 1605 59

The clinical detection of evolving acute tubular necrosis (ATN) and differentiating it from other causes of renal failure are currently limited. The maintenance of the corticomedullary sodium gradient, an indicator of normal kidney function, is presumably lost early in the course of ATN. Herein, sodium magnetic resonance imaging (23Na MRI) was applied to study the early alteration in renal sodium distribution in rat kidneys 6 h after the induction of ATN. Three-dimensional gradient echo sodium images were recorded at 4.7 T with high spatial resolution. ATN was produced by the administration of radiologic contrast medium, combined with inhibition of nitric oxide and prostaglandin synthesis. The sodium images revealed that the sham-controlled kidney exhibited a linear increase in sodium concentration along the corticomedullary axis of 30+/-2 mmol/l/mm, resulting in an inner medulla to cortex sodium ratio of 4.3+/-0.3 (n=5). In the ATN kidney, however, the cortico-outer medullary sodium gradient was reduced by 21% (P<0.01, n=7) and the inner medulla to cortex sodium ratio was decreased by 40% (P<0.001, n=7). Small, though significant, increments in plasma creatinine at this time inversely correlated with the decline in the corticomedullary sodium gradient. Histological findings demonstrated outer medullary ATN involving 4% of medullary thick ascending limbs. Hence, 23Na MRI non-invasively quantified changes in the corticomedullary sodium gradient in the ATN kidney when morphologic tubular injury was still focal and very limited. MRI detection of corticomedullary sodium gradient abnormalities may serve to identify evolving ATN at its early phases.
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PMID:Detection of evolving acute tubular necrosis with renal 23Na MRI: studies in rats. 1651 33

Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney injury in hospitalized patients and is associated with significant patient morbidity. The pathogenesis of CIN is complex and not fully understood, but iodinated contrast agents induce intense and prolonged vasoconstriction at the corticomedullary junction of the kidney. Moreover, high-osmolar dyes directly impair the autoregulatory capacity of the kidney through a loss of nitric oxide production. These effects, coupled with direct tubular toxicity of contrast media, lead to overt acute tubular necrosis and the syndrome of CIN.
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PMID:Pathophysiology of contrast-induced nephropathy. 1694 76

Oxidative stress is important in the pathogenesis of renal ischemia-reperfusion (IR) injury; however whether imbalances in reactive oxygen production and disposal account for susceptibility to injury is unclear. The purpose of this study was to compare necrosis, apoptosis, and oxidative stress in IR-resistant Brown Norway rats vs. IR-susceptible Sprague-Dawley (SD) rats in an in vivo model of renal IR injury. As superoxide (O (2) (.-) ) interacts with nitric oxide (NO) to form peroxynitrite, inducible NO synthase (iNOS) and nitrotyrosine were also examined. Renal IR was induced in SD and BN rats by bilateral clamping of renal arteries for 45 min followed by reperfusion for 24 h (SD 24 and BN 24, respectively). BN rats were resistant to renal IR injury as evidenced by lower plasma creatinine and decreased acute tubular necrosis. TUNEL staining analysis demonstrated significantly decreased apoptosis in the BN rats vs. SD rats after IR. Following IR, O (2) (.-) levels were also significantly lower in renal tissue of BN rats vs. SD rats (P < 0.05) in conjunction with a preservation of the O (2) (.-) dismutating protein, CuZn superoxide dismutase (CuZn SOD) (P < 0.05). This was accompanied by an overall decrease in 4-hydroxynonenal adducts in the BN but not SD rats after IR. BN rats also displayed lower iNOS expression (P < 0.05) resulting in lower tissue NO levels and decreased nitrotyrosine formation (P < 0.01) following IR. Collectively these results show that the resistance of the BN rat to renal IR injury is associated with a favorable balance of oxidant production vs. oxidant removal.
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PMID:Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury. 1745 15

Renal ischemia-reperfusion (I-R) contributes to the development of ischemic acute renal failure (ARF). Multi-factorial processes are involved in the development and progression of renal I-R injury with the generation of reactive oxygen species, nitric oxide and peroxynitrite, and the decline of antioxidant protection playing major roles, leading to dysfunction, injury, and death of the cells of the kidney. Renal inflammation, involving cytokine/adhesion molecule cascades with recruitment, activation, and diapedesis of circulating leukocytes is also implicated. Clinically, renal I-R occurs in a variety of medical and surgical settings and is responsible for the development of acute tubular necrosis (a characteristic feature of ischemic ARF), e.g., in renal transplantation where I-R of the kidney directly influences graft and patient survival. The cellular mechanisms involved in the development of renal I-R injury have been targeted by several pharmacological interventions. However, although showing promise in experimental models of renal I-R injury and ischemic ARF, they have not proved successful in the clinical setting (e.g., atrial natriuretic peptide, low-dose dopamine). This review highlights recent pharmacological developments, which have shown particular promise against experimental renal I-R injury and ischemic ARF, including novel antioxidants and antioxidant enzyme mimetics, nitric oxide and nitric oxide synthase inhibitors, erythropoietin, peroxisome-proliferator-activated receptor agonists, inhibitors of poly(ADP-ribose) polymerase, carbon monoxide-releasing molecules, statins, and adenosine. Novel approaches such as recent research involving combination therapies and the potential of non-pharmacological strategies are also considered.
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PMID:Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review. 1803 25

Insulinlike growth factor I (IGF-I), IGF-I receptors, and IGF-binding proteins are expressed in different segments of the nephron in a relationship that suggests autocrine, paracrine, and endocrine modes of action. IGF-I contributes to compensatory nephron growth in a variety of experimental renal diseases with loss in functioning nephron number, and to tissue repair after ischemic acute tubular necrosis. IGF-I causes arteriolar dilatation in the kidney and increases the glomerular filtration rate in experimental animals, in normal subjects, as well as in patients with chronic renal failure, and this effect of the peptide is probably mediated by nitric oxide. IGF-I raises proximal tubular phosphate reabsorption and may increase sodium absorption in distal tubules. In the nephrotic syndrome, IGF-I- and IGF-binding protein complexes are excreted in urine and IGFBP-3 protease activity is increased, causing complex abnormalities in the IGF-system.
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PMID:Insulinlike growth factor I and the kidney. 1840 31


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