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)

Paraquat (PQ) toxicity produces severe injures in many major organs systems, including kidney, developing renal failure with fatal evolution in most of the cases. Several antidotes have been used in the treatment of paraquat intoxication without satisfactory results. The antioxidative effect of melatonin (MLT) and sodium thiosulphate (STS) on kidney in rats with acute intoxication by PQ was studied. Forty male Wistar rats were used, divided in 4 groups of 10 rats each. Group I, control, was injected intraperitoneally (ip) with 1 ml of saline solution; group II, received DL50 of PQ, ip; groups III and IV, DL50 of PQ, and simultaneously the first dose of MLT (15 mg/kg, ip) or STS (1,5 g/kg, i.p.) respectively. Thirty minutes later, groups III and IV received a second similar dose of MLT and TSS. After 24 hours, rats were sacrificed with pentobarbital, and kidneys were extracted for morphological study. Light and electronic microscopy observations showed in group II morphological changes of acute tubular necrosis in proximal tubule in group II, similar findings, with lesser magnitude, were observed in the animals treated with the antidotes, suggesting a partial protection. In conclusion, individual use of MLT and STS at the doses and time used partially prevent damage caused by paraquat to the cell. In consequence, more experiments with these drugs are necessary to considere them as specific treatments in cases of poisoning by paraquat.
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PMID:[Protective effect of melatonin and sodium thiosulphate on histopathology and ultrastructure of the kidney in rats with acute paraquat poisoning]. 1743 46

Glycerol-induced renal lesions can have many causes, including increased oxidative stress and inflammation. Resveratrol, a polyphenolic phytoalexin found in grapes and red wine, is an antioxidant agent with anti-inflammatory effects. In the present study, we investigated the possible protective effect of resveratrol on glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8 ml/kg of either 50% glycerol (n=18), glycerol+resveratrol (n=22), 0.15 M saline (n=14), saline+carboxymethylcellulose (n=10) or saline+resveratrol (n=8). The rats were killed 3 days after the injections, at which time the kidneys were removed for histological and immunohistochemical studies and lipid peroxidation determination. Blood and urine samples were collected in order to quantify sodium and creatinine. The results of the histological and immunohistochemical studies were scored according to the extent of damage and immunostaining, respectively, in the cortical tubulointerstitium. Lipid peroxidation was estimated by measuring malondialdehyde in renal tissue samples collected from control rats and glycerol-injected rats. By postinjection day 3, glycerol-only treated rats presented increases in plasma creatinine levels, as well as in fractional excretion of sodium and potassium (P<0.001). These increases were less pronounced in glycerol+resveratrol-treated rats (P<0.05). Cortical expression of macrophages, lymphocytes, nuclear factor-kappa B, heme oxygenase-1 and nitrotyrosine was greater in glycerol-treated rats than in controls (P<0.001). In addition, the histological findings for glycerol-treated rats were characteristic of acute tubular necrosis. Resveratrol attenuated all of these alterations (P<0.001). We conclude that resveratrol ameliorates glycerol-induced renal injury by suppressing the inflammatory process and by inhibiting lipid peroxidation.
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PMID:Effects of resveratrol on glycerol-induced renal injury. 1769 48

Bothrops insularis is a snake from Ilha da Queimada Grande, an island located about 20 miles away from the Southeastern coast of Brazil. Compared with other Brazilian species of Bothrops, the toxinology of B. insularis is still poorly understood, and so far, no fraction from this venom with amino acid oxidase activity had been isolated or its biological activity tested. We investigated the biochemical and biological effects of one l-amino acid oxidase enzyme isolated from B. insularis snake venom (BiLAO), which was purified using HPLC and sequence grade. We also evaluated the renal effects induced by BiLAO. Chromatographic profile of B. insularis whole venom disclosed seven main fractions (I, II, III, IV, V, VI and VII) and the main LAO enzymatic activity was detected in fraction II. The group treated with BiLAO showed a decrease in perfusion pressure (C(120)=110.28+/-3.69; BiLAO(120)=82.2+/-5.6 mmHg*); renal vascular resistance (C(120)=5.48+/-0.53; BiLAO(120)=4.12+/-0.42 mmHg/mL/g/min*), urinary flow (C(120)=0.160+/-0.020; BiLAO(120)=0.064+/-0.012 mL/g/min*), glomerular filtration rate (C(120)=0.697+/-0.084; BiLAO(120)=0.176+/-0.017 mL/g/min*), sodium (C(120)=79.76+/-0.56; BiLAO(120)=65.39+/-6.19%*), potassium (C(120)=69.94+/-6.86; BiLAO(120)=60.26+/-2.24%*) and chloride tubular reabsortion (C(120)=78.53+/-2.33; BiLAO(120)=64.58+/-6.68%*). Acute tubular necrosis foci were observed in the group treated with the LAO fraction of the B. insularis snake venom. Some findings have the same morphological aspect of apoptosis, more evident cortically; otherwise, reversible degenerative phenomena represented by hydropic ballooning with extensive cytoplasmic vacuolization and discontinuity of the cell brush borders in the proximal tubular epithelium were observed; furthermore, necrotic detachment of these cells into the tubular lumina, and increased amount of protein deposits in the distal and proximal tubules were observed. In conclusion, the slowness of blood flow and of glomerular filtration resulted in more time for filtration and tubular reabsorption, with elevation of the total percentage of sodium and chlorine reabsorption. The maintenance of the decrease in glomerular filtration rate would determine the subsequent decreases, which were noticed in these parameters. The necrosis observed was the result of damage cell induced by l-amino acid oxidase isolated from B. insularis venom.
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PMID:Purification and biological effects of L-amino acid oxidase isolated from Bothrops insularis venom. 1798 39

Tumor necrosis factor-alpha (TNF-alpha) is a mediator of inflammation and has an important role in human and experimental renal diseases. Pentoxifylline (PTX) has been shown to inhibit cytokine synthesis, including TNF-alpha. The aim of the present study was to examine the effect of PTX on meglumine antimonate (Sb(V)) and antimony pentachloride (SbCl(5))-induced renal toxicity in rats. Sixty Wistar rats were divided into six groups according to the treatment employed over the period of 7 days: group I-saline (NaCl 0.9%); group II-PTX plus saline; group III-meglumine antimonate (Sb(V)) plus saline; group IV-meglumine antimonate (Sb(V)) plus PTX; group V-SbCl(5) plus saline; group VI-SbCl(5) with PTX. The animals' urinary concentration ability was evaluated before and after the end of the treatment. Urine and blood osmolality, sodium and creatinine concentration, and urine volume per minute (V) were determined. Creatinine clearance (CrCl), fractional sodium excretion (FE(Na)), and urine to plasma osmolality ratio (U/P osm) were calculated. TNF-alpha concentration in blood was assessed. On the seventh day, the animals were sacrificed and their kidneys were submitted to histological analysis. The meglumine antimonate (Sb(V))-treated animals showed an impaired renal capacity to concentrate urine, with low values of the ratio U/P osm, reduction in CrCl, and an increment in TNF-alpha serum levels. PTX associated with meglumine antimonate (Sb(V)) reduced TNF-alpha serum levels and was effective in preventing renal functional alterations. Rats treated with SbCl(5) showed functional and histopathologic alterations compatible with acute tubular necrosis, and treatment with PTX did not prevent SbCl(5)-induced nephrotoxicity. PTX was effective in preventing renal functional alterations induced by meglumine antimonate (Sb(V)) in rats.
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PMID:Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride. 1802 9

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

Contrast induced nephropathy (CIN) remains a common complication of coronary angiography. There is no specific treatment once contrast induced acute renal failure develops, and management must be as for any cause of acute tubular necrosis, with the focus on maintaining fluid and electrolyte balance. The best treatment of CIN is prevention. A variety of preventive measures including the administration of intravenous saline or possibly sodium bicarbonate and the antioxidant acetylcysteine may reduce the risk of CIN.
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PMID:The value of hydration and acetylcysteine in the prevention of contrast-induced nephropathy: a potentially catastrophic complication of the percutaneous coronary interventions. 1765 30

Numerous anatomical and functional changes occurring in the aging kidney lead to reduced glomerular filtration rate, lower renal blood flow and impaired renal autoregulation. The elderly are especially vulnerable to the development of renal dysfunction and in this population acute renal failure (ARF) is a common problem. ARF is often iatrogenic and multifactorial; common iatrogenic combinations include pre-existing renal dysfunction and exposure to nephrotoxins such as radiocontrast agents or aminoglycosides, use of NSAIDs in patients with congestive cardiac failure and use of ACE inhibitors and diuretics in patients with underlying atherosclerotic renal artery stenosis. The aetiology of ARF is classically grouped into three categories: prerenal, intrinsic and postrenal. Prerenal ARF is the second most common cause of ARF in the elderly, accounting for nearly one-third of all hospitalized cases. Common causes can be grouped into true volume depletion (e.g. decreased fluid intake), decreased effective blood volume (e.g. systemic vasodilation) and haemodynamic (e.g. renal artery stenosis, NSAID use). Acute tubular necrosis (ATN) is the most common cause of intrinsic ARF and is responsible for over 50% of ARF in hospitalized patients, and up to 76% of cases in patients in intensive care units. ATN usually occurs after an acute ischaemic or toxic event. The pathogenesis of ATN involves an interplay of processes that include endothelial injury, microvascular flow disruption, tubular hypoxia, dysfunction and apoptosis, tubular obstruction and trans-tubular back-leak. Vasculitis causing ARF should not be missed as this condition is potentially life threatening. The likelihood of a postrenal cause for ARF increases with age. Benign prostatic hypertrophy, prostatic carcinoma and pelvic malignancies are all important causes. Early identification of ARF secondary to obstruction with renal imaging is essential, and complete or partial renal recovery usually ensues following relief of the obstruction.A comprehensive medical and drug history and physical examination are all invaluable. Particular attention should be paid to the fluid status of the patient (skin turgor, jugular venous pressure, lying and standing blood pressure, urine output). Urinalysis should be performed to detect evidence of proteinuria and haematuria, which will aid diagnosis. Fractional excretion of sodium and urine osmolality may be measured but the widespread use of diuretics in the elderly gives rise to unreliable results. Renal imaging, usually ultrasound scanning, is routinely performed for assessment of renal size and to exclude urinary obstruction. In some cases, renal biopsy is necessary to provide specific diagnostic information. The general principles of managing ARF include treatment of life-threatening features such as shock, respiratory failure, hyperkalaemia, pulmonary oedema, metabolic acidosis and sepsis; stopping and avoiding administration of nephrotoxins; optimization of haemodynamic and fluid status; adjustment of drug dosage appropriate to glomerular filtration rate; early nutritional support; and early referral to nephrologists for diagnosis of ARF cause, timely initiation of dialysis and initiation of specific treatment. The treatment of prerenal and ATN ARF is largely supportive with little evidence of benefit from current pharmacological therapies. Despite advances in critical care medicine and renal replacement therapy, the mortality of ARF has not changed significantly over the last 40 years, with current mortality rates being up to 75%.
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PMID:Management of acute renal failure in the elderly patient: a clinician's guide. 1854 Jun 87

The generation of endogenous hydrogen sulfide may either limit or contribute to the degree of tissue injury caused by ischemia/reperfusion. A total of 74 male Wistar rats were used to investigate the effects of endogenous and exogenous hydrogen sulfide in renal ischemia/reperfusion. Administration of the irreversible cystathionine gamma-lyase (CSE) inhibitor, dL-propargylglycine, prevented the recovery of renal function after 45 min ischemia and 72 h reperfusion. The hydrogen sulfide donor sodium hydrosulfide attenuated the (renal, tubular, and glomerular) dysfunction and injury caused by 45 min ischemia and 6 h reperfusion. Western blot analysis of kidneys taken at 30 min reperfusion showed that sodium hydrosulfide significantly attenuated phosphorylation of mitogen-activated protein kinases (p-38, c-JUN N-terminal protein kinase 1/2, and extracellular signal-regulated kinase 1/2) and activation of nuclear factor-kappaB. At 6 h reperfusion, sodium hydrosulfide significantly attenuated the histological score for acute tubular necrosis, the activation of caspase-3 and Bid, the decline in the expression of anti-apoptotic Bcl-2, and the expression of nuclear factor-kappaB-dependent proteins (inducible nitric oxide synthase, cyclo-oxygenase-2, and intercellular adhesion molecule-1). These findings suggest that (1) the synthesis of endogenous hydrogen sulfide by CSE is essential to protect the kidney against ischemia/reperfusion injury and dysfunction and aids in the recovery of renal function following ischemia/reperfusion, (2) hydrogen sulfide generated by sodium hydrosulfide reduces ischemia/reperfusion injury and dysfunction, and morphological changes of the kidney, and (3) the observed protective effects of hydrogen sulfide are due to both anti-apoptotic and anti-inflammatory effects.
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PMID:Generation of endogenous hydrogen sulfide by cystathionine gamma-lyase limits renal ischemia/reperfusion injury and dysfunction. 1867 78

Relationship between cirrhosis and renal dysfunction is not yet fully understood. A model of cirrhosis with acute hepatic and renal damage (RF), produced by CCl4 in rats, with hemodynamic and renal functional alterations, similar to those observed in decompensated cirrhosis (DC) in man, was used to study chemical nephrotoxicity in animals. We performed in male Wistar rats hepatic and renal functional and hemodynamic studies in control, cirrhotic and decompensated cirrhotic (DC) groups. Cirrhosis was induced with carbon tetrachloride by chronic administration. Association between liver and renal functional alterations was detected in rats with decompensated cirrhosis, showing fall in mean arterial pressure and reduction of glomerular filtration rate and filtration fraction. Renal hemodynamics did not change in cirrhotic rats, similarly to what occurs in compensated cirrhotic patients. However, DC rats exhibited increased sodium, glucose and phosphate urinary excretions and decreased ATP in renal cortex. DC animals had severe hypoglycemia. There was an extensive liver fibrosis. Glomeruli had hypercellularity and tubules showed extensive vacuolization in cirrhotic and DC rats. The present study suggests that in this model, damage typical of acute tubular necrosis ensues in cirrhotic rats. We describe functional and morphological damage in liver and kidney in a model of cirrhosis that might predispose to the development of acute renal failure when an individual with hepatic damage is exposed in acute way to chemical toxicants.
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PMID:Acute renal failure induced by carbon tetrachloride in rats with hepatic cirrhosis. 1903 32

The preoperative evaluation of patients with renal disease does not begin with the anaesthesiologist's visit, but with the evaluation and care given by the primary physician. To decrease postoperative morbidity and mortality, an optimal preoperative preparation is essential. The kidney is highly sensitive to perioperative hypoperfusion. Basically the medullary oxygenation with its high rate of oxygen extraction (about 79% of the delivered oxygen) is vulnerable to hypoxia, which may lead to acute tubular necrosis. The main goal of perioperative care is to avoid hypoperfusion and therefore hypoxia of the kidney. A perioperative equalized intravascular fluid balance (normovolaemia) seems to be the most effective strategy to prevent postoperative renal dysfunction. On the other side, the anaesthesia management depends on the renal function. The dosage of anaesthetics must be adapted to an impaired renal capacity. Accurate assessment of the renal function relies on laboratory determinations. The most useful laboratory tests are those related to the glomerular filtration rate (GFR), which represents the renal function. The measurement of the creatinine clearance is the most precise method available for clinically assessing overall renal function (really GFR). Measurement of creatinine clearance by 24-hour urine collection is uncomfortable and highly error-prone. For the estimation of GFR, the use of the Cockroft-Gault or the MDRD (Modification of Diet in Renal Disease) formula is recommended. The renal impairment is grouped according to the glomerular function, estimated by the named formula. Other important parameters to estimate the effects of an advanced renal dysfunction are the haemoglobin and the serum concentration of potassium and sodium. If possible, elective operative interventions should be carried out during a stable phase of the disease. Appropriate treatment of concomitant symptoms, such as hypertonia, is essential and contributes to a reduction of post operative renal dysfunction. Timely consultation with the responsible anaesthesist can prevent unnecessary delay of the intervention.
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PMID:[The preanaesthetic care of patients with renal disorder]. 1956 50


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