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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Shredded wheat moulded by an isolate of Penicillium aurantiogriseum elicited progressive histopathological changes at the rat renal cortico-medullary junction during 5 days of dosing, when incorporated into diet as a 20% component. The changes of acute tubular necrosis and regeneration were seen in the P3 segment of the nephron. In rats exposed to contaminated diet for 5 days the histopathological changes regressed in severity by about one-half within a further 4 days on normal diet and by 7 days the tubular epithelium was nearly normal. A partially purified fraction of an alcohol extract, selected by preparative high-voltage electrophoresis and anion exchange and notably rich in amino-compounds, was typically nephrotoxic when given in diet over 4 days. Acute marked tubular necrosis also occurred when the same fraction was given intraperitoneally over a similar period. The acute histological changes provide a rapid bioassay for this Penicillium nephrotoxicity and facilitate the search for the toxic metabolite(s). The cumulative expression of necrosis and repair over only a few days in tubular epithelium suggests that chronic exposure will elicit a more complex pathology which might serve as an experimental model for the idiopathic Balkan endemic nephropathy.
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PMID:Acute histopathological changes produced by Penicillium aurantiogriseum nephrotoxin in the rat. 188 65

Renal transplantation in infants has been associated with a high incidence of acute tubular necrosis and of renal artery thrombosis. Since 1978, 24 infants who received an adult kidney transplant at the University of Minnesota have had aggressive administration of intravenous colloids to increase the central venous pressure to 16-20 mm Hg before renal reperfusion. Acute tubular necrosis developed in only two infants, and there were no cases of renal artery thrombosis. Chest radiographic evidence of pulmonary edema was present in the recovery room in seven patients (29%) and within the first four postoperative days in five patients (21%). Yet, only two infants (8.3%) required postoperative mechanical ventilation beyond 24 h to manage fluid overload. With aggressive intravenous colloid administration, infants in renal failure can receive an adult kidney transplant with a low incidence of active tubular necrosis or renal artery thrombosis, but pulmonary edema may develop requiring ventilatory support.
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PMID:Anesthetic management of infants receiving an adult kidney transplant. 195 73

The macrophage cytokine tumor necrosis factor-alpha is released early in immune activation and may be detected in the peripheral circulation. This study has investigated the occurrence of plasma and urinary TNF in 30 renal allograft recipients. Although circulating TNF may be detected in 20% of pretransplant or normal control samples, levels were significantly elevated during 65% of allograft rejection episodes. Plasma TNF levels did not rise in graft failure due to acute tubular necrosis, but were always highly raised in systemic infection. In contrast, urinary TNF was only detected in association with acute rejection (49%) or tubular necrosis (14%), and no controls had detectable urinary TNF. These findings indicate that evaluation of circulating and excreted TNF may give further insight into the immunobiology of graft rejection.
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PMID:Evaluation of sequential plasma and urinary tumor necrosis factor alpha levels in renal allograft recipients. 204 98

Phosphorus magnetic resonance spectroscopy (31P MRS) was used to obtain in vivo spectra from rat kidneys undergoing acute tubular necrosis induced by a nephrotoxic dose of cephaloridine (CLD). Spectra were obtained 0, 24, and 48 h after injection of CLD (experimental group, n = 6) or saline vehicle (control group, n = 6). The nephrotoxicity of CLD was demonstrated by severely increased serum creatinine levels and the development of extensive proximal tubular necrosis in the CLD-injected rats, and the lack of such changes in the controls. 31P MRS showed an increase in the inorganic phosphate region signal (Pi, p = 0.004) and a decrease in the phosphodiester region signal (PDE, p = 0.01) in the experimental group by 48 h, whereas these parameters did not vary significantly in the control group during the experiment. Significant correlations were found between serum creatinine and the same two 31P MRS parameters. In summary, rat kidneys which have developed severe CLD-induced proximal tubular necrosis exhibit changes in the 31P spectrum 48 h after administration of the drug. The causes of these changes were not determined.
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PMID:A study of nephrotoxin-induced acute tubular necrosis with 31P magnetic resonance spectroscopy. 206 27

Dose-response and sequential studies of 2-bromoethylamine hydrobromide (BEA) nephrotoxicosis were carried out using Swiss ICR mice. For the dose-response study, 150 male mice, 30 per group, were injected intraperitoneally (ip) with 100, 200, 300, 400 or 500 mg BEA/kg and ten from each group were killed 1, 3 or 5 days after treatment. For the sequential study, 80 male mice were injected ip with 300 mg BEA/kg and ten were killed at 0.5, 1, 2, 3, 6, 12 or 18 hr, or 10 days after treatment. Control mice (10-15) in both studies were given 0.15 ml of 0.9% NaCl solution injected ip and were killed after 1, 3 or 5 days in the former study and after 18 hr of 10 days in the latter study. Mortality and the extent of the renal lesions were dose dependent. The percentage of mice with tubular necrosis varied from 0 in mice given 100 mg BEA/kg to 100 in mice given 400 mg BEA/kg. The percentage of mice with renal papillary necrosis was also dose dependent and varied from 0 in the 100 mg/kg group to 72 in the 400 mg/kg group. Degeneration of proximal tubules was detected 2 hr after treatment. Three hours after treatment, grossly, the renal cortex was diffusely pale and, microscopically, there was marked acute tubular necrosis. Epithelial cells lining the cortical tubules were regenerating 3 days after treatment. By 10 days after treatment cortical interstitial fibrosis was marked with many tubules lined by regenerating epithelium and many tubules were dilated. BEA-induced nephrotoxicosis in the mouse was primarily an acute cortical tubular necrosis.
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PMID:Acute cortical tubular necrosis in the Swiss ICR mouse induced by 2-bromoethylamine hydrobromide. 237 94

Foscarnet is a pyrophosphate analogue that has been successfully used in severe cytomegalovirus (CMV) infections. Little is known of the incidence and mechanisms of foscarnet-induced nephrotoxicity as most data comes from recipients of renal allografts or from patients with severe underlying disease or with other nephrotoxic drugs. We have retrospectively analyzed the evolution of renal function after 56 courses of foscarnet. In addition, we have prospectively studied the protective effects of hydration on foscarnet nephrotoxicity (2.5 liters of saline/day during the night before the foscarnet therapy and throughout the course of treatment). Foscarnet-induced acute renal failure was defined as a rise in serum creatinine of at least 25% from the basal value. An increase in serum creatinine occurred in 37 cases out of the 56 courses of foscarnet (66%). The mean serum creatinine prior to foscarnet was 80.5 +/- 3.3 mumol/l and the mean increase was 190 +/- 28.3 mumol/l (range 80-1,000). Peak serum creatinine was higher than 200 and 300 mumol/l in 16 and 13 patients, respectively. Kidney obtained at autopsy from a 30-year-old male with AIDS, CMV pneumonitis and acute renal failure secondary to foscarnet administration showed an extensive tubular necrosis. In the group which was prospectively hydrated only 1 patient had an acute renal failure. The mean serum creatinine at the peak (96 +/- 4 mumol/l) and at the end of the treatment (83 +/- 4 mumol/l) was significantly lower (p less than 0.05) than in non hydrated patients. In conclusion, foscarnet is a highly nephrotoxic drug which induces acute tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Foscarnet nephrotoxicity: mechanism, incidence and prevention. 255 31

Cisplatin (cis-diamminedichloroplatinum II) has emerged as an anticancer drug of considerable value for the chemotherapy of several human neoplasms. However, this agent often causes renal toxicity, which appears to be the dose-limiting untoward effect. The present animal study was undertaken to compare, with regard to kidney injury and renal tissue repair, cisplatin and carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II), a platinum derivative more recently introduced in clinics. Female Sprague-Dawley rats (four animals per group) were treated ip with cisplatin (4 or 8 mg/kg, delivered in four consecutive daily injections) or carboplatin (40 mg/kg given in one injection) and terminated 4, 7, and 21 days after drug administration. One hour prior to sacrifice, each animal received ip 200 microCi of [3H]thymidine for the measurement of DNA synthesis and cell proliferation (frequency of S-phase cells in renal tissue, determined by histoautoradiography). Cisplatin, particularly at 8 mg/kg, caused severe tubular injury (acute tubular necrosis) culminating in a long-lasting cystic tubular dilatation in the outer stripe of outer medulla. Tubular damage was followed by a sharp proliferative response, indicative of tubular regeneration. However, the proliferative activity was still above basal level at the end of the observation period, suggesting that the tissue repair process had not reached completeness 3 weeks after cisplatin administration. In contrast, carboplatin only induced focal tubular necrosis in proximal tubules. Distal and collecting tubules also showed ultrastructural evidence of hydropic degeneration after exposure to the latter drug. Renal tubular injury associated with carboplatin was followed by a mild proliferative response. From this study, we can infer that carboplatin is less nephrotoxic than cisplatin, but still causes histopathological alterations in renal tissue. Furthermore, the lesser nephrotoxicity of carboplatin has a primary origin and is not due to a more efficient tissue repair reaction.
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PMID:Tissue injury and repair in the rat kidney after exposure to cisplatin or carboplatin. 268 May 78

To examine the mechanisms of the nephrotoxic synergy of bacterial cell wall lipopolysaccharide (LPS) (or endotoxin) and the cephalosporin antibiotics, we have studied: 1) the effects on mean arterial blood pressure and the clearances of inulin, p-aminohippurate and cephaloridine (Cld) of a 12%-lethal dose of Escherichia coli 0111-B4 LPS (0.05 mg/kg b.wt.i.v.), with both low and high rates of saline infusion (0.1 ml/min vs. a 7.5-ml/kg load followed by 0.4 ml/min, respectively, in approximately 2-kg rabbits); 2) the separate and combined effects of LPS and saline infusion on the concentrations of Cld in renal cortex and serum; and 3) the separate and combined effects of LPS and saline infusion on the nephrotoxicity of Cld, quantified by acute tubular necrosis scoring and serum creatinine concentrations 48 hr after treatment with 90 mg/kg of Cld i.v. and by mitochondrial respiratory toxicity, depletion of reduced glutathione and production of lipid peroxidation products in renal cortex 1 hr after treatment with 90 to 360 mg/kg of Cld i.v. The following was found: 1) the increased saline infusion (saline) largely prevented an LPS-induced fall of inulin clearance and partially prevented a fall of blood pressure and p-aminohippurate and Cld clearance; 2) as a result, saline prevented slightly elevated late serum and cortical Cld concentrations in LPS-treated animals; 3) the tubular necrosis and elevation of serum creatinine caused by Cld alone was reduced slightly and that produced by the combination of LPS plus Cld was reduced greatly by saline; 4) the comparable mitochondrial respiratory toxicity found after Cld and LPS-plus-Cld was prevented by saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of the bacterial endotoxin-cephaloridine toxic synergy and the protective effects of saline infusion in the rabbit kidney. 334 35

A unique opportunity presented itself for a morphologic study of experimental unilateral acute renal failure (ARF) in male rats. The ARF had been induced in the rats by temporary occlusion (1h) of the left renal artery. Twenty-nine rats were divided into subsets as follows: 2-3 h, 24 h, 1 week, 2, 4, 8, and 12 weeks following release of occlusion. Microdissection showed a heterogeneous population of abnormally structured proximal tubules in which the regressive lesions of tubular necrosis were combined with the progressive reaction of repair. The lesions demonstrated are reminiscent of those which have been described in ARF in the human and in experimental animals. Many proximal tubules in the 2- to 3-hour subset presented 1-3 disruptive lesions (DLs) while greater numbers of proximal tubules from the 24-hour group presented 1-5 DLs. Many proximal tubules presented no DLs, but nearly all from the 24-hour subset (97-100%) displayed a squamate appearance which paralleled and was caused by acute tubular necrosis. At 1 week, a dilated pars recta was common, but by this time, the squamate pattern had disappeared. Many casts were present. At 2 weeks, many fewer casts were present in proximal tubules and none were seen at 4, 8 or 12 weeks. The nephrons, particularly the proximal tubules, presented a variety of structural alterations at 2, 4, 8 and 12 weeks. Changes of special interest include (1) the presence of swan-necks; (2) a distinctive squamate appearance of the proximal tubules in the animals killed at 24 h; (3) a spiral, curled appearance caused by differential hyperplasia in animals at 4, 8 and 12 weeks, and (4) a tendency for ischemic lesions to involve all layers of the renal cortex.
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PMID:Microdissection studies of the structural alterations induced in rat kidneys by experimental postischemic acute renal failure. 350 82

Pretreatment with the thromboxane synthase inhibitor OKY-046 but not the cyclo-oxygenase inhibitor ibuprofen protects against ischemia-induced acute tubular necrosis. However, ibuprofen together with the vasodilating agent prostaglandin E1 is protective. This suggests that a high prostaglandin to thromboxane ratio is the major factor operative in preventing tubular necrosis, the subject of this study. Rats that had unilateral nephrectomy (n = 60) with the exception of rats that had sham operations (n = 8) underwent 45 minutes of left renal pedicle clamping. Thirty minutes before the operation, the rats received either a saline solution or a thromboxane synthase inhibitor that was given intravenously. The inhibitors OKY-046 (2 milligrams per kilogram, n = 10), UK38485 (1 milligram per kilogram, n = 9) and U63357A (10 milligrams per kilogram, n = 10) were given as a single bolus while the inhibitor CGS13080 (0.1 milligram per kilogram, n = 9, and 1.0 milligram per kilogram, n = 7) was given by constant infusion and continued for 60 minutes after reperfusion. With saline solution therapy, five minutes after reperfusion, thromboxane B2 increased from 154 to 2,537 picograms per milliliter (p less than 0.00001) and 6-keto-prostaglandin F1 alpha increased from 51 to 266 picograms per milliliter (p less than 0.004). At 24 hours, the creatinine level increased from 0.5 to 2.8 milligrams per deciliter (p less than 0.00001). Only OKY-046 yielded a creatinine level at 24 hours of 1.2 milligrams per deciliter, a value lower than that for those in the saline solution control group (p less than 0.002). Furthermore, OKY-046 led to the highest prostaglandin to thromboxane ratio (p less than 0.035). The five other ratios which occurred after drug therapy were inversely related to the decrease in the creatinine value (r = -0.93, p less than 0.02). Histologically, OKY-046 was the only thromboxane synthase inhibitor to prevent acute tubular necrosis (p less than 0.05). Results show that a high prostaglandin to thromboxane ratio protects against acute tubular necrosis.
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PMID:A high plasma prostaglandin to thromboxane ratio protects against renal ischemia. 367 99


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