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

Renal tubular function was evaluated in vitro by kidney slice uptakes of p-aminohippurate (PAH) and tetraethylammonium (TEA) at 24 and 48 h in water-drinking rats and at 24 h in chronic saline-loaded rats after induction of acute tubular necrosis (ATN) by HgCl2 and glycerol injection. Significant correlations between decrease tubular uptake of PAH and TEA and elevated serum creatinine levels were noted in both models of ATN in water- and saline-drinking rats. However, with the same degree of impairment of PAH and TEA uptakes the creatinine was significantly lower in saline-loaded rats than in water-drinking rats in both forms of ATN. The correlation between impaired tubular function and elevated creatinine suggests that tubular damage and glomerular filtration reduction might be pathophysiologically related in ATN.
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PMID:The role of tubular necrosis in the pathophysiology of acute renal failure. 94 Jun 26

We studied renal function, urinary enzymes, urinary sediment, and renal histopathology in Fischer 344 rats that were treated with one dose of mercuric chloride (HgCl2) alone, HgCl2 followed by gentamicin, gentamicin alone, or gentamicin, followed by HgCl2. HgCl2 was administered intraperitoneally at 1 mg/kg body weight. Gentamicin was injected subcutaneously at 40 mg/kg body weight. Renal function was assessed by creatinine clearance. Urinary sediment was examined using transmission electron microscopy; particular attention was given to the numbers by myeloid bodies in the urinary sediment. Renal tissue was assessed using light microscopy for acute tubular necrosis (ATN). In either HgCl2- or saline-treated rats urinary sediment showed no myeloid bodies, and renal morphology was essentially normal. The rats given HgCl2 48 h prior to initiation of gentamicin therapy showed significant decrease of myeloid bodies excretion. This was accompanied by significantly less impairment of renal function, mild renal lesion, and no necrotic tubule cells in urinary sediment. The rats treated with either gentamicin alone or gentamicin followed by HgCl2 developed significant impairment of renal function in association with marked elevation of the urinary enzymes, and variable extent of ATN. In both of these groups, urinary sediment showed a profusion of free myeloid bodies and many necrotic renal tubule cells. The urinary sediment findings, however, did not aid in distinguishing between these two treatment groups. From these data we conclude that (1) a tentative relationship exists between the concentration of the urinary myeloid bodies and severity of gentamicin nephrotoxicity; (2) prior treatment with compound(s) analogous to HgCl2 which could minimize urinary excretion of the myeloid bodies might be useful in the mitigation of gentamicin nephrotoxicity.
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PMID:An electron microscopy study of urinary sediment: relationship between myeloid body excretion and gentamicin nephrotoxicity in the rat. 178 Apr 94

The effect of streptozotocin-induced diabetes mellitus on two different models of acute tubular necrosis (ATN), was studied: (i) the nephrotoxic model of HgCl2-induced ATN and (ii) the ischemic model of renal artery clamping for 60 min. Induction of ATN with HgCl2 in normal rats decreased CrCl from 0.67 +/- 0.05 to 0.1 +/- 0.019 ml/min (P less than 0.001) after 24 hr, and it deteriorated further to 0.03 +/- 0.013 ml/min after 48 hr; whereas, in the diabetic rats, HgCl2 decreased CrCl from 0.98 +/- 0.11 only to 0.31 +/- 0.037 ml/min (P less than 0.0001), but CrCl recovered to 0.50 +/- 0.08 ml/min after 48 hr. Bilateral clamping of renal arteries for 60 min in control and diabetic rats extremely decreased CrCl in both groups. Twenty-four hours after clamping, two of nine rats from the diabetic group died, whereas none from the control group died. Forty-eight hours after clamping, all nine rats from the diabetic group died, whereas only two rats from the control group died, and in the four surviving rats CrCl recovered slightly. Our study shows that streptozotocin-induced diabetes could not confer a general protection against ATN. It was protective against a nephrotoxic insult but aggravated the ischemic insult. An attempt to reconcile these discrepant effects is made in the Discussion.
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PMID:Opposite effects of diabetes on nephrotoxic and ischemic acute tubular necrosis. 216 56

Inductively coupled implanted coils have been shown to provide up to a 10-fold increase in signal-to-noise ratio when compared to whole-body imaging of small animals. The current study was designed to extend the implanted coil imaging technique to a rodent model of renal pathology. Resonant radiofrequency (RF) coils were implanted around the left kidney of four rats and inductively coupled from within a birdcage body coil. All images were acquired at 2 T using a T1-weighted spin-echo sequence with TR = 500 ms and TE = 20 ms. In vivo MR microscopy with voxels of 117 x 117 x 2000 microns demonstrated cortex, inner and outer medulla, and major vascular structures on baseline images. Mercuric chloride-induced nephrotoxic acute tubular necrosis (ATN) diminished cortico-medullary contrast at 24 h after dosing with pathologic evaluation demonstrating nephrotoxic changes in the inner cortex. The kidney regained a baseline MR appearance 360 h after dosing and resolution of the damage was confirmed with histology. T1 data were gathered on excised kidneys as an adjunct to the images to help correlate the loss and return of cortico-medullary contrast with the pathology and pathophysiology of nephrotoxic ATN. With implanted RF coils we were able to demonstrate renal pathology and follow its subsequent resolution. Specifically, loss and return of cortico-medullary contrast as a result of nephrotoxic ATN were serially documented in four rats. Such serial in vivo studies performed on single animals should further the use of MR microscopy by minimizing the number of animals required for adequate biostatistics.
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PMID:Implanted coil MR microscopy of renal pathology. 273 88

Rats were injected intraperitoneally with HgCl2 at doses of 2.5, 5, 7.5, and 10 mumol of Hg/kg. Urine was collected over a 24-hr period. At this time, plasma samples were taken and kidney damage was assessed by histological examination. Urinary gamma-glutamyltransferase levels were significantly elevated at Hg2+ doses of 7.5 and 10 mumol/kg, consistent with the detection of acute tubular necrosis by light microscopy. Resonances for a large number of low molecular weight metabolites were assigned in high resolution 1H NMR spectra of rat urine. Spectra from small volumes of urine (about 0.5 ml) were obtained in less than 5 min with no pretreatment. Significant Hg2+ dose-related decreases in the excretion of creatinine and citrate and increases of glucose, glycine, alanine, alpha-ketoglutarate, succinate, and acetate were detected. Elevated levels of lactate and creatinine in plasma of rats receiving the two highest doses were found by 1H NMR. There was a good correspondence between the histopathology, enzyme excretion, and 1H NMR urinary metabolite fingerprints in the assessment of Hg2+-induced renal damage. 1H NMR provided a sensitive measure of mercury-induced nephrotoxic lesions, and information on the molecular basis of mercury cytotoxicity was derived from the abnormal patterns of metabolite excretion. These suggested that primary metabolic effects of mercury were upon mitochondrial metabolism, in particular inhibition of certain citric acid cycle enzymes leading to decreased utilization of alpha-ketoglutarate and succinate by the renal tubular cells. The decrease in urinary citrate associated with Hg2+ dosing was attributed to intracellular, tubular acidosis with concomitant enhanced citrate reabsorption. The acidosis was assumed to arise from a combination of the inhibition of tubular carbonic anhydrase and a mild metabolic lactic acidosis due to increased activity of anaerobic pathways in the kidney. The possible extension of the 1H NMR techniques to the investigation of the nephrotoxic potential of other compounds and drugs is discussed.
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PMID:Proton NMR spectra of urine as indicators of renal damage. Mercury-induced nephrotoxicity in rats. 286 May 59

Sequential fast magnetic resonance (MR) images (repetition time = 33 ms, echo time = 7 ms, alpha = 22 degrees, one image every 12 s) were acquired using gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) (10 or 100 mumol/kg) to study perfusion and concentrating ability in normal rabbit kidneys and in kidneys with HgCl2-induced acute tubular necrosis (ATN). In normal rabbits receiving 100 mumol Gd-DTPA/kg a concentric region of decreased MR signal was observed. In sequential images the dark ring pattern migrated centripetally through the kidney moving from the corticomedullary junction to the inner medulla. The decrease in MR signal intensity occurred as a consequence of T2 relaxation (magnetic susceptibility) due to high concentration of Gd-DTPA within the tubules. This suggests that the dark ring pattern may serve as a qualitative feature indicative of the ability of the kidneys to concentrate. With the onset of HgCl2-induced ATN the pattern of enhancement due to Gd-DTPA administration changed markedly. Although the kidneys with ATN did continue to be perfused, the concentric dark ring pattern seen in normal kidneys receiving 100 mumol Gd-DTPA/kg was not observed. These results suggest that Gd-DTPA and fast imaging MR may provide a method of assessing perfusion and concentrating ability within the healthy or diseased kidney.
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PMID:Acute tubular necrosis: use of gadolinium-DTPA and fast MR imaging to evaluate renal function in the rabbit. 357 94

The cellular distribution of 65 and 70 kD heat shock proteins (HSPs) was studied in the normal rat kidney and after acute tubular necrosis (ATN) induced by inorganic mercury (HgCl2). In the normal kidney the 65 kD HSP was found in the cytoplasm of podocytes and proximal convoluted tubules, whereas the 70 kD HSP was located in nuclei and cytoplasm of podocytes, cortical convoluted, and collecting tubules. The distribution of both HSPs along ATN changed as a function of time. In the early phase, before evidence of histological damage, both HSPs were found in the pielocaly ceal epithelium and medullary collecting tubules. During the necrotic phase, HSPs coexisted with sites of severe damage (i.e. cortical tubules). With immunoelectron microscopy damaged cells showed an abundance of 65 kD HSP-I in mitochondria, as well as in chromatin and nucleoli, while 70 kD HSP-I was overexpressed in the cytoplasm, mito chondria, lysosomes, cytoskeleton, chromatin, and nucleoli, and coincided with urinary excretion of HSPs. In the postregenerative phase, the distribution of HSPs was similar to that found in the normal kidney. HSPs of 65 and 70 kD were encountered constitutionally and their immunolabeling is correlated with the magnitude of cell injury.
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PMID:Histological and subcellular distribution of 65 and 70 kD heat shock proteins in experimental nephrotoxic injury. 887 Oct 90

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

To examine the mechanisms involved in the progression of mercury chloride (HgCl2)-induced acute tubular necrosis (ATN), we investigated the histopathological changes and the expression of inducible nitric oxide synthase (iNOS) mRNA and protein in renal cortices of rats at 20 hours after exposure to HgCl2. The expression of iNOS mRNA was significantly augmented in renal cortices of rats with HgCl2-induced acute renal failure (ARF). Likewise, the induction of iNOS protein was observed in damaged proximal tubule epithelial cells of rats with HgCl2-induced ARF. Pretreatment of rats with iNOS inhibitor aminoguanidine, however, suppressed the development of proximal tubule epithelial cell injury and prevented an increase in blood urea nitrogen and serum creatinine as well as resulting in a marked fall in iNOS mRNA and protein in rats with HgCl2-induced ARF. These observations indicate that the induction of iNOS may play a role in the progression of HgCl2-induced ATN through the exacerbation of proximal tubule epithelial cell damage.
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PMID:Inducible nitric oxide synthase expression in mercury chloride-induced acute tubular necrosis. 981 Jan 45

S-(1,2-Dichlorovinyl)-L-cysteine (DCVC), a model nephrotoxicant in mice, causes acute tubular necrosis and death at high doses. Our earlier studies revealed that renal tissue repair was critical for survival in mice with DCVC nephrotoxicity. The objective of this study was to investigate if increasing renal tissue repair could protect mice from the lethal outcome of DCVC. Male Swiss Webster (SW) mice were administered a low dose of DCVC (15 mg/kg, ip) 72 h before injection of a normally lethal dose of DCVC (75 mg/kg, ip); this resulted in 100% protection against the lethal effect of DCVC. Because DCVC caused approximately two fold decrease in cytosolic and mitochondrial beta-lyase activity, the possibility that DCVC protection may be caused by decreased bioactivation was examined. Mercuric chloride (HgCl2, 6 mg/kg), a nephrotoxicant with no effect on beta-lyase activity, was administered 96 h before a lethal dose of DCVC. This also resulted in 100% protection from the lethal effect of DCVC. In both studies total glutathione was unchanged at any time after the lethal dose of DCVC was administered, obviating the role of glutathione in protection. In both cases the augmented and sustained tissue repair induced by priming dose and documented by 3H-thymidine pulse labeling and immunocytochemistry for proliferating cell nuclear antigen resulted in 100% survival in spite of the extensive renal injury. These findings suggest that stimulation of renal tubular repair by the priming dose, through augmented cell division, and the resistance of new cells to mechanisms of progression of injury, underlies auto- and heteroprotection against DCVC. The molecular mechanisms may have potential application in pharmacotherapeutic intervention for treatment of acute renal failure.
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PMID:Role of tissue repair in survival from s-(1,2-dichlorovinyl)-L-cysteine-induced acute renal tubular necrosis in the mouse. 1273 Jun 12


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