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

Studies were undertaken to determine whether a hypotensive episode under variable conditions is capable of inducing experimental acute renal failure in rats. Animals were subjected to hypovolemic shock by withdrawing volumes of blood necessary to maintain a systolic pressure of 30-40 mm Hg for 105-110 min. The blood was then reinfused and the animal was allowed to recover for 48 h prior to sacrifice. In an attempt to increase the injury, a second group of animals was salt-depleted prior to injury, a third group was volume-depleted by being deprived of H2O for 72 h prior of injury, a fourth group received 7.5 mg/kg indomethacin 30 min prior to injury, and a fifth group had 30% of the blood which was removed to produce shock hemolyzed and returned following the injury. In all groups examined, light microscopy revealed a moderate to severe acute tubular necrosis localized mainly in the outer stripe of the outer zone as defined by Peter (1909). Tubular damage was confined to the medullary pars recta of the proximal tubule and only in the most severe cases did injury involve the cortical pars recta and pars convoluta. Casts were present in the distal tubules and collecting ducts. Despite these significant histologic alterations, BUN values from all experimental groups remained within control levels. These studies clearly show that extensive necrosis of the medullary pars recta can be dissociated from the development of acute renal failure.
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PMID:Hypovolemic models of acute tubular necrosis in the rat kidney. 41 58

Scanning (SEM) and transmission (TEM) electron microscopy were used to elucidate morphological changes associated with acute tubular necrosis induced by high doses of mercuric chloride. Marked morphological changes were demonstrated in proximal tubules with TEM at one hour and with both SEM and TEM at six hours. These changes appeared earlier than reported in previous studies using any dose. The scanning microscopic provided a three-dimensional view of proximal cells showing changes in early injury with subsequent separation of the injured cells from the remaining cells. Certain of these residual cells change into low-lying cells with reline the proximal tubule. Variability was seen in the number of residual cells. However, once cell injury was initiated, necrosis proceeded in a reproducible manner.
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PMID:Scanning and transmission electron microscopy of mercuric chloride-induced acute tubular necrosis in rat kidney. 80 31

Large doses of cephaloridine cause acute necrosis of the proximal renal tubule that can be prevented by probenecid and other organic anions. Although there is little or no net secretion of cephaloridine by the mammalian kidney, the degree of cephaloridine uptake by the cortex of the rabbit kidney is substantial; this uptake is also prevented by probenecid and other organic anions. Cortical concentrations of cephaloridine were measured in control and probenecid-treated animals of different mammalian species. Evidence of cephaloridine trnsport was found in the guinea pig and the rat as well as in the rabbit. The degree of reduction of cortex-to-serum ratios by probenecid (control cortex-to-serum minus probenecid-treated cortex-to-serum ratios) correlated with the sensitivity to the nephrotoxicity of the drug. This degree or reduction was greatest in the rabbit, intermediate in the guinea pig, and least in the rat. In addition, the newborn rabbit, which is more resistant to the toxicity of cephaloridine than the adult, also had significantly lower cortical concentrations of cephaloridine. Finally, the acute tubular necrosis produced by extremely large doses of cefazolin in the adult rabbit was prevented by probenecid. It was concluded (1) that the nephrotoxicity of cephaloridine is related to its renal cortical transport with high intracellular concentrations of drug; and (2) that this relationship between transport and toxicity exists for cefazolin as well, although the toxicity is of a different order of magnitude. The unusual mechanism of cephaloridine transport in the proximal tubule was contrasted with that of the other cephalosporins in an attempt to explain its greater degree of nephrotoxicity.
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PMID:Relationship between the transport and toxicity of cephalosporins in the kidney. 115 24

Both chromate and citrinin have been shown to produce acute renal damage. Although both substrates act on the proximal tubule in the rat, they affect different parts of that nephron segment. As with most nephrotoxicants, the mechanism(s) or subcellular target(s) for citrinin or chromate is unknown. The availability of methodology for isolation of functional membrane vesicles has afforded the opportunity to study the plasma membrane as a target for the effects of citrinin and chromate. Whether studied solely with in vitro conditions or after administration to the rat, chromate exhibited its primary action on the basolateral (BL) membrane vesicles. This was exhibited by a reduction in the p-aminohippurate (PAH) overshoot. At both 3 and 16 hr after treatment (40 mg/kg, sc) there was a significant, but relatively modest, effect on glucose transport by brush border (BB) vesicles. Citrinin, when studied in vitro, inhibited PAH transport (BL vesicles), but had only equivocal effects on BB glucose transport. However, after pretreatment of the rats with citrinin (60 mg/kg, ip), both BL and BB membrane vesicle function was reduced markedly at 3 hr. By 16 hr, an overshoot had returned for both transport substrates, although the glucose overshoot was still significantly below control. These data demonstrate that both citrinin and chromate alter proximal tubular cell membrane function and do so relatively early after administration to the rat. This effect suggests that alteration of membrane function by these nephrotoxicants is an early, if not initiating, event in the production of acute tubular necrosis.
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PMID:The effects of potassium chromate and citrinin on rat renal membrane transport. 188 11

The purpose of this study was to characterize the spectrum of renal lesions associated with plasma cell dyscrasias from a population of patients who had renal disease identified by kidney biopsy. Thirty-six patients (2.6% of 1361 kidney specimens examined over 6 years) had evidence of monotypical light chain with or without concomitant heavy chain deposition. A variety of lesions was found, including (a) AL-amyloid and glomerular nonamyloid light chain deposition manifesting as nodular, membranoproliferative, mesangioproliferative, and "minimal-change" glomerulopathies; (b) fibrillary glomerulopathy; (c) tubulointerstitial lesions (cast nephropathy, acute tubular necrosis, and tubulointerstitial nephritis); and (d) vascular (arterioles and small and medium-sized arteries) lesions. AL-amyloid was the most common renal lesion (39%), nonamyloid deposition occurred second most commonly (33%), and cast nephropathy ("myeloma kidney") was third most frequent (14%). Clinical and laboratory manifestations of a plasma cell dyscrasia were frequently subtle. Immunoelectrophoresis of both serum and urine did not demonstrate a monotypical light chain or immunoglobulin in almost 35% of this population. Thus, the correct diagnosis was not considered in the majority of these patients before biopsy. Progressive deterioration of renal function was common with all of the lesions, except for proximal tubule injury, which tended to improve over the period of study. Renal biopsy with careful examination for monotypical light chain with or without associated heavy chain deposition using immunofluorescence or immunoelectron microscopy was crucial in identifying and characterizing the varied lesions associated with lymphoplasmacytic disorders.
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PMID:Spectrum of glomerular and tubulointerstitial renal lesions associated with monotypical immunoglobulin light chain deposition. 190 26

Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not yet been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent) (15 mg/kg body weight). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of beta 2-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome platers and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chronic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced exposure may produce persistent renal injury. The absence of evidence of chromate-induced chronic renal disease cannot be interpreted as evidence of the absence of such injury. Rather, it must be recognized that no prospective cohort or case-control study of the delayed renal effects of low-level, long-term exposure to chromium has been published.
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PMID:Chromium-induced kidney disease. 193 54

Medullary tubules in renal biopsies from twelve patients suffering from ischemic acute tubular necrosis (ATN) and nine patients with allergic, drug-induced acute interstitial nephritis (AIN) were investigated by electron microscopy using quantitative and semiquantitative methods. For comparison, 12 biopsies from patients without renal disease or with minimal change nephropathy were studied. The mean scores for reduction of brush border and basolateral infoldings of the cell surface were significantly increased in the straight part of the proximal tubule and the thick ascending loop of Henle (straight part of the distal tubule) compared with medullary controls, and these changes were significantly greater than the scores for the corresponding convoluted tubules in the cortex. The numbers of missing tubular epithelial cells (indicating sites of cellular desquamation) were significantly increased in the thick ascending loop of Henle in ATN as well as in AIN and in the straight proximal tubule in ATN. This single cell lesion also occurred in the collecting duct. These findings are discussed in the light of recent experimental data indicating the importance of medullary tubules for the pathogenesis of ATN.
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PMID:Ultrastructure of medullary tubules in ischemic acute tubular necrosis and acute interstitial nephritis in man. 228 9

1-(2-Chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and chlorozotocin (CZ; 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose) are structurally related anticancer agents which differ by virtue of the increased water solubility, and comparatively low carbamylating activity, of CZ relative to MeCCNU. In the present study, a single sc injection of either of these chloroethylnitrosoureas was nephrotoxic to male Fischer 344 rats. However, at equimolar doses, CZ was shown to be a much more potent nephrotoxicant. A lethal 40-mg/kg dose of CZ (127 microM) initially resulted in acute tubular necrosis of the proximal tubules of the cortex, followed later by a necrosis of papillary collecting ducts. In contrast, lethal doses of MeCCNU (100-180 mg/kg; 400-730 microM) produced only minimal proximal tubule injury. A 250-mg/kg (1 mM) dose of MeCCNU resulted in massive papillary necrosis within 7 days, with only limited necrosis to the proximal tubules. Sublethal doses of either drug, resulted in a similar, chronic, progressive nephropathy which was delayed in onset and was characterized by polyuria, enzymuria, a decrease in urine concentrating ability, and in renal slice organic ion accumulation. Alterations in less sensitive indicators of renal toxicity (i.e., proteinuria, glucosuria, and elevated blood urea nitrogen) were observed no earlier than 3 to 7 days after administration of only the highest tested doses of CZ (40 mg/kg) or MeCCNU (250 mg/kg). At sublethal doses, administration of either drug resulted in karyomegaly to the collecting ducts in the renal medulla within 2 to 4 weeks. These studies demonstrate that carbamylation-mediated reactions may not be necessary for nephrotoxicity to develop following administration of this class of antitumor agent.
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PMID:Comparative nephrotoxicity of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and chlorozotocin: functional-structural correlations in the Fischer 344 rat. 293 79

Studies were undertaken to determine the long-term effects of the nephrotoxin, uranyl nitrate, on the function and structure of the rat kidney. Animals were injected with 10 mg/kg B.Wt. of uranyl nitrate and renal function studies were performed one, two, four and eight weeks after drug administration. Light microscopy and scanning and transmission electron microscopy were used to characterize the morphologic changes at each time interval. Glomerular filtration rate was significantly reduced (P less than 0.01) one week (0.18 +/- 0.06 ml/min/100 gm B.Wt.) and two weeks (0.54 +/- 0.09 ml/min/100 gm B.Wt.) after drug treatment compared to controls (1.01 +/- 0.4 ml/min/100 gm B.Wt.) and returned to normal values by four weeks. The fractional excretion of sodium was significantly increased (P less than 0.01) one week after uranyl nitrate treatment (2.45% +/- 0.82) compared to controls (0.29% +/- 0.11). No further differences in this parameter were noted after one week. At all time intervals studied the pars recta of the proximal tubule (S2 and S3 segments) was the most consistently damaged region of the nephron. Acute tubular necrosis and tubular regeneration of these segments were evident one and two weeks after drug administration. Many of the tubules were widely dilated and lined by low-lying squamous epithelial cells. By four weeks some of these pars recta segments could be classified as microcysts and this type of lesion persisted as long as eight weeks after treatment. Regeneration of most injured proximal tubules was complete by eight weeks. Atrophic proximal tubules, marked interstitial fibrosis and a mononuclear cell infiltration, consistent with a chronic type of injury, were noted at the later time intervals. These results suggest that uranyl nitrate induces a persistent injury to the kidneys of rats causing lesions as long as eight weeks after injection.
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PMID:The long-term effects of uranyl nitrate on the structure and function of the rat kidney. 619 Mar 5

During the past five years, much has been learned about the complex pathophysiology of acute renal failure. A number of mechanisms appear to be involved, including cell swelling, inhibition of prostaglandin synthesis, tubular obstruction, and disruption of the basement membrane of the proximal tubule. For patients at high risk of acute tubular necrosis, prophylaxis with mannitol or furosemide (Lasix) should be considered under certain circumstances. If this syndrome does occur, management should focus on maintenance of proper fluid and electrolyte levels and nutrition, which is facilitated by dialysis. The prognosis of acute tubular necrosis has changed little in the past ten years, and mortality remains high.
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PMID:Acute renal failure. 2. Pathophysiology, prevention, management, and prognosis. 714 81


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