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

Nitrilotriacetate (NTA), an effective metal-chelating agent, has been used as a substitute for polyphosphates in household laundry detergents. Nephrotoxicity and renal tumorigenicity have been reported in experimental animals that received high doses of NTA po for 4 weeks to 2 years. Since NTA exists in water as a variety of NTA-metal complexes, it was important to investigate the biological effects of NTA in a complexed form. In this study, acute and subchronic toxicity of a ferric iron chelate of NTA (Fe-NTA) was investigated in rats. When Fe-NTA was given ip, acute tubular necrosis and renal failure occurred following a single injection of 15 mg iron/kg. Repeated injections of sublethal doses produced degeneration and necrosis of the proximal tubular epithelium and was associated with polyuria, glucosuria, aminoaciduria, and azotemia. After 9 days of treatment, regeneration of the tubular epithelium with atypical cells was observed. Except for a parenchymal iron deposit, no marked changes were observed in other organs. None of these effects were observed in animals given noncomplexed NTA. In conclusion, the toxicity observed following high doses of NTA given po may be the result of an absorbed metal-NTA chelate.
 ...
PMID:Acute renal failure and glucosuria induced by ferric nitrilotriacetate in rats. 397 99

Heme proteins transport oxygen and facilitate redox reactions. Heme, however, may be dangerous, especially when free in biologic systems. For example, iron released from hemoglobin-derived heme can catalyze oxidative injury to neuronal cell membranes and may be a factor in post-traumatic damage to the central nervous system. We have shown that heme catalyzes the oxidation of low density lipoproteins which can damage vascular endothelial cells. The endothelium is susceptible to damage by oxidants generated by activated phagocytes, and this has been invoked as an important mechanism in a number of pathologies including the Adulte Respiratory Distress Syndrome (ARDS), acute tubular necrosis, reperfusion injury and atherosclerosis. Because of its highly hydrophobic nature, heme readily intercalates into endothelial membranes and potentiates oxidant-mediated damage. This injury is dependent on the iron content of heme and is completely blocked when concomitant hemopexin is added. Ferrohemoglobin, when added to cultured endothelial cells, is without deleterious effects, but if oxidized to ferrihemoglobin (methemoglobin), it greatly amplifies oxidant damage. Methemoglobin, but not ferrohemoglobin, releases its hemes which can then be incorporated into endothelial cells. Cultured endothelial cells, when exposed to methemoglobin but not ferrohemoglobin, cytochrome c or metmyoglobin, potentiate this oxidant injury. Stabilization of the methemoglobin by cyanide, haptoglobin or capture of the heme by hemopexin abrogates this effect. Paradoxically, more prolonged exposure of endothelium to heme or methemoglobin renders them remarkably resistant to oxidant challenge. Endothelium defends itself from heme by induction of the heme degrading enzyme heme oxygenase and the concomitant production of large amounts of the iron binding protein ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heme and the vasculature: an oxidative hazard that induces antioxidant defenses in the endothelium. 808 43

Nephrotoxic lesions induced by cisplatin in rats are characterized by acute tubular necrosis in the outer stripe of the medulla. The purpose of this study was to examine the potential role of changes in metal binding proteins, and iron and copper content in urine and renal tissue in cisplatin-induced nephrotoxicity. Cisplatin was administered intravenously to groups of 20 rats at single doses of 0, 1, 2.5, and 5 mg/kg and rats were sacrificed at 1, 2, 3 and 6 days after treatment. Increased serum BUN and creatinine were observed at a dose of 5 mg/kg cisplatin on day 2 through day 6. Increased urinary copper excretion coincided with necrosis and increased BUN and creatinine on day 3 in the high-dose group. Evidence of renal injury was apparent histologically as karyomegaly at all dose levels as early as 48 hours after injection of cisplatin, prior to increases in urinary copper levels. No change in the distribution of metal binding proteins (transferrin, ferritin, ceruloplasmin, and metallothionein) evaluated by immunohistochemical staining, was seen. Based upon these results, it is unlikely that changes in metal excretion play a primary role in cisplatin-induced nephrotoxicity however, changes in nuclear function indicated by karyomegaly may be involved in early renal injury.
 ...
PMID:Assessment of the possible role of iron and copper in cisplatin-induced nephrotoxicity in the rat. 816 68

This report investigates the pathomechanism of acute renal failure caused by toxic acute tubular necrosis after treatment with the antiretroviral agent adefovir. A 38-year-old white homosexual man with human immunodeficiency virus infection and no history of opportunistic infections was maintained on highly active antiretroviral therapy (HAART), including hydroxyurea, stavudine, indinavir, ritonavir, and adefovir dipivoxil. Histologic examination of the renal biopsy showed severe acute tubular degenerative changes primarily affecting the proximal tubules. On ultrastructural examination, proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Functional histochemical stains for mitochondrial enzymes revealed focal tubular deficiency of cytochrome C oxidase (COX), a respiratory chain enzyme partially encoded by mitochondrial DNA (mtDNA), with preservation of succinate dehydrogenase, a respiratory chain enzyme entirely encoded by nuclear DNA (nDNA). Immunoreactivity for COX subunit I (encoded by mtDNA) was weak to undetectable in most tubular epithelial cells, although immunoreactivities for COX subunit IV and iron sulfur subunit of respiratory complex III (both encoded by nDNA) were well preserved in all renal tubular cells. Single-renal tubule polymerase chain reaction revealed marked reduction of mtDNA in COX-immunodeficient renal tubules. We conclude that adefovir-induced nephrotoxicity is mediated by depletion of mtDNA from proximal tubular cells through inhibition of mtDNA replication. This novel form of nephrotoxicity may serve as a prototype for other forms of renal toxicity caused by reverse transcriptase inhibitors.
 ...
PMID:Adefovir nephrotoxicity: possible role of mitochondrial DNA depletion. 1209 87

It was reported that reactive oxygen metabolites play an important role in the pathogenesis of several renal diseases including glomerulonephritis, ischemia and acute tubular necrosis. However, the effect of oxidants and protective effect of sex steroid hormones on Na+/glucose cotransporter of renal proximal tubular cells is not yet elucidated. In the present study, we examined the effect of sex steroid hormones against tert-butyl hydroperoxide (t-BHP)-induced alteration of Na+/glucose cotransporter activity in primary cultured rabbit renal proximal tubule cells (PTCs). t-BHP inhibited alpha-methyl-D-glucopyranoside (alpha-MG) uptake in a dose-dependent manner. t-BHP-induced inhibition of alpha-MG uptake was due not to Km but to the decrease of Vmax. 0.5 mM t-BHP-induced inhibition of alpha-MG uptake was significantly blocked by estradiol-17beta, but not by progesterone and testosterone. This protective effect was not blocked by estrogen receptor antagonist or transcription and translation inhibitor. In addition, 0.5 mM t-BHP increased [3H]-arachidonic acid (AA) release and Ca2+ uptake. These effects of t-BHP were also significantly blocked by estradiol-17beta, but not by progesterone and testosterone. Protective efficacy of estradiol-17beta on t-BHP-induced inhibition of alpha-MG uptake is exhibited between antioxidants and iron chelators. In conclusion, estradiol-17beta, but not progesterone and testosterone, partially prevented t-BHP-induced inhibition of alpha-MG uptake through its antioxidant activity dependent upon phenol structures and inhibition of AA release and Ca2+ influx.
 ...
PMID:Effects of sex hormones on Na+/glucose cotransporter of renal proximal tubular cells following oxidant injury. 1152 8

Melatonin, the pineal hormone with antioxidative properties was administered to rats with glycerol-induced myoglobinuric acute renal failure (Gly-ARF). This model is characterized by acute tubular necrosis mediated by heme-iron oxidative stress. Rats received melatonin (20 mg/kg) concomitant and 3 h after glycerol injection. Gly-ARF rats showed at 24 h a 78% reduction in glomerular filtration rate, whereas this decrement was significantly reduced to 35% in the melatonin treated Gly-ARF rats. Tubular function evaluated by tubular reabsorption of sodium and lithium was also preserved in melatonin treated rats. The histologic analysis revealed extensive cortical tubular necrosis that was significantly reduced by melatonin treatment. The renal concentration of malondialdehyde (MDA) was increased 6 h after glycerol injection in Gly-ARF and this elevation was prevented when melatonin was administered. Renal concentration of reduced glutathione (GSH) was decreased at 6 h in Gly-ARF and melatonin did not reverse this decrease. It was concluded that melatonin administration attenuated the renal injury in the glycerol model of acute renal failure and reduced kidney oxidative stress through a GSH-independent mechanism.
 ...
PMID:Effects of melatonin administration to rats with glycerol-induced acute renal failure. 1247 96

Hemoglobin and myoglobin heme pigments and iron have acute and chronic nephrotoxic effects, which are often associated with massive hemolysis and rhabdomyolysis. We report a patient with a myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria phenotype who developed an acute renal failure after a severe haemolytic crisis. There was not evidence of renal vascular pathology, urinary tract obstruction or prerenal factors. Renal biopsy showed features of acute tubular necrosis, with extended iron deposits in tubule cell cytoplasm and tubulo-interstitial fibrosis and atrophy. The patient was oliguric requiring hemodialisys during three weeks, recovering renal function on the fourth week after admission. This case underlines the nephrotoxic role of heme pigment and iron, and possible pathophysiologic mechanisms involved in acute and chronic toxicity of both agents are reviewed.
 ...
PMID:[Acute renal failure in a patient with myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria phenotype]. 1521 70

Magnetic resonance imaging (MRI) of normal and diseased kidneys shows great promise because of the combined value of anatomical and functional information provided, as well as of specific contrast patterns that can be observed non-invasively. Multicontrast MRI is able to show infiltrative kidney disorders. Diffusion-weighted imaging can assess alterations in renal function and can suggest obstruction or inflammation when present. Due to the low nephrotoxicity, contrast-enhanced MR studies using serial dynamic enhancement with non-specific gadolinium chelates are able to provide information on glomerular filtration. Furthermore, contrast agents such as ultrasmall particles of iron oxide, specific of inflammation, should be used in the near future to detect active from quiescent involvement, both in native kidneys and renal allografts. Early results should indicate that these compounds might differentiate acute tubular necrosis from other acute nephropathies, as well as active proliferative nephropathies from chronic ones. Ongoing studies will obviously demonstrate the value of the combination of these various MRI sequences in the diagnosis of acute renal failure and chronic kidney disease.
 ...
PMID:Magnetic resonance imaging in acute and chronic kidney diseases: present status. 1654 56

The purpose of this study was to evaluate the detection and characterization of macrophage infiltration in native and transplanted kidneys using ultrasmall superparamagnetic iron oxide particles (USPIO). Among 21 patients initially enrolled, 12 scheduled for renal biopsy for acute or rapidly progressive renal failure (n = 7) or renal graft rejection (n = 5) completed the study. Three magnetic resonance (MR) sessions were performed with a 1.5-T system, before, immediately after and 72 h after i.v. injection of USPIO at doses of 1.7-2.6 mg of iron/kg. Signal intensity change was evaluated visually and calculated based on a region of interest (ROI) positioned on the kidney compartments. Histological examination showed cortical macrophage infiltration in four patients (>5 macrophages/mm(2)), two in native kidneys (proliferative extracapillary glomerulonephritis) and two in transplants (acute rejection). These patients showed a 33 +/- 18% mean cortical signal loss on T2*-weighted images. In the remaining eight patients, with <5 macrophages/mm(2), there was no cortical signal loss. However, in three of these, presenting with ischemic acute tubular necrosis, a strong (42 +/- 18%) signal drop was found in the medulla exclusively. USPIO-enhanced MR imaging can demonstrate infiltration of the kidneys by macrophages both in native and transplanted kidneys and may help to differentiate between kidney diseases.
 ...
PMID:USPIO-enhanced MR imaging of macrophage infiltration in native and transplanted kidneys: initial results in humans. 1792 25

Marginal donors (advanced age, comorbidities, and so on) provide an increasing contribution to the kidneys used to alleviate the relative organ shortage. We describe the evaluation process and clinical outcome of two kidneys with hemosiderosis used as a double graft. The donor was a 59-year-old hypertensive man, known to have a mechanical mitral valve, who died from a cerebral hemorrhage, with a normal serum creatinine (SCr) and kidneys with normal appearances at sonography. A protocol donor biopsy showed a Karpinsky score of 5 for both kidneys. A double graft was therefore scheduled. The recipient was a 59-year-old man, on dialysis because of chronic glomerulonephritis. HLA match was incompatibility 4/6; immunosuppression was based on steroids, cyclosporine, and mycophenolate mofetil with basiliximab as induction therapy. The grafts showed delayed function with dialysis treatments performed from postoperative day (POD) 1. On POD 2, a magnetic resonance imaging (MRI) study showed the typical appearance of siderosis. Pearl's staining performed on a protocol biopsy confirmed the presence of widespread iron deposits. On POD 5, a recipient renal biopsy showed a superimposed severe acute tubular necrosis. Renal function recovered slowly; SCr at discharge on POD 22 was still 4.2 mg/dL. Two months later, the SCr was 2.2 mg/dL. A second MRI performed at 3 years and 6 months after transplantation confirmed a progressive removal of iron overload while the patient had stable renal function (glomerular filtration rate) of 33 mL/min and SCr: 2.3 mg/dL. We concluded that donors with hemosiderosis should be treated as marginal donors and may be grafted based on a pretransplant biopsy.
 ...
PMID:Donor affected by hemosiderosis: is kidney transplantation possible? A case report. 1867 62


1 2 Next >>