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)

We have previously shown that the rat with experimental diabetes (DM) of 4-6 months' duration exhibits complete functional and morphologic protection against gentamicin-induced acute renal failure. To assess the role of the duration of the diabetic state per se on the resistance to gentamicin, female Sprague-Dawley rats with diabetes of short (5 days, n = 7), intermediate (5 weeks, n = 5) and long duration (5 months, n = 7) were studied. Diabetes was induced by streptozotocin, 50-65 mg/kg b.w. i.v. Controls were identically treated sex- and age matched nondiabetic rats. The animals were kept in individual metabolic cages for 2 weeks and all received gentamicin 40 mg/kg/day for 9 days. Sham animals (DM and control) received Ringer's solution in place of gentamicin. Prior to gentamicin, plasma glucose levels and creatinine clearances (Ccr) were higher in the DM long duration group (619 +/- 25 (SE) mg/dl; 2.6 +/- 0.2 ml/min, respectively) than in the DM short (514 +/- 24; 2.0 +/- 0.1) and DM intermediate duration (442 +/- 30; 2.1 +/- 0.1) groups, while urine volume and glycosuria were similar. Following gentamicin the three control groups developed acute renal failure (maximal decrease in Ccr of 60 +/- 7, 72 +/- 9 and 71 +/- 7%, respectively; p less than 0.01 to less than 0.001), lysozymuria and acute tubular necrosis. There were no significant differences in the degree of renal impairment observed among the three control groups. In marked contrast, in the three DM groups these changes were absent and the renal cortical gentamicin content was lower than that of the control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of duration of diabetes on the protection observed in the diabetic rat against gentamicin-induced acute renal failure. 672 8

The capacity of exogenous amino acids to alter renal protein metabolism was studied during renal regeneration after mercuric chloride-induced acute tubular necrosis in the rat. In regenerating cortical tissue, the free leucine concentration was 17% lower than normal, and was decreased further after glucose infusion. The concentration was raised above normal by amino acid infusion thereby ameliorating the deficit of this amino acid. Synthesis and degradation of rapidly-turning over proteins in renal cortical cells was examined in vitro. Renal protein synthesis in cortical slices was assessed by measurements of tissue leucine specific radioactivity and cycloheximide-inhibitable [14C]leucine incorporation into protein. Protein synthesis in regenerating tissue was 52% higher than normal and was not increased further by glucose infusion. In contrast, amino acid infusion increased the rate 47% above that observed after an isocaloric glucose infusion, thereby demonstrating that amino acid enhancement of protein synthesis is superimposed upon the increased synthetic rate observed during renal regeneration. Renal protein degradation remained at the normal rate after amino acid infusion, but was increased in regenerating tissue and after glucose infusion. These results indicate that infused amino acids act on the kidney to enhance protein synthesis and reduce protein degradation in regenerating renal cells after acute tubular necrosis.
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PMID:Amino acid administration enhances renal protein metabolism after acute tubular necrosis. 684 54

Groups of ten male rats were treated with a high challenge dose of cephaloridine (CPH, 3750 mg kg-1), with methylprednisolone (MP, 100 mg kg-1) or with cephaloridine and methylprednisolone (CPH + MP) by single subcutaneous injection. A control group received the injection vehicles only. Urine was collected from all animals daily over 18-h collection periods, up to 96 h after treatment. Blood was collected at 24, 48, 72 and 96 h after treatment. At necropsy, kidneys were weighed, processed and examined histopathologically. Results show that methylprednisolone significantly ameliorated the nephrotoxicity of the challenge dose of cephaloridine. CPH-only treated rats had severe toxic nephrosis characterised by acute tubular necrosis, and elevated blood urea and creatinine. By contrast, the majority of CPH + MP treated rats had only a slight or moderate toxic nephrosis, and had lower blood urea and creatinine levels compared with rats treated with CPH only, indicating preservation of kidney function. Interestingly, rats treated with CPH + MP had higher urinary enzymes (alkaline phosphatase, lactate dehydrogenase, gamma glutamyltransferase and N-acetyl-beta-glucosaminidase) as well as protein and glucose, compared with rats treated with CPH only. This is taken to indicate that rats treated with CPH only had such marked kidney damage and necrosis that the population of cells able to produce these marker enzymes was significantly and rapidly depleted, but the protection afforded by methylprednisolone allowed CPH + MP treated rats to sustain urinary enzyme output. Effects on urinary glucose and other parameters such as body weight and kidney weight demonstrate interactions between glucocorticoid pharmacology and cephaloridine nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucocorticoid amelioration of nephrotoxicity: a study of cephaloridine-methylprednisolone interaction in the rat. 757 15

The vascular endothelium is an important mediator of vascular tone, angiogenesis, inflammatory-immune reactions, vascular permeability, and hemostasis. Thus, it plays an important role in the pathogenesis of numerous critical care processes, including septic shock, myocardial infarction, the adult respiratory distress syndrome, and acute tubular necrosis. Endothelial functions may be altered by changes in the local cellular environment, particularly changes in PO2. The ability of endothelial cells (EC) to not only sense, but also to adapt to, acute and chronic changes in PO2 is critical to maintaining endothelial metabolic functions and, in turn, to maintaining homeostasis, particularly in the critical care setting. Recent studies have shown that the EC is one of the more hypoxia-tolerant mammalian cell types; however, the mechanisms by which ECs respond and adapt to hypoxia are unknown. Our laboratory has shown that cultured ECs exposed to hypoxia upregulate a set of stress proteins, termed hypoxia-associated proteins (HAPs), that are distinct from the classically described stress proteins induced by heat shock (heat-shock proteins) or glucose deprivation (glucose-regulated proteins). We have recently identified one of these proteins as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Further studies have shown that GAPDH expression is regulated by hypoxia, primarily at the transcriptional level. Subcellular fractionation of hypoxic EC has shown that GAPDH is upregulated in the cytoplasmic fraction as would be expected with a glycolytic enzyme; however, a protein corresponding to GAPDH is also upregulated in the nuclear fraction. This suggests that the upregulation of GAPDH in EC during hypoxia is related to the potential nonglycolytic functions of this enzyme. Furthermore, the upregulation of GAPDH and the other HAPs (that have yet to be identified) may be related to the relative hypoxia tolerance of EC.
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PMID:Hypoxia-associated proteins. 758 62

Continuous peritoneal dialysis (CPD) was performed in 13 children with acute renal failure (ARF) in our intensive care units (ICU). The median age was 6 months (range 3 days to 77 months). Sixty-nine percent of the patients (9/13) were below the age of 12 months. CPD was performed for a median duration of 5 days (range 1-35 days). In 62% of the patients (8/13), the cause of ARF was acute tubular necrosis (ATN) due to cardiac surgery. The outcome of CPD regarding total survival was 54% (7/13). A high mortality was registered (83% of the deaths [5/6]) within the first year of life, which suggests a worse prognosis if ARF occurs at this age. Half of the total deaths (3/6) were among the cardiac surgery patients. Peritoneal equilibration tests (PET) were performed utilizing measurement of urea and glucose transport through the peritoneal membrane at short intervals during a period of 45-60 min from the start of treatment. Short dwell times of 5-20 min were found to be sufficient for adequate uremic control until a satisfactory daily urine production was noted. CPD is a useful and simple treatment modality for ARF in critically ill ICU children. Equilibration tests are useful and should be considered for optimization of CPD treatment in critically ill children with ARF in order to achieve the goal of controlling uremia and fluid overload, and giving nutritional support.
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PMID:Continuous peritoneal dialysis in children with acute renal failure. 799 47

Rats with untreated diabetes mellitus are protected from gentamicin-induced nephrotoxicity. In order to evaluate the role of hyperglycemia, glycosuria, and polyuria in this phenomenon, miniosmotic pumps filled with insulin were implanted for 15 days in seven female Sprague-Dawley rats with streptozotocin-induced diabetes mellitus. Plasma glucose levels were successfully maintained under 126 mg/dl. To serve as the control group, eight age-matched diabetic (plasma glucose > 400 mg/dl) rats had miniosmotic pumps placed delivering only Ringer's solution. Six days after placement of the pumps, gentamicin (40 mg/Kg/day) was administered to all animals for 9 days. The insulin-treated diabetic rats exhibited clear signs of nephrotoxicity by Day 6 of gentamicin, whereas the diabetic control group remained free from any functional or morphological evidence of proximal tubular damage throughout the 9 days of the aminoglycoside administration. At the end of the experiment, the creatinine clearance in the insulin-treated diabetic group was 45% lower than in the untreated diabetic group (P < 0.005). In addition, there was a rise in plasma creatinine (P < 0.02), muramidase appeared in the urine, and mild patchy acute tubular necrosis of the renal cortex was observed by light microscopic examination. The insulin-treated group also accumulated more gentamicin in the renal cortex than the untreated animals (P < 0.005). It is concluded that protection against the nephrotoxic effects of gentamicin is a feature of untreated experimental diabetes mellitus in the rat and that correction of the hyperglycemic state with insulin reverses this resistance.
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PMID:Insulin reverses the protection given by diabetes against gentamicin nephrotoxicity in the rat. 807 55

Nuclear medicine procedures have special indications in the follow-up of transplanted patients: In case of renal transplantation perfusion, function (glomerular filtration) and urinary flow measured by bolus application of 99mTc-DTPA is an important tool to detect and monitor acute tubular necrosis, rejection, urinary leakage, obstruction or vascular complications. This method is used for pancreatic grafts, too. To exclude rejection in case of heart transplantation more than one year after operation the antimyosin antibody scintigraphy is introduced avoiding biopsies. The radionuclide ventriculography is able to monitor heart function by determining the ejection fraction. Cholescintigraphy in liver transplants is sensitive to detect complications of bile flow. In case of an auxiliary liver transplantation a competition between two livers has been described. This method allows a distinction of functional performance of donor and recipient liver. The same problem is solved by ventilation-perfusion scan in lung transplants. Bone scintigraphy is of prognostic value for graft viability. Other radionuclide examinations have been developed to measure perfusion, glucose-, fat-metabolism to detect rejection episodes, abscesses or tumor recurrencies.
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PMID:[Functional scintigraphy in the follow-up of transplants]. 823 40

The culture of renal tubular cells from genetically modified animals opens the opportunity of biochemical, cell biology and physiological studies under strictly controlled conditions. Either primary cultures or cell lines can be used. Through two examples of primary cultures of proximal tubular cells obtained from knock-out mice, important information about the function of proteins were obtained. Mice lacking vimentin, an intermediate filament normally reexpressed in tubular cells during regeneration and culture, have a normal tubular function under basal conditions. Proximal cells grown from these animals exhibit a defect in sodium-glucose cotransport activity, most likely related to alterations in the dimer/monomer ratio of the transporter in the apical membranes. These alterations may be important in terms of tubular function during the recovery phase following acute tubular necrosis. The situation is strikingly different with regard to mice lacking HNF-1, a transactivator involved in the transcription of multiple genes. These animals suffer from severe Fanconi syndrome related to decreased expression of proximal transporters including isoforms of sodium-glucose (SGLT2) and sodium-phosphate (NPT1) cotransporters. Whereas transport defects are observed in isolated tubules, they are no longer apparent in cultured proximal cells because the expression of these isoforms is suppressed under culture conditions. These observations illustrate the interest and limits of the in vitro models for studying renal function in transgenic animals.
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PMID:Renal tubular cells cultured from genetically modified animals. 1055 38

This review evaluates the various causes and management of acute renal failure (ARF) in children. ARF is defined as an abrupt decline in the renal regulation of water, electrolytes and acid-base balance, and continues to be an important factor contributing to the morbidity and mortality of critically ill infants and children. The common causes of ARF in children include acute tubular necrosis secondary to various causes (including congestive heart failure and sepsis), haemolytic uremic syndrome, and glomerulonephritis and urinary tract obstruction. Ischaemia, toxins (including drugs) as well as primary parenchymal disease, have to be considered and ARF can also be a complication of systemic disease. The basic principles of management are avoidance of life-threatening complications, maintenance of fluid and electrolyte balance, and nutritional support. Only a few patients require specific management of the underlying disorder, although it is important to diagnose these conditions. Knowledge about the use of drugs for the prevention of ARF is scarce. Mannitol, low-dose dopamine, calcium channel antagonists, atrial natriuretic peptide and albumin have been evaluated and, where possible, meta-analyses are cited. Mannitol treatment appears to be warranted prophylactically after paediatric renal transplantation. Albumin infusion can reverse prerenal ARF in children with nephritic syndrome. For treatment of the complications of hyperkalaemia and volume overload, salbutamol, insulin and glucose infusion and diuretics such as furosemide and sodium bicarbonate, are discussed. All of the major dialysis modalities (peritoneal dialysis, haemodialysis and continuous haemofiltration) can be used to provide equivalent solute clearance and ultrafiltration. The indication for, and the choice of the modality depend on the patient requirements and on local resources, and should involve the care of a paediatric nephrologist. Peritoneal dialysis requires minimal equipment and infrastructure, is easy to perform and remains the favoured modality of renal replacement therapy in children. However, continuous haemofiltration is an excellent alternative to peritoneal dialysis in patients with ARF and severe fluid overload. Dialysis remains the most important tool to bridge the time needed for recovery of renal function. There is increasing evidence that more intense use of dialysis may improve the overall prognosis.
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PMID:Acute renal failure in children: aetiology and management. 1173 64

Vimentin, an intermediate filament protein mainly expressed in mesenchyma-derived cells, is reexpressed in renal tubular epithelial cells under many pathological conditions, characterized by intense cell proliferation. Whether vimentin reexpression is only a marker of cell dedifferentiation or is instrumental in the maintenance of cell structure and/or function is still unknown. Here, we used vimentin knockout mice (Vim(-/-)) and an experimental model of acute renal injury (30-min bilateral renal ischemia) to explore the role of vimentin. Bilateral renal ischemia induced an initial phase of acute tubular necrosis that did not require vimentin and was similar, in terms of morphological and functional changes, in Vim(+/+) and Vim(-/-) mice. However, vimentin was essential to favor Na-glucose cotransporter 1 localization to brush-border membranes and to restore Na-glucose cotransport activity in regenerating tubular cells. We show that the effect of vimentin inactivation is specific and results in persistent glucosuria. We propose that vimentin is part of a structural network that favors carrier localization to plasma membranes to restore transport activity in injured kidneys.
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PMID:Recovery of Na-glucose cotransport activity after renal ischemia is impaired in mice lacking vimentin. 1523 51


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