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)

The roles of growth factors in the pathogenesis of various forms of acute and chronic renal disease are largely putative. Nevertheless, there is a growing body of information that links specific growth factors to particular forms of renal injury. In all instances, it is supposed that such associations are not necessarily unique and that multiple cytokines probably interact to determine the pattern of injury or the regenerative response to such injury. Regeneration of tubular epithelium after acute tubular necrosis involves upregulation of the epidermal growth factor (EGF) receptor. Early studies of exogenously administered EGF indicate that the severity and duration of renal failure may be attenuated by this growth factor. Thus far, the observed responses have been limited and the role of EGF as a therapeutic agent requires more study. The mechanism of generation of tubulointerstitial injury in most forms of renal disease is difficult to understand. Early in vitro studies of growth factor production by tubular cells (in the absence of any infiltrating cells) indicate that platelet-derived growth factor produced by the medullary collecting duct is mitogenic for renal medullary fibroblasts, suggesting a paracrine growth system in this region of the kidney. Insulin-like growth factor I has also been shown to be produced by collecting duct cells. Its production is increased by EGF, and its association with certain forms of renal hypertrophy, i.e., diabetes and hypersomatotrophic states, implies its participation in the hypertrophic growth response. Platelet-derived growth factor is a potent mitogen for glomerular mesangial cells, and its production is regulated by a variety of cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evolving role of growth factors in the renal response to acute and chronic disease. 159 57

To further characterize changes in tubular Na-K-ATPase in acute tubular necrosis (ATN), segmental analysis was performed in rat nephrons. Na-K-ATPase was assayed in the following segments: proximal convolution (PC), proximal straight (PS), outer medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convolution (DC) and cortical collecting duct (CCD) in three groups of rats: 1.) intact; 2.) moderate non-oliguric ATN; and 3.) severe oliguric ATN. GFR and CNa/GFR X 100 were in group 1 0.80 +/- 0.05 ml/min and 0.68 +/- 0.06, in group 2 0.14 +/- 0.02 and 1.46 +/- 0.35, and in group 3 0.04 +/- 0.01 and 0.46 +/- 0.15, respectively. Na-K-ATPase in PC and PS were similar in all three groups. Na-K-ATPase levels were in MTAL: in group 1 37 +/- 2 X 10(-11) mol/mm/min, in group 2 20 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 24 +/- 2 X 10(-11), P less than 0.001 versus group 1. In CTAL Na-K-ATPase levels were: in group 1 40 +/- 2 X 10(-11), in group 2 33 +/- 1 X 10(-11), P less than 0.001 versus group 1, and in group 3 27 +/- 2 X 10(-11), P less than 0.001 versus groups 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced Na-K-ATPase in distal nephron in glycerol-induced acute tubular necrosis. 215 4

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

Nucleated nonsquamous cells in urine of patients with crescentic glomerulonephritis (CN), noncrescentic glomerulonephritis (NCN), acute tubular necrosis (ATN) and drug related acute interstitial nephritis (AIN) were identified using monoclonal antibodies and immunoperoxidase stain. Cell viability was determined by trypan blue permeability. CN was distinguishable from NCN by total cell numbers exceeding 30,000/ml (p less than 0.001) and counts of granulocytes exceeding 10,000/ml (p less than 0.05), monocytes exceeding 3,000/ml (p less than 0.001), T4 lymphocytes exceeding 1,500/ml (p less than 0.001), T8 lymphocytes exceeding 1,500/ml (p less than 0.001), glomerular epithelial cells exceeding 4,000/ml (p less than 0.001), proximal tubular cells exceeding 8,000/ml (p less than 0.001), loop of Henle cells exceeding 1,500/ml (p less than 0.01) and urothelial cells exceeding 1,500/ml (p less than 0.05). AIN was distinguishable from ATN by total cell numbers exceeding 75,000/ml (p less than 0.001) and counts of granulocytes exceeding 150,000/ml (p less than 0.001), monocytes exceeding 5000/ml (p less than 0.001), T4 lymphocytes exceeding 3,000/ml (p less than 0.01), T8 lymphocytes exceeding 2,500/ml (p less than 0.01) and cell viability exceeding 60% (p less than 0.05). Proximal tubular, loop of Henle, distal tubular/collecting duct and urothelial cells were present in high numbers in CN, ATN and AIN. CN can be distinguished from NCN, and ATN can be distinguished from AIN by identifying and quantifying the nucleated cells present in the urine.
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PMID:Immunoperoxidase identification of nucleated cells in urine in glomerular and acute tubular disorders. 266 90

Accurate identification of nucleated cells in urine can be difficult with conventional methods of microscopic urinalysis. Monoclonal antibodies were used with an immunoperoxidase technique to identify nucleated cells in urine. This new development in urinalysis is in its early stages, but it has helped to circumvent the difficulties associated with standard microscopy. The monoclonal antibody technique allowed for the identification of granulocytes, monocytes, lymphocytes, glomerular epithelial, proximal tubular, loop of Henle, distal tubule/collecting duct, and urothelial cells in urine, and by quantifying these cells it was possible to determine the urine cell profiles in various renal diseases as well as in allograft rejection and early post-transplant acute tubular necrosis in renal allograft recipients. The cell profiles are useful in aiding the diagnosis of these conditions.
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PMID:Monoclonal antibodies: use in urine sediment examination. 304 54

The physical properties and chemical composition of urine are highly variable and are determined in large measure by the quantity and the type of food consumed. The specific gravity is the ratio of the density to that of water, and it is dependent on the number and weight of solute particles and on the temperature of the sample. The weight of solute particles is constituted mainly of urea (73%), chloride (5.4%), sodium (5.1%), potassium (2.4%), phosphate (2.0%), uric acid (1.7%), and sulfate (1.3%). Nevertheless, urine osmolality depends only on the number of solute particles. The renal production of maximally concentrated urine and formation of dilute urine may be reduced to two basic elements: (1) generation and maintenance of a renal medullary solute concentration hypertonic to plasma and (2) a mechanism for osmotic equilibration between the inner medulla and the collecting duct fluid. The interaction of the renal medullary countercurrent system, circulating levels of antidiuretic hormone, and thirst regulates water metabolism. Renin, aldosterone, prostaglandins, and kinins also play a role. Clinical estimation of the concentrating and diluting capacity can be performed by relatively simple provocative tests. However, urinary specific gravity after taking no fluids for 12 h overnight should be 1.025 or more, so that the second urine in the morning is a useful sample for screening purposes. Many preservation procedures affect specific gravity measurements. The concentration of solids (or water) in urine can be measured by weighing, hydrometer, refractometry, surface tension, osmolality, a reagent strip, or oscillations of a capillary tube. These measurements are interrelated, not identical. Urinary density measurement is useful to assess the disorders of water balance and to discriminate between prerenal azotemia and acute tubular necrosis. The water balance regulates the serum sodium concentration, therefore disorders are revealed by hypo- and hypernatremia. The disturbances are due to renal and nonrenal diseases, mainly liver, cardiovascular, intestinal, endocrine, and iatrogenic. Fluid management is an important topic of intensive care medicine. Moreover, the usefulness of specific gravity measurement of urine lies in interpreting other findings of urinalysis, both chemical and microscopical.
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PMID:Relative density of urine: methods and clinical significance. 307 30

To evaluate possible causes of the diminished prostaglandin production in advanced hepatorenal syndrome, prostaglandin endoperoxide synthase and prostacyclin synthase were localized and semiquantitated by immunofluorescence in postmortem, biopsy and nephrectomy renal tissues. In normal kidneys, antiprostacyclin synthase serum caused intense staining in peritubular capillaries, in the adjacent renal interstitial cells and in glomerular mesangial regions. Antiprostaglandin endoperoxide synthase serum caused staining of collecting duct epithelial cells, cells of the thin ascending limb and possibly glomerular mesangial cells. Prostacyclin synthase-positive staining was graded 5+ (scale of 0+ to 5+) in all kidney samples. Medullary collecting tubule prostaglandin endoperoxide synthase-positive staining was graded 4+ or 5+ in kidney samples from patients with acute tubular necrosis or acute tubulointerstitial nephritis and from patients with liver failure without the hepatorenal syndrome. However, prostaglandin endoperoxide synthase-positive staining was markedly diminished or absent (average 1+) in patients with the hepatorenal syndrome. These data suggest that loss of the medullary prostaglandin endoperoxide synthase is the cause of diminished urinary prostaglandin E2 excretion in the hepatorenal syndrome.
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PMID:Immunohistochemical distribution of renal prostaglandin endoperoxide synthase and prostacyclin synthase: diminished endoperoxide synthase in the hepatorenal syndrome. 311 64

Many renal diseases involving the tubular epithelium appear to preferentially affect certain nephron segments. While major portions of the nephron, such as proximal and distal convoluted tubules and collecting ducts, can be identified in the normal kidney, the distinction of diseased nephron segments can be difficult in tissue sections. Thus, to identify which nephron segments are involved in pathologic changes is usually impossible by routine histologic examination alone. Recently antibody and lectin probes that react with specific nephron segment-specific epitopes and carbohydrates, respectively, have become available. Some of these antibodies and lectins can be used on formalin-fixed, paraffin-embedded, archival tissues. Because renal tubules appear to retain their nephron segment-specific epitopes and glycoprotein moieties under most pathologic conditions, these nephron segment-specific tubular epithelial markers provide a method to study renal diseases involving the tubular system also in archival material. Such nephron segment-specific tubular epithelial markers are: the lectins, Tetragonolobus purpuras and Phaseolus vulgaris erythroagglutinin (proximal tubular markers); antibodies to low-molecular-weight cytokeratin (AE1/AE3); epithelial membrane antigen and the lectin Arachis hypogaea (distal nephron [distal convoluted tubule and collecting duct] markers); and antibodies to Tamm-Horsfall protein (labeling the thick ascending limb of Henle). We review the application of these and other renal tubular epithelial markers in the normal kidney and in various renal diseases including cystic disease of the kidney, interstitial nephritis, tubular atrophy, acute tubular necrosis, myeloma cast nephropathy, and renal tumors.
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PMID:Immunohistochemical and lectin dissection of the human nephron in health and disease. 825 Jun 94

Cytodiagnostic urinalysis was tested to determine its utility in the differential diagnosis of acute renal failure (ARF). Fifty-one patients with acute renal failure were included and evaluated clinically with regard to the etiology of the renal failure, whether underlying chronic renal failure was present, and if dialysis was required. Urine specimens were macroscopically examined and subjected to a multiparameter reagent-strip analysis. Papanicolaou stain was done on cytocentrifuge preparations and the number of blood cells, renal cells, and casts examined in a standardized fashion. The results showed that the 34 patients with acute tubular necrosis (ATN) of either ischemic or toxic origin had a higher number of collecting duct cells, and a higher total number of casts than the 17 non-ATN patients. Twelve patients requiring dialysis had a higher number of different types of casts (granular, waxy, leukocytic, broad casts) as well as more renal cells (mainly necrotic) than the 39 patients who did not require dialysis. A significant positive correlation was found between the magnitude of rise of serum creatinine and a number of cytodiagnostic parameters. We conclude that cytodiagnostic urinalysis may be valuable in addition to other tests in the evaluation of patients with acute renal failure.
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PMID:Cytodiagnostic urinalysis is very useful in the differential diagnosis of acute renal failure and can predict the severity. 877 Dec 45

Osmotic diuretics are used successfully to alleviate acute tubular necrosis (ATN) produced by chemotherapeutic agents and aminoglycoside antibiotics. The beneficial action of these agents likely involves rapid elimination of the nephrotoxic agents from the kidney by promoting diuresis. Adenosine A1 receptor (A1AR) subtype present on renal proximal tubular epithelial and cortical collecting duct cells mediates the antidiuretic and cytoprotective actions of adenosine. These receptors are induced by activation of nuclear factor (NF)-kappaB, a transcription factor reported to mediate hyperosmotic stress-induced cytoprotection in renal medullary cells. In this study, we tested the hypothesis that induction of the A1AR in renal proximal tubular cells by NF-kappaB contributes to the cytoprotection afforded by osmotic diuretics. Exposure of porcine renal proximal tubular epithelial (LLC-PK1) cells to mannitol or NaCl produced a significant increase in A1AR. This increase was preceded by adenosine release and NF-kappaB activation. Expression of an IkappaB-alpha mutant, which acts as a superrepressor of NF-kappaB, abrogated the increase in A1AR. Cells exposed to mannitol demonstrated increased reactive oxygen species (ROS) generation, which was attenuated by inhibiting xanthine oxidase with allopurinol. Allopurinol attenuated both the increase in A1AR expression and NF-kappaB activation produced by osmotic diuretics, indicating a role of adenosine metabolites in these processes. Treatment of LLC-PK1 cells with cisplatin (8 microm) resulted in apoptosis, which was attenuated by mannitol but exacerbated by selective A1AR blockade. Administration of mannitol to mice increases A1AR expression and activation of NF-kappaB in renal cortical sections. Taken together, these data provide novel mechanisms of nephroprotection by osmotic diuretics, involving both activation and induction of the A1AR, the latter mediated through activation of a xanthine oxidase pathway leading to ROS generation and promoting activation of NF-kappaB.
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PMID:Osmotic diuretics induce adenosine A1 receptor expression and protect renal proximal tubular epithelial cells against cisplatin-mediated apoptosis. 1527 17


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