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)

A sandwich ELISA assay has been formatted from two commercially available murine monoclonal antibodies, URO-4 and URO-4a, directed against a 120,000 dalton glycoprotein, the adenosine deaminase binding protein (ABP), found on the brush border of the renal proximal tubular epithelial cell. Untimed urine samples from 37 normal individuals and urinary ABP less than 0.1 AU; 37 patients with pure glomerular disease had ABP less than 0.4 AU (with 29, or 76% less than 0.2 AU); 10 patients with pre-renal azotaemia had ABP less than 0.6 (with 8, or 80% less than 0.3 AU). In contrast, 79 patients with post-ischaemic acute tubular necrosis had ABP greater than 0.6 AU. Acute renal failure due to myoglobinuria, contrast dye, and aminoglycoside toxicity were all associated with urinary ABP greater than 1.0 AU. In addition, all six patients with acute bacteraemic pyelonephritis had ABP greater than 0.7 AU, as opposed to ABP less than 0.2 AU in the urines of 12 women with acute cystitis. We conclude that this monoclonal antibody based urinary assay is a sensitive measure of renal proximal tubular injury, reliably distinguishes acute tubular from glomerular disease, and may be helpful in differentiating forms of urinary tract infection.
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PMID:Diagnosis of renal proximal tubular injury by urinary immunoassay for a proximal tubular antigen, the adenosine deaminase binding protein. 288 57

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

1. Uromodulin, an immunosuppressive glycoprotein found in urine, is a high-affinity binding ligand for certain cytokines, including tumour necrosis factor. 2. Its occurrence in urine was monitored after renal transplantation to investigate whether this simple urine test might differentiate common early causes of graft failure: acute immune rejection and acute tubular necrosis. 3. Diluted urine was assayed for uromodulin using a sandwich enzyme-linked immunosorbent assay. When graft function failed due to acute tubular necrosis, urinary uromodulin levels were significantly depressed compared with levels in urine produced during biopsy-proven acute immune rejection episodes (P < 0.01) or during periods of stable graft function (P < 0.02). This suggests that urinary levels of uromodulin may reflect tubular damage rather than other causes of graft functional failure. 4. The cytokine tumour necrosis factor, which binds with high affinity to uromodulin, was found in 30% of urine samples in association with immune rejection episodes, but not during acute tubular necrosis. However, the presence of urinary tumour necrosis factor was not related to levels of uromodulin in the same sample.
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PMID:Uromodulin levels are decreased in urine during acute tubular necrosis but not during immune rejection after renal transplantation. 838 89

Tenascin, a large oligomeric glycoprotein, is a recent addition to a list of increasing extracellular matrix proteins. Previous studies have documented the strong expression of tenascin in embryonic kidney and in both normal and abnormal mature glomeruli implicating an important role of this extracellular matrix protein in nephrogenesis and glomerular scarring. Whether tenascin plays any role in interstitial fibrosis, a common final pathway of tubulointerstitial nephritis, is no known; on the other hand, a detailed knowledge of the structural components of interstitial fibrosis is essential for further studies on other fundamental aspects of this biologically and clinically important process. In this study, the expression of tenascin in the renal interstitium was immunohistochemically evaluated in 208 renal specimens during normal kidney (23 cases), acute tubular necrosis (8), acute tubulointerstitial nephritis (8), chronic primary tubulointerstitial nephritis (30), tubulointerstitial nephritis secondary to glomerular diseases of mild (46) and severe (55) degree, ischemic damage (24), and rejection (14). It was found that in normal kidney tenascin expression was limited to the medullary interstitium. In kidney with tubulointerstitial nephritis, tenascin was ubiquitously and constantly expressed in any areas with tubulointerstitial damage regardless of diagnosis, etiology, the cortical vs. medullary location of the lesions, stage of the fibrogenetic process, density of fibroblasts, or severity of interstitial inflammation in the affected areas. Indeed, strong tenascin expression was seen in areas where there was only interstitial edema or inflammation as judged by routine light microscopic preparations. In summary, this study systematically documents tenascin as a novel extracellular matrix protein selectively expressed in the medullary interstitium in normal kidney, and ubiquitously present in areas with interstitial fibrosis.
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PMID:Tenascin is an ubiquitous extracellular matrix protein of human renal interstitium in normal and pathologic conditions. 873 Apr 25

Transforming growth factor (TGF)-beta1 is important in fibrogenesis and has been involved in the pathogenesis of chronic allograft nephropathy (CAN). The angiotensinogen (AGT) gene encodes the only glycoprotein known to be a precursor of the vasopressor angiotensin II. Angiotensin II is also a growth factor and a profibrogenic cytokine. It mediates the induction of TGF-beta1. We studied the relationship among the intragraft expression of AGT, TGF-beta1, and CAN in stable renal transplant patients (RTP). We used a competitive quantitative reverse transcriptase-polymerase chain reaction (RT-PCR)-ELISA assay to identify intragraft amounts of AGT expression in RTP and correlated it with TGF-beta1 mRNA expression. We studied and performed kidney biopsies on 12 RTP with long-functioning grafts and 6 RTP in the immediate posttransplantation period (7 days) who had acute tubular necrosis as control. Histology was based on Banff working classification criteria. Total RNA was isolated from biopsy specimens. For RT-PCR-ELISA, we created heterologous RNA competitors that coamplified with the same primers as AGT and TGF-beta1. Six of 12 long RTP had proteinuria >1000 mg/24 hr and 6 had proteinuria <1000 mg/24 hr. The differences between Banff grades (P =0.03), AGT, and TGF-beta1 levels by RT-PCR-ELISA were statistically significant between both groups (106.2+/-60.7 vs. 34.1+/-11.9 pg/microg total RNA [P =0.01] and 5954+/-5612 vs. 436+/-517 transcripts/microg total RNA [P =0.01], respectively). The control group showed AGT levels of 25+/-12.2 pg/microg total RNA and TGF-beta1 levels of 228+/-111 transcripts/microg total RNA, significant only for the higher proteinuria group (P=0.01 and P=0.04, respectively). There was a correlation between AGT and TGF-beta1 in both groups (r=0.96, P=0.001). We showed a relationship between mRNA expression of AGT and TGF-beta1 in kidney transplant patients with different grades of CAN and proteinuria.
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PMID:Intragraft messenger RNA expression of angiotensinogen: relationship with transforming growth factor beta-1 and chronic allograft nephropathy in kidney transplant patients. 1235 92

Kidney injury is a deleterious side effect accompanied by therapeutic uses of cisplatin as an antineoplastic agent. However, no therapeutic option is available against this complication. This study was designed to evaluate the protective role of a glycoprotein extract obtained from Eisenia foetida against cisplatin-induced nephrotoxicity. Rats were treated with cisplatin (7.5 mg/kg, intraperitoneally, i.p.) and Eisenia foetida extract (300 and 500 mg/kg, i.p. and/or oral). Serum creatinine (Cr) and blood urea nitrogen (BUN) were significantly elevated in cisplatin-treated rats. A significant amount of lipid peroxidation was detected in drug-treated animals. Furthermore, kidney histopathological findings revealed acute tubular necrosis and hyaline cast formation caused by cisplatin. Eisenia foetida extract administration (300 and 500 mg/kg, i.p.) significantly reduced serum BUN and creatinine and lipid peroxidation in kidney tissue. Moreover, cisplatin-induced histopathological lesions were alleviated by Eisenia foetida extract. This investigation concluded that Eisenia foetida extract ameliorated cisplatin-induced nephrotoxicity. This protection might be mediated by preventing cisplatin-induced oxidative stress.
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PMID:Effect of Eisenia foetida Extract against Cisplatin-Induced Kidney Injury in Rats. 2686 51

Acute kidney injury (AKI) is characterized by acute tubular necrosis (ATN) which involves mainly proximal tubules. Past AKI is associated with higher risk of chronic kidney disease (CKD). The MUC1 mucin is a large glycoprotein responsible for epithelial protection and locates to convoluted distal tubules and collecting ducts. Since MUC1 activates the epithelial-mesenchymal transition (EMT) in carcinoma cells, we hypothesized that MUC1 could be involved in epithelial tubular cell plasticity, a process that not only accompanies epithelial repair, but also participates into kidney fibrosis, histological substratum of CKD. In cultured human proximal cells and in human kidney allograft biopsies, we observed MUC1 induction in proximal tubules displaying ATN. Transient MUC1 induction localized with mesenchymal and stem-cell markers and was associated in vitro with reduced anoikis. In a mouse ischemia-reperfusion (IR) model, Muc1 expression mitigates severe tubular injury, as WT displayed less ATN than Muc1 KO mice. But, WT mice displayed more severe kidney fibrosis than Muc1 KO 28days after ischemia. Besides, sustained Muc1 expression in WT was associated with less kidney M2 macrophages. Human kidney biopsies performed within the first week (W1) of transplantation in the context of IR showed MUC1 W1 induction associated with EMT markers. Protocol biopsies performed 3months after demonstrated sustained abnormal MUC1 induction in atrophic tubules within kidney fibrosis. Altogether these data showed that sustained abnormal MUC1 induction accompanies failing epithelial repair, chronic inflammation and kidney fibrosis. In conclusion, MUC1 exerts opposite effects during kidney response to IR: first protective and then harmful.
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PMID:Dual role of MUC1 mucin in kidney ischemia-reperfusion injury: Nephroprotector in early phase, but pro-fibrotic in late phase. 2836 75