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 macrophage cytokine tumor necrosis factor-alpha is released early in immune activation and may be detected in the peripheral circulation. This study has investigated the occurrence of plasma and urinary TNF in 30 renal allograft recipients. Although circulating TNF may be detected in 20% of pretransplant or normal control samples, levels were significantly elevated during 65% of allograft rejection episodes. Plasma TNF levels did not rise in graft failure due to acute tubular necrosis, but were always highly raised in systemic infection. In contrast, urinary TNF was only detected in association with acute rejection (49%) or tubular necrosis (14%), and no controls had detectable urinary TNF. These findings indicate that evaluation of circulating and excreted TNF may give further insight into the immunobiology of graft rejection.
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PMID:Evaluation of sequential plasma and urinary tumor necrosis factor alpha levels in renal allograft recipients. 204 98

Vascular endothelial cells express membrane bound adhesion molecules which play a direct role in the localization and subsequent movement of leucocytes from the blood into sites of inflammation. E-Selectin is a cytokine induced adhesion molecule, known to be expressed by endothelial cells in inflammatory conditions, which binds to various leucocyte subpopulations. In a prospective study we have investigated the expression and distribution of E-selectin on renal allograft needle biopsies taken from 16 pretransplant kidneys and 119 post-transplant kidneys. Post-transplant biopsies were taken at times of graft dysfunction and at times of normal graft function. Formal histology was also performed and assessed independently. E-Selectin was found predominantly on the intertubular endothelium and on the endothelium of larger vessels. E-Selectin was present, at low intensity, in some pretransplant biopsies and also some post-transplant biopsies which were reported histologically as normal. In post-transplant biopsies taken for dysfunction E-selectin was present in the majority of cases. Expression was strong in biopsies showing acute cellular rejection and this was associated with a CD4 positive cellular infiltrate. Biopsies showing other causes of dysfunction, in particular acute tubular necrosis, also were E-selectin and CD4 positive with lower intensity than those with acute cellular rejection. These results suggest that E-selectin is a good marker for endothelial activation in renal transplant biopsies. Its presence in histologically apparently normal biopsies suggests that its in vivo kinetics may differ from previously reported in vitro kinetics. E-Selectin may be a potential target for therapeutic intervention.
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PMID:The importance of E-selectin as a marker for renal transplant rejection. 753 43

E-Selectin is a 115-kDa cell surface glycoprotein transiently expressed on vascular endothelium in response to interleukin-1 and tumour necrosis factor-alpha with a peak in expression at four hours. Its distribution in transplant biopsies has been associated with inflammatory events such as allograft rejection. Recently, a soluble isoform of E-selectin has been detected in the culture medium of cytokine activated endothelial cells by an ELISA method. In this study soluble E-selectin levels in renal allograft recipients were compared with the incidence of rejection, acute tubular necrosis (ATN), cyclosporin A (CyA) toxicity, and use of orthoclone OKT3 (muromonab-CD3) to establish whether early endothelial activation and inflammatory damage could be detected. The mean soluble E-selectin level in normal volunteers was 89 ng/ml serum compared to 120 ng/ml for a group of chronic renal failure patients. Soluble E-selectin levels declined upon transplantation but this was not significant, nor was the difference in samples from patients experiencing rejection, ATN or CyA toxicity. A dramatic and sustained rise in soluble E-selectin levels was found within 24 hours of the first dose of OKT3 treatment. This study shows that soluble E-selectin does not provide early unequivocal indication of pathological sequelae in renal transplantation, although extensive endothelial activation can be demonstrated with OKT3 treatment.
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PMID:Lack of correlation of soluble E-selectin level with renal transplant rejection. 755 79

We noted previously that ischemic acute tubular necrosis (ATN) induces local expression of MHC products in renal epithelium. The present investigations were conducted to establish the role of IFN-gamma in the regulation of MHC antigen expression in ATN and to explore the changes in cytokine and growth factor expression induced by ischemic renal injury. We produced unilateral ischemic ATN in mice by clamping the left renal pedicle. MHC class I and II steady state mRNA induction was assessed by northern blot analysis, and MHC product was quantified by the extent of binding of radiolabeled monoclonals to tissue homogenates. The steady state mRNA levels for IFN-gamma, IL-2, IL-10, and granulocyte-macrophage CSF were assessed by reverse transcriptase polymerase chain reaction and the levels for transforming growth factor-beta 1 and prepro-epidermal growth factor (ppEGF) were assessed by Northern blot analysis. In the injured kidneys, steady state mRNA levels for IFN-gamma, IL-2, IL-10, granulocyte-macrophage CSF, and transforming growth factor beta-1 were increased, whereas ppEGF mRNA was markedly decreased. The MHC expression was inhibited by treatment of mice with an anti-IFN-gamma mAb (R4-6A2). Murine EGF, administered in an attempt to accelerate recovery, did not reduce the cytokine and MHC changes. These data indicate that ischemic injury, and possibly other forms of injury, triggers a complex circuit of proinflammatory cytokines. This "injury response" could be relevant to clinical renal transplants, where ATN is associated with poor graft outcome.
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PMID:Ischemic acute tubular necrosis induces an extensive local cytokine response. Evidence for induction of interferon-gamma, transforming growth factor-beta 1, granulocyte-macrophage colony-stimulating factor, interleukin-2, and interleukin-10. 787 62

Transforming growth factor beta (TGF beta 1) is a prosclerotic cytokine implicated in several disease processes. Recent reports have demonstrated a role for TGF beta 1 in experimental models of glomerulonephritis, focusing attention on the relevance of TGF beta to renal fibrogenesis in human disease. The study reported here was designed to investigate whether circulating, active TGF beta 1 could be detected in renal allograft recipients, and whether plasma levels correlated with episodes of rejection, a process involving both inflammation and fibrosis. We have developed an ELISA assay for active TGF beta 1 using commercially available antibodies, and measured plasma levels in 43 healthy controls, 11 patients with membranous nephropathy (MN) and impaired renal function, 17 transplant recipients with stable renal function, 27 patients with acute cellular rejection, 7 patients with chronic vascular rejection, and 10 patients with acute tubular necrosis and/or cyclosporine toxicity. In the last three groups diagnoses were biopsy-proved, and all samples were collected at the time of biopsy. TGF beta 1 was also measured in urine samples from 8, 11, 0, 9, 4, and 7 individuals, respectively, from each group. TGF beta 1 was not detected in plasma from any of the healthy controls or any of the MN patients, (detection limit of assay 0.1 ng/ml). By comparison, it was significantly increased in all groups of transplant recipients (unpaired t test, P < 0.01), but there were no significant differences between the transplant groups. Plasma TGF beta 1 level did not correlate with renal function (estimated by either serum creatinine or reciprocal creatinine), kidney donor age, recipient age, time since transplantation, or cyclosporine plasma trough level. TGF beta 1 was found in every urine sample tested from healthy controls, with a range from 1 ng/ml to 35 ng/ml. Among the 20 transplant patient urines tested, 2 were negative, 18 were positive but within the range determined for the healthy controls. There were no significant differences between the groups.
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PMID:Transforming growth factor beta 1 in renal allograft recipients. 801 76

In the present study the role of sCD23 determination in the management of renal graft recipients during the early postoperative period has been evaluated. In the majority of patients, increases in sCD23 serum levels were observed up to 3 days before the manifestation of an acute rejection (in 82% of cases) or infection episode (in 73% of cases), but no discrimination between these two clinical events was possible. This rise in sCD23 levels was significantly more pronounced than fluctuations observed in patients with uncomplicated courses or with graft dysfunction due to acute tubular necrosis. Serum levels of sCD23 were not influenced by excretory kidney function. These findings indicate that, in addition to its reflecting B-cell function, sCD23 may also play a role in immunological processes involving T cells and/or monocytes, thus indicating a broader range of activity of this cytokine-like molecule than has been previously assumed.
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PMID:Circulating serum levels of soluble CD23 (sCD23) after renal transplantation. 801 27

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

Cyclosporine A (CsA) is a potent immunosuppressive drug that inhibits the transcription of several proinflammatory cytokines including interleukin-2. In contrast, CsA stimulates transcription of the pleuripotent cytokine, transforming growth factor-beta (TGF beta). Since the effect of CsA in transplant recipients is unpredictable, we examined whether tissue levels of TGF beta protein in renal allografts correlate with in vivo CsA responsiveness. Intra-allograft TGF beta protein content was assessed in renal biopsies by immunohistochemical means using the mouse anti-TGF beta monoclonal antibody (Mab), 1D11. We studied 68 specimens: 21 with acute CsA toxicity (ACT), 11 with acute tubular necrosis (ATN) and 36 with acute cellular rejection (ACR). Intensity of TGF beta immunostaining was evaluated in a blinded fashion using a scale from 0 to 3+. In biopsies with histological evidence of CsA toxicity, 77% demonstrated intense (2 to 3+) TGF beta immunostaining. TGF beta protein was detected in both proximal and distal tubules but was either absent or present in low levels within glomeruli and interstitium. In contrast, only one of the 11 biopsies with ATN had minimal staining (1+) for TGF beta. The remaining 10 biopsies with ATN were negative for TGF beta immunostaining. In biopsies with ACR, the levels of renal TGF beta were more variable with 36% showing intense (2 to 3+) staining and 64% having minimal or no (0 to 1+) tubular TGF beta. Within the first 18 months post-transplantation, patients with intense TGF beta staining and ACR underwent an average of 4.1 +/- 1.8 allograft biopsies and suffered 33% graft losses. During the same period of time, the patients with ACR and absent or low (0 to 1+) TGF beta levels underwent only 2.1 +/- 1.2 biopsies, maintained better late renal function and suffered 4% graft losses. In conclusion, we demonstrate that TGF beta protein levels in renal allografts correlate with CsA effect and differentiate ACT from ATN. In CsA treated patients who develop ACR, TGF beta levels predict the subsequent clinical course and graft function. Therefore, evaluating tissue levels of TGF beta may offer unique diagnostic and prognostic benefits in the care of patients receiving CsA based immunosuppression.
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PMID:Increased renal tubular expression of transforming growth factor beta in human allografts correlates with cyclosporine toxicity. 891 30

Cellular invasion and cytokine release are important steps in the initiation of rejection. We studied the release of interleukin-8 (IL-8), a potent proinflammatory and chemotactic cytokine, and its prognostic significance in predicting rejection after renal transplantation. Serum and urine samples were analyzed with an IL-8-specific sandwich enzyme-linked immunosorbent assay. Biopsy tissue specimens (n = 20) were snap-frozen and examined with immunohistochemistry using two monoclonal antibodies against human IL-8 (4G9 and 2A8). Serum IL-8 measurements were of no value in predicting rejection due to low sensitivity (24%). In 45 biopsy-proven acute rejections (< 2 months after transplantation), urinary IL-8 concentrations were elevated in 62% (298 +/- 54 pg/mL; P < 0.01), preceding clinical diagnosis of rejection. After treatment, the IL-8 concentration in urine decreased back to normal (33 +/- 4 pg/mL; P < 0.01). The highest urinary IL-8 concentrations were seen in patients with biopsy-proven rejection in combination with acute tubular necrosis (610 +/- 150 pg/mL). This finding was independent of renal function and urinary volume. Only three of 15 rejection episodes in patients more than 2 months after transplantation showed an elevated IL-8 concentration in urine (94 +/- 60 pg/mL). In 10 of 23 patients with infection, a significant increase of IL-8 in urine was observed as well (157 +/- 67 pg/mL; P < 0.05). IL-8-positive staining was found within interstitial mononuclear cells of all biopsy specimens showing rejection. Additionally, the antibody 4G9 stained arteriolar smooth muscle and tubular cells. Interestingly, a few IL-8-positive cells were present in two donor kidneys before transplantation was performed; control tissue was negative. Further investigations are necessary to determine the clinical value of urinary IL-8 determinations in the diagnosis of rejection and to evaluate the role of IL-8 in the pathogenesis of acute allograft rejection.
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PMID:Interleukin-8 expression in patients after renal transplantation. 918 73

The rapid understanding of the cellular and molecular basis of organ function and disease will be translated during the next several decades into new therapeutic approaches to a wide range of clinical disorders, including acute renal failure (ARF). The development of the biotechnology for recombinant genetic engineering has led to the prospect of using purified protein products for therapy. In this regard, the repair of ischemic and toxic ARF is critically dependent on a redundant, interactive cytokine network of growth factors to return kidney function to near normal baseline function. Recombinant growth factors are being tested both experimentally and clinically to accelerate the repair of kidney tissue in this disorder. A newer strategy in biotechnology is the development of cell therapy derivatives. Cell therapy is based on the ability to expand specific cells in tissue culture to perform differentiated tasks and to introduce these cells into the patient either in extracorporeal circuits or as implants as drug delivery vehicles of a single protein or to provide physiological functions. Cell therapy devices are being developed to replace components of renal function that are lost during ARF and chronic renal failure and are not replaced with current hemodialysis or hemofiltration. These new approaches may result in therapeutic modalities that diminish the degree of renal failure and the time needed to recover renal function in acute tubular necrosis. This article examines the future prospects of these developing therapies in the treatment of ARF.
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PMID:Acute renal failure: growth factors, cell therapy, and gene therapy. 939 16


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