Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We administered a 12-week course of cyclosporine (CsA) (4 to 6 mg/kg/24 h) to nephrotic patients with membranous glomerulopathy (MG). Nephrotic patients with minimal change nephropathy (MCN) served as a comparison group. We evaluated the effects of CsA on proteinuria, glomerular function, and the release of cytokines by peripheral blood mononuclear cells in culture. Proteinuria was restored to normal levels within 2 to 4 weeks in MCN. Proteinuria declined from nephrotic to subnephrotic levels (< 3,500 mg/24 h) in 10 of 14 patients with MG, also within 2 to 4 weeks of onset of therapy. The four nonresponders exhibited a rapidly progressive and presumably irreversible form of MG culminating in renal failure. On average, fractional clearances of albumin and IgG declined by 59% and 73% in MG (P < 0.005); corresponding declines in MCN were by 99% (P < .0001). Corresponding rates of glomerular filtration in each glomerular injury remained unchanged. A strong trend for proteinuria to relapse after CsA was withdrawn was evident in both disorders. The release of tumor necrosis factor (TNF)-alpha by mononuclear cells in culture was enhanced in each glomerular injury, both before and after the course of CsA. We conclude that the proteinuria in most cases of MG exhibits a responsiveness to CsA that is qualitatively similar to, but less complete than, that in MCN. The rapidity with which barrier function improves suggests a possible role for cell-mediated immune injury in MG.
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PMID:Short-term responsiveness of membranous glomerulopathy to cyclosporine. 848 28

Polycystic kidney disease is an inherited disorder of parenchymal structure that leads to renal failure. Cysts begin as focal dilations in proximal tubules and collecting ducts, giving rise to cyst walls lined by a phenotypically disturbed epithelium that expresses dysfunctional transport and matrix proteins. We used an mRNA search protocol to probe efficiently for tissue-specific disturbances that might underlie the formation of cysts. This search assessed the relative abundance of transcripts encoding a variety of growth factors (transforming growth factor-beta 1, interleukin-6, tumor necrosis factor, and endothelin-1), structural proteins (collagen IV, nidogen, fibronectin, and laminins A and B1), and cell adhesion molecules (CAMs; E-cadherin, N-CAM, laminin receptor, and fibronectin receptor) in the cystic kidneys of cpk/cpk mice and uncovered a previously unrecognized early reduction in mRNA encoding N-CAM (54%) and E-cadherin (56%) (n = 5; P less than 0.001). Levels of transcripts for growth factors, structural proteins, and for fibronectin and laminin receptors in normal and cystic kidneys were generally similar. The reduction in transcripts for N-CAM and E-cadherin in kidneys from cystic mice was not observed in autologous liver. The immunofluorescent staining of cystic kidneys confirmed that the decrease in N-CAM and E-cadherin was generally confined to regions abundant in developing cystic epithelium. The presence of both N-CAM and E-cadherin appears to guide the sequential differentiation and polarization of normal renal epithelium, and their attenuated expression in the kidney of cpk/cpk mice may be a material factor contributing to the pathogenesis of cyst formation.
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PMID:Attenuated expression of epithelial cell adhesion molecules in murine polycystic kidney disease. 156 81

Three hybridoma cell lines secreting monoclonal IgG antibodies specific for human tumor necrosis factor-binding protein I (TNF-BP I), the extracellular domain of the 60 kDa TNF receptor, were developed by fusion of spleen cells from mice immunized with TNF-BP I purified from urine. The antibodies recognize three different epitopes on TNF-BP I. Two of the antibodies were used to develop a two-site ('sandwich') enzyme immunoassay with horseradish peroxidase as the marker enzyme. The assay was able to measure TNF-BP I in serum, urine and cell culture supernatants with a sensitivity of about 200 ng/l and a precision better than 10%. TNF-BP I was detected in the serum of healthy individuals at a mean concentration of 2.1 +/- 1.0 micrograms/l (mean +/- standard deviation; range, 0.52-5.4 microgram/l, n = 42); no significant difference was seen in patients with chronic polyarthritis (2.3 +/- 0.79 micrograms/l; n = 15). Serum TNF-BP I was significantly elevated in patients with burns (6.5 +/- 1.7 micrograms/l; n = 10) and markedly increased in patients with renal failure (49 +/- 17 micrograms/l; n = 6). TNF-BP I was also detectable in urine from normal individuals (2.2 +/- 1.2 micrograms/l; range 0.78-4.3 micrograms/l; n = 16). Culture supernatants of several human tumor cell lines also contained TNF-BP I. The assay will be a useful tool to detect activation of the TNF receptor by the physiological ligands, TNF-alpha and TNF-beta, as well as transmodulation by other mediators in various pathological conditions.
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PMID:A monoclonal antibody-based enzyme immunoassay for quantitation of human tumor necrosis factor binding protein I, a soluble fragment of the 60 kDa TNF receptor, in biological fluids. 191 33

Phagocytosis is the process where specific cells, phagocytes, ingest foreign material, include it in a cytoplasmatic vacuole, called phagosome, and destroy it. The function of phagocytosis in the immune response has been underevaluated for a very long time. Phagocytosis however, appears to be more and more important in our defense against infection and cancer. The uremic patient presents a well known and increased tendency for infectious disease as well as an increased incidence of cancer. Modern methodology for investigation of phagocytic function consists of: 1. measuring the respiratory burst during phagocytosis; by examining the radio-active CO2 production during the glucose metabolization of phagocytosis. 2. During the chemical reaction of the respiratory burst light is produced. This chemiluminescence can be measured in a Lumetron. In uremia the registration of that chemiluminescence can however be disturbed by the presence of uremic toxins, acting as scavengers of free radicals. 3. Measurement of interleukin-1, interleukin-6 or tumor necrosis factor production during phagocytosis. In the present study, we investigated glucose metabolization and radioactive CO2 production without stimulation and after a challenge with Latex, Zymosan or Staphylococcus Aureus. All tests have been performed on 50 microliter whole blood samples. The following uremic situations have been investigated: 1. Several degrees of increasing renal failure. 2. First weeks of hemodialysis maintenance treatment. 3. Hemodialysis session. 4. Course of hemodialysis maintenance treatment. 5. Continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. 6. Changes after chemical stimulation by a cephalosporin (cefodizime (R)). The Authors report their detailed results of these investigations and conclude as follows: --uremia is a prototype of acquired immune deficiency. --Contact with bio-incompatible membranes during hemodialysis is disastrous for phagocytosis. --Other toxins than the classical urea or creatinine are apparently responsible for the phagocytic disturbances. --Stimulations of phagocytosis with medication such as the cephalosporin, Cefodizime(R) (Hoechst) is possible.
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PMID:[Phagocyte function in uremic patients]. 192 26

In this study the interaction of endotoxemia and ischemic organ injury was investigated in a rat model. Animals received lipopolysaccharide to induce endotoxemia and were simultaneously subjected to renal ischemia. If only renal ischemia was induced, moderate azotemia occurred and all animals survived. Lipopolysaccharide treatment caused neither renal failure nor death. However, rats with both endotoxemia and renal ischemia showed severe azotemia, and 50% of the animals died within 48 hours. The observed mortality rate is unlikely related to renal failure since animals subjected to bilateral nephrectomy did not die within 48 hours after treatment with lipopolysaccharide. To further exclude the role of renal failure in the enhanced effect of endotoxemia, experiments were performed in which ischemic kidneys were excised from littermates and were placed in the abdomens of lipopolysaccharide-treated animals. A similar effect was observed: 50% of the animals died within 48 hours. Azotemia did not occur. Since tumor necrosis factor (TNF) is an important cytokine involved in endotoxemia-induced morbidity and death, we studied the role of TNF in our model. Plasma levels of TNF were increased during endotoxemia. Concomitant renal ischemic injury did not influence the concentration of TNF. When animals were treated with recombinant TNF and were subsequently subjected to renal ischemic injury, again a 50% mortality was observed, a rate similar to that in lipopolysaccharide-treated animals. We conclude that the sensitivity to endotoxemia is enhanced by tissue necrosis and may lead to death in the experimental model used in this study.
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PMID:Increased sensitivity to endotoxemia by tissue necrosis. 199 49

We reviewed treatment and prognosis in 7 operative and 7 non-operative cases of renal cell carcinoma with venous tumor thrombosis formation, 14 cases in total. Treatment after around 1983 involved the use of biological response modifier (BRM), chiefly interferon (IFN), and operation by thoracoabdominal approach. Before that, chemotherapy, radiotherapy and operation by peritoneal approach were used, with many cases judged inoperable. Even in non-operative cases, life-prolongation was frequently achieved by embolization of the renal artery and administration of various BRMs. On the other hand, in cases judged operable which were always treated by resection, early postoperative death sometimes occurred. These facts brought home to us the difficulty of choosing appropriate treatment. Though it is hard to determine the relative merits of various treatments from the present data, since the series is small and contains cases from 1963 onwards, the clinical and pathological pictures should be carefully evaluated for each case, and the most suitable course of treatment should be selected individually. We describe a non-operative case in which a combined use of embolization, IFN-gamma and tumor necrosis factor (TNF) elicited a lasting partial response, and an operative case in which postoperative complications such as pulmonary infarction and renal failure occurred after operation under extracorporeal circulation and patient died at 2 months after operation.
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PMID:[Clinical analysis of renal cell carcinoma with intravenous tumor thrombus]. 227 14

Using an enzyme-linked immunosorbent assay, we measured plasma levels of tumor necrosis factor (TNF) in 38 patients who were treated with either antilipid A antibody or a placebo for presumed gram-negative bacteremia. Sixteen of the 38 patients had positive blood cultures: 14 with gram-negative rods and 2 with Streptococcus pneumoniae. Initial serum samples for TNF determinations were obtained within 2 to 72 hours (mean, 18.8 hours) after the onset of clinical signs of sepsis. Six (16%) of 38 patients had detectable TNF levels: 4 of 14 with positive blood cultures for gram-negative rods but only 2 of 22 with negative blood cultures (odds ratio, 4; 95% confidence limits, 0.5 and 24.3). Of the 6 patients, 4 had received the placebo and 2 had received the antibody. Tumor necrosis factor levels did not predict adult respiratory distress syndrome, shock, disseminated intravascular coagulation, renal failure, or mortality. The highest TNF levels (500 and 250 pg/mL) were observed in 2 patients with Enterobacter cloacae bacteremia who had received the placebo and antilipid A antibody, respectively. The other 2 patients with bacteremia and detectable TNF levels had positive blood cultures for Haemophilus influenzae (50 pg/mL) and Bacteroides fragilis (120 pg/mL), respectively. Despite negative blood cultures, the remaining 2 patients repeatedly had detectable TNF levels and a clinical picture consistent with gram-negative sepsis.
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PMID:Plasma tumor necrosis factor levels in patients with presumed sepsis. Results in those treated with antilipid A antibody vs placebo. 230 78

The close similarities between the biological effects of proinflammatory cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), and the clinical symptoms observed in patients on HD have promoted the concept that cytokine production induced during dialysis could have a role in dialysis-related symptoms. However, over the last decade the discovery of cytokine-specific inhibitory proteins such as IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptors (sTNFR), has raised new questions concerning the role of cytokines in dialysis-related morbidity. In HD patients, the molar ratios of plasma IL-1Ra:IL-1 beta range from 3:1 to 4:1 and the molar ratios of plasma sTNFR:TNF range from 13:1 to 38:1. Likewise, in patients on chronic HD with cuprophan membranes, peripheral blood mononuclear cell (PBMC) content of IL-1Ra in freshly obtained PBMC as well as the production of IL-1Ra by endotoxin-stimulated PBMC from these HD patients was several-fold higher than that in undialyzed patients with CRF, CAPD patients or healthy controls. In fact, endotoxin-stimulated PBMC from all three groups of patients with renal failure produced significantly more IL-1Ra than IL-1 beta. These findings raise the issue whether the production of cytokine-specific inhibitors observed in patients on HD are of functional significance or serve as markers of inflammation. In vivo studies have shown that a 1,000-fold excess of IL-1Ra is required to block the hemodynamic effects of IL-1. Therefore, it is unlikely that the levels of IL-1Ra and sTNFR observed in patients on HD are sufficient to block the systemic effects of IL-1 and TNF produced during dialysis. Therefore, elevated plasma levels of inhibitory proteins such as IL-1Ra and sTNRF are more likely to be 'footprints' of IL-1 and TNF, respectively, produced during dialysis.
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PMID:Cytokine production in patients on dialysis. 761 85

This paper is divided into a retrospective descriptive section in which we report on three distinctly different and spontaneous responses of the baboon to LD100 Eschericia coli observed over the last 6 years. This section is followed by an experimental section in which we reproduce the immediate and delayed responses based on hypothetical mechanisms. In the descriptive section, we arbitrarily divided all the non-survivor animals on which we had sufficient data into three groups based on duration of survival (i.e., 12 hr or less, immediate, 12 to 30 hr, intermediate, and 30 hr or more, delayed). The natural history and pathophysiology of the 12 hr or less group matched that of capillary leak syndrome with a rapid fall in blood pressure, rise in hematocrit, massive edema, and congestion with leukocyte sequestration in both lung and liver, with only limited adrenal cortical hemorrhage. The 12 to 30 hr group matched the natural history of a consumptive hemorrhagic diatheses with a biophasic blood pressure response, limited change in hematocrit, a severe consumptive coagulopathy, severe adrenal cortical hemorrhage, and a moderate renal cortical tubular necrosis, but limited renal cortical thrombosis. The greater than 30 hr group matched the natural history of a microvascular thrombotic (hemolytic uremic) syndrome with a stable blood pressure, a fall in hematocrit associated with a massive renal cortical thrombosis with a severe medullary, and cortical tubular necrosis. We did not analyze these groups further (i.e., type of intervention etc.) once we found that time of survival correlated with a unique clinical syndrome, because based on these observations, we hypothesized that we could reproduce the immediate capillary leak and pulmonary failure, and the delayed microvascular thrombosis and renal failure syndromes experimentally. We reproduced the immediate (< 12 hr) and delayed (> 30 hr) responses by infusion of either tumor necrosis factor or C4b binding protein with sublethal E. coli. This provides models of the immediate and delayed as well as the intermediate responses to E. coli for study of mechanism and the efficacy of therapeutic interventions.
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PMID:Retrospective description and experimental reconstitution of three different responses of the baboon to lethal E. coli. 801 66

Cellular release of cytokines may be responsible for certain complications of extracorporeal dialysis including the increased susceptibility to infection found in dialysis patients. In order to study this further, we have evaluated the in vitro production of tumor necrosis factor (TNF) by peripheral blood monocytes (PBMC) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure (ESRF). The patients were subdivided into two groups according to the type of dialysis; those undergoing hemodialysis (HD) (N = 12) and those performing continuous ambulatory peritoneal dialysis (CAPD) (N = 9). Results were compared with those of controls taken from healthy laboratory staff (N = 7). The experiments show that the secretion of TNF by PBMC's in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 U/ml vs. 18.2 + 13.3 U/ml, mean +/- SD, P < 0.001); and controls (81.3 +/- 38.7 U/ml vs. 18.1 +/- 6.6 U/ml, P < 0.001). There was no significant difference between the CAPD group and controls. In vitro monocyte production of TNF fell following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, P < 0.05). We conclude from this study that TNF release from PBMC's in vitro is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD. Interestingly, TNF release from monocytes collected immediately following a dialysis was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro production of tumor necrosis factor by monocytes cultured from dialysis patients. 832 Sep 27


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