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)

With a newly developed short term enzyme linked immunosorbent assay kit (TOYOBO Co.), in which 2 kinds of anti-EPO monoclonal antibodies were used, we assayed EPO concentration in sera from patients with renal failure and hematological disorders. In this report, the EPO data were analysed in relation to serum iron concentrations, with ferritin and UIBC. In the patients with renal failure, there was no significant correlation between EPO concentration and serum iron, ferritin, nor UIBC concentration. On the other hand, in the patients with hematological disorders, there were two types. One was in patients with iron deficiency anemia, whose serum EPO was negatively correlated to serum iron (r = -0.64) and ferritin (r = -0.59), but positively related to UIBC (r = 0.27). The another was the pattern in patients with aplastic anemia, leukemia and MDS, whose serum EPO positively correlated to iron and ferritin but negatively correlated to UIBC. In the patients with aplastic anemia serum EPO had good correlation to serum iron (r = 0.62), ferritin (r = 0.60) and UIBC (r = -0.46). The relationship of EPO to iron in the patients with leukemia (r = 0.54), and EPO to ferritin in the patients with MDS (r = 0.42) show significantly positive correlation coefficient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Assay of erythropoietin in serum with short term enzyme linked immunosorbent assay method--the clinical significance: Part 2--:Relation to serum iron, UIBC and ferritin in renal failure and hematological disorders]. 835 May 9

Still few data are available on efficacy and safety of recombinant erythropoietin (rEPO) in patients with myeloma and end-stage renal failure (ESRF); two such hemodialysed patients are reported in whom only partial response was observed, despite iron, folic acid supplementation and, in one case, high doses of rEPO (320 IU/kg/week). Despite improvement in well being and no need of further transfusion, hemoglobin did not reach 80 g/l. One patient developed recurrence 4 weeks after starting rEPO. Patients with ESRF and myeloma should benefit from rEPO but particular attention should be paid to marrow proliferation.
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PMID:Is erythropoietin treatment safe and effective in myeloma patients receiving hemodialysis? 840 74

Iron-dependent free radical reactions and renal ischemia are believed to be critical mediators of myohemoglobinuric acute renal failure. Thus, this study assessed whether catalytic iron exacerbates O2 deprivation-induced proximal tubular injury, thereby providing an insight into this form of renal failure. Isolated rat proximal tubular segments (PTS) were subjected to either hypoxia/reoxygenation (H/R: 27:15 min), "chemical anoxia" (antimycin A; 7.5 microM x 45 min), or continuous oxygenated incubation +/- ferrous (Fe2+) or ferric (Fe3+) iron addition. Cell injury (% lactic dehydrogenase [LDH] release), lipid peroxidation (malondialdehyde, [MDA]), and ATP depletion were assessed. Under oxygenated conditions, Fe2+ and Fe3+ each raised MDA (approximately 7-10x) and decreased ATP (approximately 25%). Fe2+, but not Fe3+, caused LDH release (31 +/- 2%). During hypoxia, Fe2+ and Fe3+ worsened ATP depletion; however, each decreased LDH release (approximately 31 to approximately 22%; P < 0.01). Fe(2+)-mediated protection was negated during reoxygenation because Fe2+ exerted its intrinsic cytotoxic effect (LDH release: Fe2+ alone, 31 +/- 2%; H/R 36 +/- 2%; H/R + Fe2+, 41 +/- 2%). However, Fe(3+)-mediated protection persisted throughout reoxygenation because it induced no direct cytotoxicity (H/R, 39 +/- 2%; H/R + Fe3+, 25 +/- 2%; P < 0.002). Fe3+ also decreased antimycin toxicity (41 +/- 4 vs. 25 +/- 3%; P < 0.001) despite inducing marked lipid peroxidation and without affecting ATP. These results indicate that catalytic iron can mitigate, rather than exacerbate, O2 deprivation/reoxygenation PTS injury.
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PMID:Inorganic iron effects on in vitro hypoxic proximal renal tubular cell injury. 843 70

Since 1991 we have used subcutaneous administration of recombinant human erythropoietin (rHuEpo) in predialysis patients selected on the basis of chronic anaemia [haemoglobin (Hb) < 7.5 g%] without any extrarenal cause and chronic renal failure with a creatinine clearance of less than 10 ml/min. rHuEpo was given to 16 predialysis patients with nephropathy, due to chronic glomerulonephritis in all 12 of the cases. The sex ratio was 1:1 and mean age was 65 +/- 9 years (range 43-87). Hb was 7 +/- 0.4 g%. rHuEpo was injected subcutaneously thrice weekly while iron was given orally systematically before rHuEpo administration. Follow-up was performed monthly until dialysis (mean 9 months). Anaemia was corrected in all cases (Hb 11 +/- 0.5 g%). Mean Epo dose was 53 +/- 26 IU/kg/week in males and 47 +/- 11 IU/kg/week in females. Iron was systematically added (Fe2+ 8.2 mg/kg/week). Every patient had improved physical and intellectual ability after rHuEpo within the first month. No adverse side effects were noted but all patients were under antihypertensive therapy (one to three drugs). Serum potassium was unchanged. Mean creatinine before treatment was 507 mumol/l, and was 820 mumol/l after the treatment. Progression of renal failure was only affected by rHuEpo in one patient. In this case renal failure progression decreased. There was no significant alteration in the slope of the creatinine curve from 12 months before to after rHuEpo. Ten patients underwent dialysis (five CAPD, five haemodialysis), while six remained dialysis free. From January 1991 to December 1993 rHuEpo was given to 12.3% of the end-stage renal failure patients on dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Subcutaneous erythropoietin administration in predialysis patients: a single centre prospective study. 852 92

The cause of the relentless progression of chronic renal failure of diverse origins remains unknown and is likely to be multifactorial. Numerous studies have now demonstrated a correlation between the degree of proteinuria and the rate progression of renal failure, which has led to the hypothesis that proteinuria may be an independent mediator of progression rather than simply being a marker of glomerular dysfunction. This article reviews the evidence underlying this hypothesis and the mechanisms by which particular proteins may cause renal pathology. The abnormal filtration of proteins across the glomerular basement membrane will bring them into contact with the mesangium and with the tubular cells. There is evidence to support a role of lipoproteins on mesangial cell function, which ultimately could contribute to glomerular sclerosis. The proximal tubular cells reabsorb proteins from the tubular fluid, which leaves them particularly vulnerable to any adverse effects proteins may have. It has been postulated that the sheer amount of protein to be metabolized by these cells may overwhelm the lysosomes and result in leakage of cytotoxic enzymes into the cells. In addition, the increased metabolism of proteins may result in production of ammonia, which can mediate inflammation through activation of complement. Specific proteins that have been shown to be cytotoxic are transferrin/iron, low-density lipoprotein, and complement components, all of which appear in the urine in proteinuric states. Other specific proteins have been shown to stimulate production of cytokines, chemoattractants, and matrix proteins by tubular cells and thus may stimulate interstitial inflammation and scarring. The mechanisms by which the presence of proteins in the tubular fluid alters tubular cell biology is yet to be determined.
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PMID:The role of proteinuria in the progression of chronic renal failure. 865 Dec 39

The pathogenesis of the anemia of cancer involves the combination of a shortened erythrocyte survival in circulation with the failure of bone marrow to increase red cell production in compensation. Inappropriate red cell production is itself related to a conjunction of factors, including impaired availability of reticuloendothelial storage iron, inadequate erythropoietin (Epo) response to anemia, and overproduction of cytokines which are capable of inhibiting erythropoiesis. Many of these cytokines may interfere with erythropoietin production by the kidney. Consequently inadequate serum erythropoietin levels are often encountered in cancer patients, though more frequently in those with solid tumors or multiple myeloma than in those with other hematologic malignancies. There is little evidence supporting a negative impact of chemotherapy, including cisplatin, on erythropoietin production. Rather, chemotherapy usually causes a transient elevation of serum Epo. Red cell transfusions are often administered to cancer patients, possibly resulting, among other deleterious effects, in enhancement of tumor growth. Recombinant human erythropoietin (rHuEpo) has thus been proposed as an alternative. RHuEpo has been shown to be safe and effective in correcting the anemia of cancer and reducing the need for transfusions. The response rate is as good in hematologic malignancies as in solid tumors, but it is extremely poor in those with myelodysplastic syndromes. The effect of rHuEpo does not differ among patients receiving or not receiving chemotherapy, including cisplatin. The probability of response is also similar in patients with adequate or inappropriate erythropoietin production before therapy, although the doses used are usually 2 to 3 times higher than in renal failure patients.
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PMID:Erythropoietin and the anemia of cancer. 866 61

Both the plasma determinations of erythropoietic (EPO) and transferrin receptor (TfR) would provide a good characterization of anemia especially when mixed erythron disorders underlie, such as in renal failure. Immunologic assays of EPO and TfR, as well as standard hematologic determinations (hematocrit, reticulocyte count, serum iron, transferrin, ferritin) were performed in patients with chronic renal failure (CRF), in regular dialysis treatment (RDT) and in transplanted (TX) patients. In nonanemic TX patients both EPO and TfR ranged normally, whereas in anemic TX ones (Hct < 40%) both values were increased suggesting the physiologic response both of the kidney and of the erythron to decreased red cell mass. In transitory posttransplant erythrocytosis the increased values of TfR, with normal EPO values, would hypothesize a defective feedback to EPO release. Both EPO and TfR values were found increased in TX patients with adult polycystic kidney disease with persistent erythrocytosis (Hct > 50%), thus confirming previous observations. In CRF and RDT patients, all anemic, both EPO and TfR were normal, even though significantly low with respect to the degree of anemia. In RDT seriously anemic patients, the administration of recombinant human EPO induced different patterns of bone marrow response. We conclude that the determination of TfR would provide further information on renal anemia since the receptor increase mostly preceded the rise of Hct, evidencing those patients who will not have an effective bone marrow response to the therapy.
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PMID:The determination of plasma transferrin receptor as good index of erythropoietic activity in renal anemia and after renal transplantation. 873 Apr 20

Advanced glycation endproducts (AGEs), structural components of beta-amyloid plaques and neurofibrillary tangels, have been implicated in the pathogenesis of Alzheimer's disease. AGE levels, measured by fluorescence, and their precursor molecules such as glucose and its Amadori product, fructosylamine, were measured to examine the question whether the reported increased level of AGEs in the brain is reflected in an increase in AGE-associated parameters in peripheral blood. Lactoferrin, proposed to play an important role in the interaction of AGEs with their receptors, was determined by ELISA. All AGE-associated parameters showed trends to lower values in patients with Alzheimer's disease compared with non-demented controls. Albumin and total iron were not significantly different between the groups. In contrast to diabetes and renal failure, where high levels of AGEs and their precursors are present in tissue as well as in peripheral blood, elevated CNS AGE levels in patients with Alzheimer's disease are manifested without detectable peripheral changes.
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PMID:Advanced glycation endproducts-associated parameters in the peripheral blood of patients with Alzheimer's disease. 876 Oct 18

Aluminum (Al) is unquestionably neurotoxic in both experimental animals and certain human diseases. Minute quantities injected intracerebrally into rabbits will induce severe neurological symptoms and neuropathological features of neurodegeneration. Hyper-aluminemia often develops in patients with renal failure being treated with intermittent hemodialysis on a chronic basis, and in severe cases results in an encephalopathy. Uremic adults and premature infants not on dialysis treatment also can develop encephalopathy due to Al toxicity, as is the case when large amounts of alum are used as a urinary bladder irrigant. There are many other examples of Al-induced neurotoxicity; however, the question as to whether Al presents a health hazard to humans as a contributing factor to Alzheimer's disease is still the subject of debate. Several lines of evidence are presented that have formed the basis of the debate concerning the possible pathogenic role for Al in Alzheimer's disease. Important evidence for an Al-Alzheimer's causal relationship is the observation by laser microprobe mass analysis (LMMS) of the presence of Al in neurofibrillary tangles, although there are conflicting data on the extent of the Al deposition. The relatively poor sensitivity of some of the analytical instruments available for these challenging in situ microanalyses could explain the discrepant results, although LMMS and perhaps secondary ion mass spectrometry (SIMS) appear to be sufficiently sensitive. Harmonization of the techniques is an essential next step. There is new evidence that exposure to Al from drinking water might result in cognitive impairment and an increased incidence of Alzheimer's disease. However, these epidemiological studies have inherent problems that must be scrutinized to determine if an association really does exist. An understanding of a possible enhanced bioavailability of Al in this type of exposure, versus other exposures such as antacid intake or industrial exposure, needs to be considered and explored. There has been one promising clinical trial of the treatment of Alzheimer's disease patients with the Al chelator desferrioxamine (DFO). Further studies are needed, and if confirmation is forthcoming then such data could also support an Al-Alzheimer's disease link as well as suggesting that DFO offers potential as a therapeutic agent. The possibility that iron might be the offending agent needs to be considered since DFO is a very strong iron chelator. The significance of Al-induced neurofibrillary degeneration in experimental animals should be assessed especially in light of new data showing that this model exhibits abnormally phosphorylated tau protein structures in the neuronal perikarya. Thus the key questions that must be answered before it can be asserted that Al possesses causal relationship to Alzheimer's disease, are as follows and are addressed in this present discussion: (1) Are there elevations of the concentration of Al in the brains of Alzheimer's disease patients? (2) Is there a relationship between environmental exposure to Al, particularly in drinking water, and an increased risk of Alzheimer's disease? (3) Is treatment with DFO a potentially useful therapeutic approach and to what extent might beneficial effects of DFO implicate Al in the etiology of Alzheimer's disease? (4) Are there similarities between the experimental animal studies and Alzheimer's disease particularly in the development of abnormal forms of tau seen in neurofibrillary tangles? (5) Does Al promote the deposition of the A beta peptide in Alzheimer's disease? (6) Does hyperaluminemia associated with long-term hemodialysis treatment induce neurofibrillary degeneration? If the answer to each of these six questions is yes, then does this assert that Al possesses a causal relationship to Alzheimer's disease? On the other hand, must all six be met to be able to make this assertion?
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PMID:Can the controversy of the role of aluminum in Alzheimer's disease be resolved? What are the suggested approaches to this controversy and methodological issues to be considered? 877 2

That bone disease accompanies renal failure has been known for over 100 years. This bone disease (renal osteodystrophy) has been variously attributed to hyperparathyroidism, vitamin D deficiency, aluminium toxicity, iron toxicity, uraemia, and a host of other aetiologies. In addition, the form the bone disease takes has been variously described as osteitis fibrosa, osteomalacia, mixed uraemic osteodystrophy and the aplastic (adynamic) lesion. In this manuscript we will focus on the aetiology, consequences, diagnosis and possible management of the aplastic form of the disease. The renal osteodystrophy study was a prospective, cross-sectional study of renal bone disease in a largely unselected population of patients receiving dialysis in three hospitals in Toronto. A variety of non-invasive data (parathyroid hormone (PTH), aluminium, etc.) and bone histology were obtained and analysed to assess pathogenesis, diagnostic criteria and management. We have defined the aplastic lesion as having low bone formation without a marked increase in unmineralized osteoid (i.e. excluding osteomalacia). We have noted that it may be associated with increased aluminium or little to no aluminium. With increased aluminium the patients have a poorer prognosis both with regards to bone disease and mortality, and they should be managed appropriately to alleviate aluminium toxicity. With lesser amounts of aluminium, morbidity and mortality are less severely impacted, but not normal. We have shown that the low bone formation, of the aplastic lesion without aluminium may be "normalized' by increasing PTH levels. It is concluded that aplastic bone disease carries adverse consequences both in terms of bone problems and survival. In the absence of aluminium toxicity the stimulation of PTH effectively corrects the bone formation abnormality. Whether this will alleviate the adverse consequences will be difficult to study. Avoiding the problem by not over-suppressing PTH seems a reasonable approach at this point.
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PMID:The aplastic form of renal osteodystrophy. 884 Mar 8


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