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)

Aluminum (Al) accumulation in renal failure patients can result in encephalopathy, osteomalacia, and anemia. Since the cellular mechanisms of Al toxicity are not completely understood we used cultured Friend erythroleukemia cells (FEC) as a model system of Al-induced anemia. In this system Al accumulation leads to decreased cell growth and hemoglobin synthesis despite increased iron (Fe) uptake by transferrin (Tf) endocytosis. In FEC we evaluated the effect of Al on the cellular and subcellular accumulation of Fe, ferritin concentration, the uptake of Fe by ferritin, the exit of cellular Fe, and membrane lipid peroxidation. FEC were grown in media with or without the addition of Al-Tf and studies were done at 24, 48, 72, and 96 hours after plating. The highest concentration of intracellular Al was found in mitochondria with lesser amounts in the nucleus, and the least was in cytosol. The rate of Fe uptake was higher in Al-loaded FEC without a proportionally increased rate of exit. This resulted in higher concentrations of Fe in Al-loaded FEC. Subcellular fractionation following the uptake of 59Fe, 125I-Tf in Al-loaded FEC showed increased uptake of 59Fe in the nuclear and mitochondrial compartments with no increase in the cytosol. Al-loaded FEC showed decreased ferritin content and decreased uptake of 59Fe by ferritin. Increased membrane lipid peroxidation occurred in Al-loaded FEC at 96 hours as assessed by cellular malonyldialdehyde accumulation. These results indicate that Al disrupts Fe metabolism in FEC by increasing cellular Fe content with increased compartmentalization of Fe in the mitochondria and nuclei, decreased ferritin content, and decreased uptake of Fe by ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aluminum alters the compartmentalization of iron in Friend erythroleukemia cells. 819 64

We studied 38 patients (9 haemodialysis, 18 peritoneal dialysis, 11 advanced renal failure) over the first 12 weeks of erythropoietin therapy. In 14 iron-overloaded patients (ferritin > 500 micrograms/l the haemoglobin (+/- SEM) increased from 6.74 +/- 0.27 to 9.85 +/- 0.36 g/dl (P < 0.0001) entirely by mobilizing iron reserves (reduced from 1,220 +/- 73 to 739 +/- 111 mg, P < 0.0001). In the 24 non-overloaded patients (ferritin < 500 micrograms/l) the haemoglobin rose similarly from 7.04 +/- 0.18 to 10.70 +/- 0.36 g/dl (P < 0.0001), partly from iron reserves (depleted from 200 +/- 74 to -44 +/- 77 mg, P = 0.016) and partly from oral iron supplements (305 +/- 110 mg). In the overloaded patients the ferritin declined from 1057 micrograms/l (geometric mean, range 504-3699) to 317 micrograms/l (42-1505, P < 0.0001). In the non-overloaded patients it declined from 82 micrograms/l (8-461) to 45 micrograms/l (5-379, P = 0.016). The transferrin saturation (TS) in the overloaded patients appeared to decline from 38.3 +/- 7.2% to 24.0 +/- 3.7% but this was not statistically significant. In the non-overloaded the TS was unchanged (23.3 +/- 2.4 before and 28.1 +/- 3.6% after treatment). Considering all 38 patients together, the haemoglobin correlated negatively with the ferritin (r = 0.3731, P < 0.001) but not with the TS. The TS correlated with the serum ferritin initially (r = 0.75, P < 0.001) but not after the first 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monitoring of iron requirements in renal patients on erythropoietin. 797 Jan 8

As nephron population is lost from injury or disease the remaining nephrons undergo functional and anatomic hypertrophy. The compensatory or secondary events responsible for these changes may exert a detrimental effect on the remaining nephrons that ultimately leads to their destruction. Most studies have examined how these alterations cause glomerular injury. Although glomerular injury and functional alterations are the initial result of these events, tubulointerstitial disease may be the major determinate of subsequent nephron loss and progressive renal failure. Proteinuria has been used largely as an indicator of the severity of the glomerular involvement. However, an alternative hypothesis is that the proteinuria, resulting from the glomerular injury, actually perpetuates renal injury as a result of its damaging effect on renal tubules and the surrounding interstitium. Because of being the major protein fraction it has been assumed that albumin is largely, if not solely, responsible for the induction of tubulointerstitial injury. However, with glomerular disease all protein classes can be excreted. One protein of interest is transferrin. In association with the glomerular transferrin leak, iron also would be presented to the tubule fluid. Iron is a transition element capable of catalyzing the Haber Weiss reaction with formation of hydroxyl radicals. Normally, iron is maintained in a nonreactive state in virtually all biologic tissues and fluid. However, at the reduced pH of tubule fluid iron can dissociate from transferrin and assume a reactive state capable of catalyzing hydroxyl radical formation. The kidney in patients with the nephrotic syndrome appears to be unduly susceptible to free radical injury, as documented by its increase iron content in association with depletion of copper and selenium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of iron and oxygen radicals in the progression of chronic renal failure. 831 Oct 72

Malnutrition at the initiation of dialysis is a strong predictor of subsequent increased mortality on dialysis. Few studies have documented the relationship between the progression of renal failure and spontaneous dietary protein intake (DPI) and other indices of malnutrition. In this prospective study, renal function was sequentially measured by creatinine clearance (CrCl) and DPI by 24-h urine collection; simultaneously, multiple sequential biochemical nutritional indices, including serum albumin, transferrin, prealbumin, and insulin-like growth factor-I (IGF-I) concentrations, were measured. The study involved 90 patients (46 men and 44 women) with chronic renal failure (CRF) of various causes monitored in an outpatient clinic. Dietary interventions were minimal. The mean duration of follow-up was 16.5 +/- 11.8 months. The results show that the mean (+/- SD) DPI was 1.01 +/- 0.21 g/kg per day for patients with CrCl over 50 mL/min and decreased to 0.85 +/- 0.23 g/kg per day for patients with CrCl between 25 and 50 mL/min. The DPI further decreased to a level of 0.70 +/- 0.17 g/kg per day for patients with CrCl between 10 and 25 mL/min and was 0.54 +/- 0.16 g/kg per day for patients with CrCl below 10 mL/min. This trend was statistically significant (P < 0.001). A similar statistically significant trend was observed for serum cholesterol, transferrin, and total creatinine excretion (all P < 0.01). A mixed model analysis indicated that for each 10 mL/min decrease in CrCl, DPI decreased by 0.064 +/- 0.007 g/kg per day, transferrin decreased by 16.7 +/- 4.1 mg/dL, weight decreased by 0.38 +/- 0.13% of initial weight, and IGF-I decreased by 6.2 +/- 1.9 ng/mL. It was concluded that the progression of renal failure is associated with a spontaneous decrease in DPI, especially below a CrCl of 25 mL/min, and that most nutritional indices in CRF patients worsen as CrCl and DPI decrease. Dietary protein restriction should be used cautiously in CRF patients when CrCl falls below 25 mL/min.
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PMID:Spontaneous dietary protein intake during progression of chronic renal failure. 858 13

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

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

About 30% of diabetic patients develop progressive renal failure. We studied albumin, IgG, and transferrin excretion during exercise in diabetic children without signs of nephropathy to investigate proteinuria under these conditions: 39 patients with insulin-dependent diabetes mellitus and 21 healthy children undertook a bicycle exercise test. Albuminuria measured by nephelometry was calculated as the albumin excretion rate (AER) and albumin-to-creatinine ratio before and after exercise. The diabetic group was divided into three subgroups according to disease duration (DI < 5 years, DII 5-10 years, DIII > 10 years). No significant difference in metabolic control (hemoglobin A1c was detected between the diabetic groups (median hemoglobin A1c: DI 7.2%, DII 7.6%, DIII 8.6%). There was no increase in AER in the healthy children after exercise. Before exercise the diabetic groups had an AER similar to controls. No significant increase in albuminuria after exercise was seen in group DI. Both groups with a disease duration of more than 5 years had a significant increase in albuminuria [median before/after: DII 7.8/16.7 (P < 0.05), DIII 0/57.9 (P < 0.05) micrograms/min per 1.73 m2). Of these patients, 43% also had a measurable urinary excretion of IgG and transferrin, indicating structural glomerular damage. There was no correlation of albuminuria and parameters of metabolic control or renal function. We conclude that in diabetic children an exercise test unveils albuminuria in certain patients, while their AER may be normal at rest.
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PMID:Postexercise albuminuria in children with different duration of type-1 diabetes mellitus. 889 63

In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin (EPO), a prospective randomized controlled study was designed to investigate this issue. All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 micrograms/liter were randomized into three groups with different iron supplementation: Group 1, i.v. iron dextran 5 ml every 2 weeks; Group 2, oral ferrous sulphate 200 mg tds; Group 3, no iron. All patients were treated with 25 U/kg of EPO thrice weekly subcutaneously. The hemoglobin concentration, reticulocyte count, serum ferritin, transferrin saturation, and EPO dose were monitored every two weeks for the first four months. Thirty-seven patients entered the study (12 i.v., 13 oral, 12 no iron). The three groups were equivalent with regard to age, sex, and other demographic details. Even allowing for dosage adjustments, the hemoglobin response in the group receiving i.v. iron (7.3 +/- 0.8 to 11.9 +/- 1.2 g/dl) was significantly greater than that for the other two groups (7.2 +/- 1.1 to 10.2 +/- 1.4 g/dl and 7.3 +/- 0.8 to 9.9 +/- 1.6 g/dl for Groups 2 and 3, respectively; P < 0.005 for both groups vs. Group 1 at 16 weeks). There was no difference between the groups supplemented with oral iron and no iron. Serum ferritin levels remained constant in those receiving i.v. iron (345 +/- 273 to 359 +/- 140 micrograms/liter), in contrast to the other two groups in which ferritin levels fell significantly (309 +/- 218 to 116 +/- 87 micrograms/liter and 458 +/- 206 to 131 +/- 121 micrograms/liter for Groups 2 and 3, respectively; P < 0.0005 for Group 1 vs. Group 2, and P < 0.005 for Group 1 vs. Group 3 at 16 weeks). Dosage requirements of EPO were less in Group 1 (1202 +/- 229 U/kg/16 weeks) than in Group 2 (1294 +/- 314 U/kg/16 weeks) or Group 3 (1475 +/- 311 U/kg/16 weeks; P < 0.05 vs. Group 1). The results of this study suggest that, even in iron-replete patients, those supplemented with i.v. iron have an enhanced hemoglobin response to EPO with better maintenance of iron stores and lower dosage requirements of EPO, compared with those patients receiving oral iron and no iron supplementation.
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PMID:A randomized controlled study of iron supplementation in patients treated with erythropoietin. 891 38

In patients with proteinuria, indices of tubular damage are unreliable since filtered plasma enzymes could contribute to tubular enzymuria. Previous work has suggested the existence of various forms of the 'A' isoenzyme of N-acetyl-beta, D-glucosaminidase (NAG), one of which could be kidney specific and thus a useful marker of renal tubular damage. By using fast protein liquid chromatography, two forms of the 'A' isoenzyme, 'A1' and 'A2' were separated in human urine, plasma and kidney tissue. The isoenzyme profile in pathological urine resembled that seen in kidney tissue, the 'A2' isoenzyme predominating. The ratio A2/A1 in the urine of renal patients was significantly greater than in the plasma of renal patients, end-stage renal failure patients and healthy volunteers. There was no difference in the plasma ratios of the three groups studied. The clearances of total NAG, 'A1' and 'A2' isoenzymes were all greater than that of the lower molecular weight protein transferrin. This indicates that the origin of urinary NAG in patients with proteinuria is from the kidney itself. Thus, analysis of urinary NAG and its isoenzymes may be of benefit as an early predictor of renal tubular damage and may also be useful as a non-invasive indicator of disease progression.
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PMID:Origin and significance of urinary N-acetyl-beta, D-glucosaminidase (NAG) in renal patients with proteinuria. 893 56

In progressive renal disease the degree of renal failure correlates with interstitial scarring and the rate of progression correlates with the degree of proteinuria. This has led to the hypothesis that proteinuria may cause interstitial scarring. Human tubular cells (HTC) grown on permeable membrane supports were characterized to be predominantly of proximal tubular origin. HTC produce the matrix protein fibronectin in a polarised fashion the ratio of basolateral to apical secretion being 2.9 +/- 0.2 at 48 hours. The addition of serum proteins (1.0 mg/ml) to the apical medium resulted in increased basolateral secretion of fibronectin, 2.62 +/- 0.23-fold after 24 hours and 2.40 +/- 0.16-fold after 48 hours. Serum fractionation revealed that the stimulant to fibronectin production had a molecular weight 40 to 100 kDa. Platelet derived growth factor secretion was also stimulated to apical exposure to serum but transforming growth factor beta secretion was not detected. Addition of neutralizing anti-PDGF antibodies did not decrease fibronectin secretion. The activity of serum was not reproduced by albumin or by transferrin. Exposure of HTC to serum resulted in increased release of lactate dehydrogenase, suggesting a degree of cytotoxicity. This evidence could provide a mechanism for the link between proteinuria and interstitial scarring.
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PMID:Fibronectin production by human tubular cells: the effect of apical protein. 898 25


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