Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven children aged 0.6-17 years with preterminal chronic renal failure and anemia (mean serum creatinine concentration 4.8 mg/dl; mean hemoglobin concentration 7.9 g/dl) were treated with sc injections of recombinant human erythropoietin (EPO, initial dose 150 U/kg/week) over a mean period of 13 months. When a target hemoglobin concentration of 11.5-13.5 g/dl was reached, the dose was adapted. Iron deficiency was corrected. Hemoglobin concentration increased by > 2 g/dl in all patients within 14-119 (mean 45) days. The last maintenance dose ranged between 75 and 300 (mean 133) U/kg/week. No major adverse effects were observed, except for hypertension which occurred in about half of the patients and necessitated interruption of EPO in one child with advanced renal failure. Additional antihypertensive drugs were given to five patients. Body height increased in two patients by 0.6 and 1.3 SDS/year, respectively. In six patients with a mean observation period of 14 months before and 16 months after the start of EPO, the mean slope of the reciprocal serum creatinine concentration curve improved slightly (p = 0.05). The proposed schedule appears to be safe for the treatment of renal anemia in most pre-dialysis patients. Frequent monitoring of hemoglobin, blood pressure, serum creatinine and ferritin is required.
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PMID:Treatment of renal anemia by subcutaneous erythropoietin in children with preterminal chronic renal failure. 811 Nov 77

Recombinant human erythropoietin was given to eight children and adolescents with stable chronic renal failure in the predialysis state. The hormone was administered subcutaneously, twice weekly for 12 weeks, at a starting dose of 50 U/kg per week. The dosage was adapted every 4th week. Target haemoglobin was 10.5-11.5 g/dl, and the target haematocrit 32%-35%. Baseline haemoglobin levels of 8.20 +/- 0.93 g/dl increased to 9.17 +/- 1.10, 10.38 +/- 1.18 and 11.19 +/- 0.84 g/dl (mean +/- SD) after 4, 8 and 12 weeks respectively. Serum ferritin levels decreased progressively despite iron supplementation. No side-effects were observed: creatinine clearances remained stable, blood pressure did not increase and none of the patients displayed either convulsions or thrombotic features. The study shows that subcutaneous recombinant human erythropoietin is both effective and safe in anaemic children and adolescents with chronic renal insufficiency.
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PMID:Subcutaneous recombinant erythropoietin in preterminal renal insufficiency. 815 20

Nephrotoxic lesions induced by cisplatin in rats are characterized by acute tubular necrosis in the outer stripe of the medulla. The purpose of this study was to examine the potential role of changes in metal binding proteins, and iron and copper content in urine and renal tissue in cisplatin-induced nephrotoxicity. Cisplatin was administered intravenously to groups of 20 rats at single doses of 0, 1, 2.5, and 5 mg/kg and rats were sacrificed at 1, 2, 3 and 6 days after treatment. Increased serum BUN and creatinine were observed at a dose of 5 mg/kg cisplatin on day 2 through day 6. Increased urinary copper excretion coincided with necrosis and increased BUN and creatinine on day 3 in the high-dose group. Evidence of renal injury was apparent histologically as karyomegaly at all dose levels as early as 48 hours after injection of cisplatin, prior to increases in urinary copper levels. No change in the distribution of metal binding proteins (transferrin, ferritin, ceruloplasmin, and metallothionein) evaluated by immunohistochemical staining, was seen. Based upon these results, it is unlikely that changes in metal excretion play a primary role in cisplatin-induced nephrotoxicity however, changes in nuclear function indicated by karyomegaly may be involved in early renal injury.
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PMID:Assessment of the possible role of iron and copper in cisplatin-induced nephrotoxicity in the rat. 816 68

Although polymorphonuclear (PMNL) glucose consumption as an index of metabolic response to phagocytosis in the production of free radical species is depressed in hemodialyzed patients, substantial interindividual differences are registered. Studies evaluating to what variables these differences are related are, however, lacking. In the present study, the relation of several factors to PMNL functional capacity in the breakdown of glucose to CO2 by the hexose monophosphate shunt (HMS) is considered in an individual and multifactorial regression analysis. Starting from a database, collected in 126 stabilized hemodialysis patients, PMNL HMS-response to standard quantities of latex and zymosan was correlated to 14 numerical parameters: time since the start of dialysis, hematocrit, serum creatinine, phosphorus, ferritin, albumin, parathormone, albumin before and after administration of desferrioxamine, residual creatinine clearance, PCR, TACurea, Kt/V and age. In addition, the non-numeric parameters of sex, biocompatibility of dialyzers, and primary diagnosis were also considered. A significant correlation was found for time on dialysis (P < 0.001), hematocrit (P < 0.001), ferritin (P < 0.05), PTH (P < 0.001) and aluminum (P < 0.05). The highest correlation coefficients were found for time on dialysis (latex: N = 126, r = 0.50, P < 0.001; zymosan: N = 126, r = 0.58, P < 0.001). Multivariate correlation analysis of one clinical parameter together with time on dialysis to PMNL response showed that the correlation was strongly weakened or disappeared for ferritin, aluminum and PTH, but not for hematocrit. Our data indicate that time since the start of dialysis is an important, but not unique factor, influencing polymorphonuclear functional capacity in a hemodialysis population.
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PMID:Contributing factors to the inhibition of phagocytosis in hemodialyzed patients. 835 62

Regulation of renal erythropoietin (EPO) production has not yet been clearly established in physiologic as well as in pathologic conditions. Recent studies suggest a possible role for renin-angiotensin system in control of EPO production. An elevation in blood pressure occurs commonly in patients with various forms of anaemia treated with recombinant human EPO. Furthermore it has been found that EPO can alter secretion of hormones engaged in regulation of intravascular fluid volume and vascular resistance. The aim of this study was to determine whether patients with essential hypertension (EH) and healthy subjects differ in EPO secretion and whether EPO serum level is related to renin response to dietary sodium restriction and upright position of the body. 63 patients with EH and 12 healthy subjects were investigated. Patients with EH were divided into subgroups on the following criteria: renin response to dietary sodium restriction and upright position of the body. 63 patients with EH and 12 healthy subjects were investigated. Patients with EH were divided into subgroups on the following criteria: renin response to dietary sodium restriction and upright position of the body and severity of existing hypertension. In all subjects haematocrit value, haemoglobin concentration, erythrocyte count, sodium, potassium, creatinine, iron, ferritin serum levels, total iron binding capacity, plasma renin activity (PRA), erythropoietin serum level and mean arterial blood pressure (MAP) were measured in basic conditions (normal sodium diet). Additionally PRA, EPO and MAP were measured after dietary sodium restriction for three days and upright position of the body for three hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Relation between erythropoietin production and plasma renin activity in patients with essential hypertension]. 841 37

An evaluation of 26 surviving outpatient lung transplant recipients at one center showed that 65% (17/26) had significant anemia (hemoglobin < 11 g/L for women, < 14 g/dl for men) at a median follow-up of 13.5 months after transplantation (range, 1-41 months). There were 14 men and 12 women with a mean age of 45.1 years (range, 23.1-66.7 years). Fifteen had a double allograft and 11 had a single allograft. Anemia was normochromic and normocytic/macrocytic with a tendency to anisocytosis, with normal reticulocyte counts. Iron deficiency (transferrin saturation < 20%) was found in 35% (6/17) of anemic patients, and two of them also had ferritin levels < 15 micrograms/L. In addition, vitamin B12 was decreased in 1 patient. Folate levels were all normal. Erythropoietin levels were significantly decreased in anemic lung transplant recipients as compared with nontransplanted iron-deficient anemic patients (median, 1 mU/ml, range 1-41 mU/ml, vs. 53 mU/ml, 15-88 mU/ml; P < 0.05). In nonanemic lung transplant recipients, erythropoietin levels were decreased too, as compared with normal controls (median, 2 mU/ml, range 1-21 mU/ml, vs. 5 mU/ml, 3-32 mU/ml; P < 0.05). Investigation of peripheral stem cells in 9 patients showed normal stimulation of erythroids (burst-forming unit, erythroid; median, 573 cells/ml; range, 128-1898 cells/ml) independent of erythropoietin concentrations. Analysis of putative prognostic factors, such as age, surgical procedure (double vs. single lung allograft), indication for transplantation, time after transplantation, infection status, presence of bronchiolitis obliterans, immunosuppression (+/- azathioprine), serum creatinine, creatinine clearance, hypertension, and arterial partial pressure of oxygen, did not demonstrate any difference in erythropoietin concentrations. Only the sex variable revealed a trend to higher levels in women than in men (median, 4 mU/ml, range 1-41 mU/ml, vs. 1 mU/ml, 1-16 mU/ml; P > 0.05). The causes for low erythropoietin levels are not quite understood yet; however, they offer a rationale for the treatment of chronic anemia with recombinant human erythropoietin.
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PMID:Anemia and erythropoietin levels in lung transplant recipients. 852 18

Cellular content of heme is regulated by heme oxygenase, the rate limiting enzyme in the degradation of heme. Induction of heme oxygenase is a protective response in an in vivo model of heme protein mediated renal injury, the glycerol model of acute renal failure. In addition to heme, heme oxygenase is induced by diverse forms of oxidative stress, the functional significance of which is currently unknown. We examined whether heme oxygenase is induced, and the functional significance of such induction, in two in vivo models of oxidant-induced toxic nephropathy, namely, cisplatin and gentamicin nephropathies; nephrotoxicity in these models is not dependent on the delivery of a burden of heme proteins to the kidney as occurs in the glycerol model. We demonstrate induction of heme oxygenase mRNA and protein in the kidney as early as 6 and 12 hours after a single dose of cisplatin (6 mg/kg i.v.). Pretreatment with tin protoporphyrin, a competitive inhibitor of heme oxygenase, led to higher serum creatinine values on days 3 through 5 and lower inulin clearances on day 5; tin protoporphyrin also exacerbated renal injury in this model. Renal hemodynamics studied at day 2 after cisplatin demonstrate reduced renal blood flow rates, increased renal vascular resistance and increased fractional excretion of sodium in rats treated with tin protoporphyrin. Tin protoporphyrin alone had no significant effect on serum creatinine and renal hemodynamics in rats with intact, disease-free kidneys. We confirmed that tin protoporphyrin prevented the increase in heme oxygenase activity induced by cisplatin. Induction of heme oxygenase by cisplatin was associated with increased kidney heme content and ferritin content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of heme oxygenase in toxic renal injury: a protective role in cisplatin nephrotoxicity in the rat. 856 92

Re-establishment of erythropoietin (EPO) secretion following renal transplantation is poorly understood. The development of sensitive EPO radioimmunoassay has enabled further study of this phenomenon. Forty-one adult patients were studied during the first 16 weeks following renal transplantation. Twenty six received cyclosporin monotherapy and 15 also received prednisolone and azathioprine. Serum creatinine, haemoglobin (Hb), ferritin and EPO were assayed pre-operatively, daily for 1 week, weekly for 1 month, and fortnightly to 16 weeks. An expected EPO value, for any Hb level, was derived by linear regression analysis in 144 patients with iron deficiency anemia. An observed to expected ratio (O/E) was calculated, a value of 1.0 implying appropriate responsiveness. Hb increased from 8.6 +/- 2.0 (SD) to 12.3 +/- 2.1 g/dl (p < 0.001) over 16 weeks, an increase unaffected by ferritin status. Mean EPO concentration increased during the first week with a peak at day 4 (22.1 +/- 13.3 to 44.6 +/- 40.0 mu/ml, p < 0.05), a change apparent only in patients with immediate graft function (24 cases). There was no correlation between EPO and Hb pre-operatively; however a significant inverse relationship was established by week 16 (r = -0.404, p < 0.02). The median O/E ratio (0.22) at baseline increased progressively to 1.0 at 16 weeks (p < 0.001); ratios were significantly greater in the immediate versus delayed function group throughout (p < 0.05). In the former group an O/E ratio of 1.0 was reached at 10 weeks when mean serum creatinine was 142 +/- 48 mumol/l. Patients with poor ongoing renal function (9 cases, serum creatinine > 250 mumol/l at 16 weeks) had impaired Hb recovery (10.1 +/- 1.6 vs 12.7 +/- 2.0 g/dl at 16 weeks, p < 0.05). EPO values were not different in those patients but median O/E ratios were significantly depressed (p < 0.05) throughout, the maximum O/E ratio being 0.75. Recovery of renal function is accompanied by a beneficial Hb response driven by EPO synthesis in the transplant. The O/E ratio provides a useful index to assess EPO responsiveness. Appropriate secretion was achieved during the first 4 months and optimized by immediate and satisfactory graft function.
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PMID:Re-establishment of erythropoietin responsiveness in end-stage renal failure following renal transplantation. 898 58

This study evaluated the effect of dietary cadmium (Cd) on atherosclerosis in the rabbit. Cholesterol was added to the diet to initiate and/or accelerate atherogenesis. Cd was added to the diet at two dose levels. Uptake of Cd was 55 micro gram/kg body weight (BW)/day at the low dose level and 1350 micrograms/ kg BW/day at the high dose level. Five groups of rabbits were fed five different diets for 9 months: (1) basal diet without additional constituents; (2) background diet, which was basal diet to which cholesterol had been added; (3) the low-dose level Cd diet, which was background diet to which 2 mg Cd/kg had been added; (4) high-dose level Cd diet, which was background diet to which 50 mg Cd/kg had been added; and (5) basal diet to which 50 mg Cd/kg had been added. Dietary cholesterol increased blood total leucocyte count, serum and liver total cholesterol concentrations, serum total bilirubin concentration, low-density lipoprotein vitamin E concentration and induction of atherosclerotic plaques in the aorta and coronary arteries. Cd in the diet increased liver and kidney Cd concentrations in a dose-dependent way, decreased prothrombin time and temporarily increased urea and creatinine clearances. Slight kidney damage was induced by Cd only in animals fed the high-dose level Cd diet (with or without cholesterol). Dietary Cd partly counteracted the dietary cholesterol-induced increases of serum and liver total cholesterol concentrations, and tended to reduce plaque formation in the aorta. Dietary Cd in rabbits fed cholesterol-containing diets influenced cholesterol metabolism and tended to decrease atherosclerosis in a dose-related fashion. This is in contrast with limited epidemiological human data. Dietary Cd also decreased serum ferritin concentration and increased serum transferrin concentration. Free iron concentration is associated with myocardial infarction in man and augments the development of atherosclerosis in rabbits. It is concluded that the observed reduction in atherogenesis is related to dietary Cd-induced changes in cholesterol metabolism, increased rheology of blood and/or, most likely, reduced free iron concentration.
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PMID:Cadmium and atherosclerosis in the rabbit: reduced atherogenesis by superseding of iron? 876 54

Forty patients with chronic renal failure (CRF) were enrolled into the study, none of whom had peptic ulcer disease, amyloidosis, a previous abdominal operation, diabetes mellitus or other factors that could influence gastric emptying. Twenty of the 40 patients had been receiving regular haemodialysis (HD) for at least 1 year prior to the study. Twelve of the 40 patients had upper gastrointestinal symptoms/signs (GI Sx). Radionuclide-labelled solid meals were used to calculate gastric emptying time (GET). Twenty-five normal volunteers comprised the control group. Of the 40 patients, 35 (88%) had an abnormal GET. The incidence of an abnormal GET in HD and non-HD patients was 95 and 80%, respectively; the incidence of an abnormal GET in patients with and without upper GI Sx was 83 and 89%, respectively. These differences in the incidence of an abnormal GET among the HD and non-HD patients, as well as in the patients with and without upper GI Sx, were not statistically significant. There were no significant differences between the normal and abnormal GET patients for any of the following clinical parameters and conditions: dialyser-specific proportionality constant x time/urea distribution volume (KT/V), protein catabolic rate (PCR), ferritin, serum blood urea nitrogen, creatinine, calcium ion, phosphate, intact parathyroid hormone, albumin, uric acid, haemoglobin, triglyceride and cholesterol, total dialysis time, creatinine clearance and daily urine protein. We conclude that in Chinese patients with CRF, both dialysed and undialysed, an abnormal GET is common. The pathogenesis seems to be multifactorial. The presence of abdominal symptoms cannot foretell an abnormal GET.
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PMID:Delayed gastric emptying in patients with chronic renal failure. 877 42


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