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)

Two previous short-term studies (12 weeks and up to 16 weeks) that used androgens to supplement recombinant human erythropoietin (rHuEPO) for the treatment of the anemia associated with end-stage renal disease showed divergent results. Both studies were limited by their brief duration, since the hematopoietic effect of androgens does not peak until 5 months. Therefore, we conducted a 6-month, prospective, randomized trial comparing low-dose rHuEPO alone and in combination with androgens for the treatment of the anemia of end-stage renal failure. Nineteen anemic chronic hemodialysis patients were randomized into two groups. Group A (n = 10) received 1,500 U rHuEPO intravenously three times a week for 26 weeks. Group B (n = 9) received the same dose of rHuEPO plus nandrolone decanoate 100 mg intramuscularly weekly. Baseline transferrin saturation, serum ferritin, intact serum parathyroid hormone, plasma aluminum, and hematocrit levels were not significantly different between the groups. At study completion, both groups showed a significant increase in mean hematocrit compared with baseline (group A: 24.8% +/- 1.4% to 28.3% +/- 2.8%, P = 0.003; group B: 25.1% +/- 1.5% to 33.2% +/- 4.5%, P = 0.001). The increase in hematocrit in the rHuEPO plus androgen-treated group was statistically greater than in the rHuEPO-alone group (8.2% +/- 4.4% v 3.5% +/- 2.8%; P = 0.012). With the exception of mild discomfort at the injection site, there were no significant side effects from nandrolone. We conclude that the combination of low-dose rHuEPO and nandrolone decanoate is effective treatment for the anemia of end-stage renal failure.
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PMID:A 6-month study of low-dose recombinant human erythropoietin alone and in combination with androgens for the treatment of anemia in chronic hemodialysis patients. 932 63

In cases with severe hyperparathyroidism, anaemia improves after parathyroidectomy. The objective of this study was to investigate the influence of treatment with intravenous calcitriol on anaemia in 28 haemodialysis patients. The patients showed moderate to severe hyperparathyroidism (mean parathyroid hormone level 811.6 +/- 327 pg/ml) and were treated with calcitriol (2 microg i.v.) after haemodialysis. The follow-up period was 12 months. 21 out of the 28 patients had been receiving erythropoietin (EPO) prior to calcitriol administration; the remaining 7 did not receive EPO. 24 patients received oral or intravenous iron. The doses of EPO and iron were modified throughout the study period to maintain a haematocrit equal to or higher than 30% and ferritin levels above 150 ng/ml, respectively. EPO needs were evaluated according to the relation EPO dose/haematocrit. We found a significant rise in haematocrit and haemoglobin at 3 and 12 months on calcitriol therapy, with no modification of the EPO dose nor ferritin levels. This improvement in anaemia was observed both in those patients who received EPO initially (p < 0.01) and in those who did not (p < 0.05). Upon dividing the patients according to the response of hyperparathyroidism to the intravenous calcitriol treatment, we observed in the responding patients (n = 19) significant increases in haematocrit (from 31.7 +/- 4.2 to 36.3 +/- 4.9%) and haemoglobin(from 10.6 +/- 1.5 to 12.2 +/- 1.5 g/dl; p < 0.001) at 12 months on intravenous calcitriol therapy, while this was not true of the non-responding patients. The EPO needs diminished in the group of responding patients and increased in the non-responders, although these changes were not statistically significant. We found no direct correlation between the decrease of parathyroid hormone and EPO needs in the group of responding patients. However, an inverse correlation between parathyroid hormone levels and EPO needs (r = -0.799, p < 0.05) was seen in the group of non-responding patients. Treatment with intravenous calcitriol in patients on haemodialysis controls secondary hyperparathyroidism, improves anaemia, and decreases the need for EPO. Studies including a larger number of patients are necessary to clarify the mechanisms underlying the improvement of anaemia upon control of secondary hyperparathyroidism with intravenous calcitriol treatment and to confirm our findings.
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PMID:Intravenous calcitriol improves anaemia and reduces the need for erythropoietin in haemodialysis patients. 945 99

The restless legs syndrome (RLS) is one of the most common and unpleasant complaints of uremic patients. The pathophysiology of the RLS is still unclear. Various factors, including anemia and iron deficiency, are proposed to play a major role. We determined the prevalence of RLS in all stable hemodialysis patients under long-term treatment in two dialysis centers (n = 136) and compared the clinical and biochemical findings of patients with RLS and without RLS. Twenty-three percent of all patients investigated fulfilled the diagnostic criteria of RLS according to the International Restless Legs Syndrome Study Group. There were no statistical differences between the two groups regarding age, duration of uremia and need for dialysis, time on dialysis per week, hemoglobin, hematocrit, erythrocytes, s-ferritin, s-transferrin, s-iron, calcium, and standard biochemical indices, except for intact parathyroid hormone (iPTH) levels. Uremic patients with RLS showed significantly lower iPTH (P < 0.01) concentrations. In addition, the RLS group received a significantly higher number and dosage of psychopharmacological drugs, (ie, L-DOPA), than patients without RLS. These biochemical findings suggest that neither the severity of anemia nor that of iron deficiency has to be considered a major pathophysiological factor in established RLS. The significantly lower iPTH secretion in uremic patients with RLS, however, is a new finding, and further investigations will be necessary to determine whether this result is of any clinical significance to this group of patients. The significantly higher number of psychopharmacological drugs prescribed to uremic patients with RLS may be related to the symptoms of RLS.
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PMID:Clinical and biochemical findings in uremic patients with and without restless legs syndrome. 946 5

The present study was designed to investigate the impact of aluminum toxicity on the response to recombinant human erythropoietin (rHuEPO) therapy in hemodialysis patients, when iron deficiency has been corrected or excluded. We studied 39 patients on regular hemodialysis (20 males and 19 females; mean age 58.8 years), who were under maintenance rHuEPO treatment for at least 6 months, and who had stable hematocrit levels for more than 3 months. All patients had adequate iron stores and availability with serum ferritin > 100 micrograms and iron saturation > 25%. They were classified into two groups: 19 poor responders, who required subcutaneous rHuEPO doses > 100 U/kg/week and failed to achieve the target hematocrit level of 30%, and 20 good responders, who needed doses of < or = 100 U/kg/week to maintain the target level. Serum aluminum levels including basal (Albasal) and 44 h after desferrioxamine (DFO) infusion (Alpost-DFO), intact parathyroid hormone, and inflammatory and hemolytic indices were examined in both groups. The results showed that the mean weekly rHuEPO doses were significantly lower and the mean hematocrit levels higher in the good responders than in the poor responders. Although the poor responders had markedly higher mean Albasal and Alpost-DFO levels, no differences were observed in the other parameters between the two groups. Furthermore, the poor responders significantly had the greater increment in the serum aluminum levels after DFO infusion (delta Al = Alpost-DFO-Albasal). The mean corpuscular volume had a strong inverse correlation with delta Al in the poor response group (r = -0.711, p < 0.001). We concluded that the post-DFO rise of serum aluminum can be used as a means of estimating tissue stores. Subclinical aluminum toxicity may exhibit an inhibitory effect on erythropoietic response to rHuEPO therapy.
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PMID:Recombinant human erythropoietin resistance in iron-replete hemodialysis patients: role of aluminum toxicity. 948 32

The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice weekly, was studied prospectively in 17 children and adolescents with end-stage renal disease who were either transfusion dependent or had hematocrits < 25%. For convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure, hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored serially. When serum ferritin was < 100 ng/ ml during therapy, 6 patients received iron supplementation. rHuEPO therapy eliminated frequent transfusions in all patients; 11 of 17 patients reached the target hematocrit of 30%-33% by week 16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously reached target at week 6 +/- 1; 6 HD patients treated intravenously reached target at week 11 +/- 3; 6 additional HD patients never reached target at this dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher than those of the other patients (P < 0.005); 3 of 6 later reached a hematocrit of 30%-33% after the rHuEPO dose was increased to 120-130 units/kg thrice weekly. We conclude that most pediatric dialysis patients can be treated successfully with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is markedly elevated, in which case a higher dose is likely to be needed.
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PMID:Effect of hyperparathyroidism on response to erythropoietin in children on dialysis. 965 62

In 1990 Scopinaro's technique of biliopancreatic diversion with distal gastrectomy (DG) and gastroileostomy was modified. A sleeve gastrectomy with duodenal switch (DS) was used instead of the distal gastrectomy; and the length of the common channel was made 100 cm instead of 50 cm. A questionnaire and a prescription for blood work were sent to 252 patients who underwent DG a mean 8.3 years ago (range 6-13 years) and 465 patients who underwent DS 4.1 years ago (range 1.7-6.0 years). The questionnaire response rate was 93%, and laboratory work was completed for 65% of both groups. The mean weight loss after DG was 37 +/- 21 kg and after DS 46 +/- 20 kg. There were fewer side effects after DS: The number of daily stools was lower (p < 0.0002), as was the prevalence of diarrhea (p < 0.01), vomiting (p < 0.001), and bone pain (p < 0.001). Greater benefits related to several aspects of life were reported after DS than DG (p < 0.0001). The mean serum levels of ferritin, calcium, and vitamin A were higher (p < 0.001), and parathyroid hormone was lower. The yearly revision rate for excessive malabsorption was 1.7% per year after DG and 0.1% per year after DS. The two procedures were equally efficient for treating co-morbid conditions such as diabetes, hypertension, and hypercholesterolemia. Biliopancreatic diversion with sleeve gastrectomy/duodenal switch and a 100-cm common limb was shown to produce greater weight loss with fewer side effects.
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PMID:Biliopancreatic diversion with duodenal switch. 971 20

To define which noninvasive investigations are of value in predicting bone histology, we analyzed transiliac bone specimens (66 biopsies, 14 autopsies) from 80 uremic patients on chronic dialysis. Results were compared with values of different measurements of parathyroid hormone (PTH), alkaline phosphatase (APH), osteocalcin, calcitonin, baseline and post-deferroxamine (DFO) aluminium (Al),--beta 2 microglobulin, ferritin and bone mineral density. Among histomorphometric parameters, woven osteoid, active osteoblastic surface and resorption surface showed the best correlations with dynamic and biochemical marks of active bone metabolism. Among biochemical parameters, intact PTH and APH were better related to histomorphometric and dynamic bone parameters than other PTH measurements as well as osteocalcin, while calcitonin was related to no parameters. Stainable Al alone, and not total bone Al content was related to bone histology. Baseline Al was related to lamellar osteoid, while post-DFO Al was related to stainable Al. beta 2 microglobulin was positively related to active osteoid surface and ferritin was inversely related to the mineral apposition rate, while bone mineral density was related only to total bone volume. We conclude that, though definite diagnosis requires the use of histological methods, few simple biochemical parameters may offer insight to the bone metabolic status, useful to the physician in day to day clinical practice.
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PMID:Correlations between bone histopathology and serum biochemistry in uremic patients on chronic hemodialysis. 980 45

Insulin and lipid metabolism were studied in seven patients (19+/-1 years) with end-stage renal disease on continuous cycling peritoneal dialysis (CCPD) before and after 6 months of therapy with human recombinant erythropoietin (EPO) to correct anemia. Hematocrit increased from 22.2+/-1.8% to 34.8+/-1.8% (P<0.001) following EPO treatment. Serum ferritin (P<0.05) and serum iron (P<0.01) decreased significantly after anemia correction. There were no significant differences in the height, weight, anthropometric measures, or intakes of protein and total calories in the patients before and after the 6 months of EPO therapy. There were no differences in serum biochemical parameters, including 1,25-dihydroxyvitamin D3 and parathyroid hormone in these patients before and after 6 months of EPO therapy. Residual renal function and Kt/Vurea were also not different before and after 6 months of EPO therapy. The hyperinsulinemic euglycemic clamp technique was used to measure insulin sensitivity. Before EPO, insulin sensitivity was low in patients on CCPD (238+/-19 mg/m2 per min) compared with controls (320+/-30; P<0.01). After 6 months of EPO therapy, insulin sensitivity increased by 28% (305+/-26, P<0.01 vs. pre-EPO values), so that these values were no longer different from control values. The hyperglycemic clamp technique was used to measure insulin secretion. Before EPO, both early- and late-phase insulin secretion were elevated in patients on CCPD compared with controls (P<0.01 in both cases). These indices of insulin secretion decreased significantly (P<0.01) following 6 months of EPO. Before EPO, plasma triglycerides, total cholesterol, low-density lipoprotein, cholesterol, and apolipoprotein B were elevated in patients compared with controls. These lipid concentrations decreased significantly following 6 months of EPO. Thus, treatment of anemia by EPO is associated with improvements in insulin and lipid abnormalities in uremic patients on CCPD.
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PMID:Metabolic effects of erythropoietin in patients on peritoneal dialysis. 981 91

We defined erythropoietin (EPO) resistance by the ratio of the weekly EPO dose to hematocrit (Hct), yielding a continuously distributed variable (EPO/Hct). EPO resistance is usually attributed to iron or vitamin deficiency, hyperparathyroidism, aluminum toxicity, or inflammation. Activation of the acute-phase response, assessed by the level of the acute-phase C-reactive protein (CRP), correlates strongly with hypoalbuminemia and mortality in both hemodialysis (HD) and peritoneal dialysis (PD) patients. In this cross-sectional study of 92 HD and 36 PD patients, we examined the contribution of parathyroid hormone (PTH) levels, iron indices, aluminum levels, nutritional parameters (normalized protein catabolic rate [PCRn]), dialysis adequacy (Kt/V), and CRP to EPO/Hct. Albumin level serves as a measure of both nutrition and inflammation and was used as another independent variable. Serum albumin level (deltaR2 = 0.129; P < 0.001) and age (deltaR2 = 0.040; P = 0.040) were the best predictors of EPO/Hct in HD patients, and serum albumin (deltaR2 = 0.205; P = 0.002) and ferritin levels (deltaR2 = 0.132; P = 0.015) in PD patients. When albumin was excluded from the analysis, the best predictors of EPO/Hct were CRP (deltaR2 = 0.105; P = 0.003) and ferritin levels (deltaR2 = 0.051; P = 0.023) in HD patients and CRP level (deltaR2 = 0.141; P = 0.024) in PD patients. When both albumin and CRP were excluded from analysis in HD patients, low transferrin levels predicted high EPO/Hct (deltaR2 = 0.070; P = 0.011). EPO/Hct was independent of PTH and aluminum levels, PCRn, and Kt/V. High EPO/Hct occurred in the context of high ferritin and low transferrin levels, the pattern expected in the acute-phase response, not in iron deficiency. In well-dialyzed patients who were iron replete, the acute-phase response was the most important predictor of EPO resistance.
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PMID:Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal dialysis patients. 991 69

Data for iron-status indices in continuous ambulatory peritoneal dialysis patients are limited. The reliability of commonly used indices for the diagnosis of iron-deficiency anemia in peritoneal dialysis patients is still unknown. To study diagnostic values of iron-status indices, including serum ferritin, transferrin saturation, reticulocyte hemoglobin content, and bone marrow-stainable iron, 21 stable anemic peritoneal dialysis patients who have been treated with erythropoietin and oral iron supplementation for more than 3 months were enrolled in this study. The mean age was 51.4 +/- 2.9 years; dialysis duration, 28.7 +/- 5.1 months; initial hemoglobin, 8.4 +/- 0.2 g/dL; erythropoietin dosage, 71 +/- 2 micro/kg/wk; serum albumin, 3.5 +/- 0.1 g/dL; intact parathyroid hormone (PTH), 233 +/- 44 ng/mL; serum ferritin, 643 +/- 135 ng/mL; transferrin saturation, 33.93% +/- 3.9%; and reticulocyte hemoglobin content, 31.6 +/- 4 pg. Bone marrow aspiration was performed in all patients to determine marrow iron content and exclude hematological disorders. All patients were treated with 1, 000 mg of intravenous ferric saccharate infusion in two divided doses more than 1 week apart. Patients who responded to the iron infusion within 3 months by increasing serum hemoglobin of greater than 1 gm/dL more than baseline were defined as being functional iron deficient before the intravenous iron infusion. Serum ferritin, transferrin saturation, and reticulocyte hemoglobin content were followed serially after iron infusion. Fifteen patients (71.4%) responded to the iron administration, indicating iron deficiency. Nine of 13 (69%) patients with the presence of bone marrow-stainable iron still responded to intravenous iron supplementation, suggesting functional iron deficiency. Absence of bone marrow-stainable iron was not a sensitive marker for the diagnosis of iron deficiency, 25% sensitivity. No single value of iron-status indices that can definitely exclude iron-deficiency anemia in peritoneal dialysis patients was found. Therefore, failure to increase hemoglobin concentration after intravenous iron administration should be shown before excluding iron-deficiency anemia as a cause of poor erythropoietic response to erythropoietin therapy.
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PMID:Indices of iron status in continuous ambulatory peritoneal dialysis patients. 1040 Oct 35


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