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)

This multicentre study in 142 transfusion-dependent patients with chronic renal failure maintained by haemodialysis was performed to establish the appropriate dose regimen of rHuEpo and define its long-term safety profile. Only one of 132 patients eligible for efficacy analysis did not achieve the haemoglobin target of greater than or equal to 10 g/dl; this particular patient had folate deficiency and overt hyperparathyroidism. Regular blood transfusions were no longer necessary in any patients, however five patients needed blood transfusions only once, not due to rHuEpo failure: two for iron deficiency and three for intercurrent disease. In parallel with the haemoglobin increase a statistically significant improvement in quality of life scores was observed. The weekly dose required to maintain median haemoglobin between 10 and 10.5 g/dl for 1 year (n = 79) was 200-225 U/kg, applied as two or three i.v. injections. Mean serum ferritin decreased from 1900 to 1300 ng/ml and transferrin saturation from 60% to 30%; this feature was associated with statistically significant decrease of pre-study elevated liver enzymes. The treatment had no untoward effect on the outcome of renal transplantation (n = 24). Of the 56 patients who experienced hypertensive episodes during rHuEpo therapy, 47 had a history of hypertension and nine had not. The patient incidence during the first 3 months was 28.9% and fell markedly to 4% after 1 year. Only two hypertensive episodes could not be controlled and the patients dropped out. Seizures occurred in 11 patients, most of them during early treatment; annualised incidence during the first 3 months was 7.78 per year vs 2.07 per year for seizures beyond 3 months treatment. Clinical presentation, patients' history, haemoglobin pattern, BP recordings, brain scan, and EEG indicated that the pathophysiology is multifactorial, with emphasis on rate of haemoglobin increase. Therefore a smooth haemoglobin increase rate, induced by a conservative starting dose regimen (50 U/kg thrice weekly) is recommended, to allow the circulation to adapt to changes in haematocrit/viscosity and O2 delivery. The majority of the observed adverse reactions were related to rHuEpo's therapeutic effect, i.e. increase the haematocrit. The side-effects are therefore largely predictable and can be successfully managed.
Nephrol Dial Transplant 1991
PMID:Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. A European multicentre study in 142 patients to define dose regimen and safety profile. 179 95

Recombinant human erythropoietin (rHuEpo) is an effective therapy for anaemia in most patients with end-stage renal disease (ESRD). However, there remain a minority of patients with ESRD who are resistant to the effects of rHuEpo. The present study examined the role of aluminium overload and hyperparathyroidism of the biological effects of rHuEpo. Twenty-two patients aged 26-74 (mean 53 +/- SD 15.5) received rHuEpo 50-200 U/kg per week for 16.5 +/- 8.0 months (range 3-27). Haemoglobin was maintained at 11.5-13.0 g/dl by appropriate dose adjustment. Iron supplements were provided to maintain serum ferritin greater than 200 ng/ml. The mean time to rHuEpo response (Hb greater than 2 g/dl over baseline) was 6.1 +/- 2.6 weeks. Mean pretreatment serum aluminium correlated with time to Hb response (r = 0.48; P less than 0.05) and pretreatment mean corpuscular volume (r = 0.43; P less than 0.05) but not with eventual rHuEpo maintenance dose. PTH did not correlate with either Hb response or eventual maintenance rHuEpo dose. In summary, elevated serum aluminium concentrations were associated with an initial resistance to the biological effects of rHuEpo but had no effect on long-term dose requirements. In contrast, no impact of PTH on either immediate or long-term rHuEpo dose was evident.
Nephrol Dial Transplant 1991
PMID:The role of aluminium and parathyroid hormone in erythropoietin resistance in haemodialysis patients. 187 Jul 50

The incidence of bacteraemia in relation to the degree of transfusional iron overload was studied prospectively in patients from one haemodialysis unit over a 2-year period, with a total follow-up of 181.3 patient-years in 158 patients. Every 3 months, the patients were classified according to the serum ferritin in one of three groups: less than 500, 500-1000 or greater than 1000 micrograms/l. Twenty-nine episodes of bacteraemia were recorded over 181.3 patient-years (yearly incidence of 0.160). The yearly incidence of bacteraemia was 0.1173 and 0.1101 for ferritin less than 500 and 500-1000 micrograms/l (no significant difference), with a cumulative incidence for both groups of 0.1164. In the ferritin greater than 1000 micrograms/l group, the incidence was 0.3404 (P less than or equal to 0.005 versus the ferritin less than or equal to 1000 micrograms/l group). After stratification for patient's age (at inclusion in the study) and duration of haemodialysis therapy, the higher incidence of bacteraemia in the ferritin greater than 1000 versus less than or equal to 1000 micrograms/l groups persisted (P less than or equal to 0.005). This prospective study confirms previous retrospective studies in showing that acquired transfusional iron overload in haemodialysis is associated with a greater risk of bacteraemia.
Nephrol Dial Transplant 1990
PMID:Iron overload in haemodialysis patients increases the risk of bacteraemia: a prospective study. 211 11

In nine chronic haemodialysis patients a desferrioxamine (DFO) load test (40 mg/kg body-weight) was performed 1 year after the beginning of treatment with recombinant human erythropoietin (rHuEpo). The patients were then divided into two groups. Group A comprised five patients with a greater mean aluminium (204 +/- 28 micrograms/l) than the four patients in group B. Group A was given a mean dose of 25.8 g (range 14-39 g) of DFO over 6 months. Group B (aluminium values 112 +/- 36 micrograms/l) was never treated with DFO. During the period of observation, plasma iron, serum ferritin and transferrin, as well as iron supplementation, did not differ between the groups. After DFO treatment a second DFO load test was performed. The mean predialysis aluminium value was significantly reduced in group A (204 +/- 28 vs 111 +/- 72 micrograms/l; P less than 0.05), while remaining unchanged in group B (112 +/- 36 vs 140 +/- 39 micrograms/l; P = ns). In both groups, the doses of rHuEpo necessary to maintain the same haemoglobin values decreased with time, but reduced significantly only in group A (298 +/- 105 vs 110 +/- 61 mu/kg per week; delta -63%; P less than 0.01). Thus, aluminium interferes with the response to rHuEpo in haemodialysis patients, and the correction of aluminium overload with DFO can allow a considerable sparing of rHuEpo.
Nephrol Dial Transplant 1990
PMID:Aluminium interference in the treatment of haemodialysis patients with recombinant human erythropoietin. 212 21

Iron overload increases the risk of bacterial infection in dialysis patients, partly by impairing functions of the polymorphonuclear granulocytes (PMNs). PMN defence was studied sequentially in haemodialysis patients with transfusional haemosiderosis, treated for 6 +/- 1.5 months (n = 8) to 13 +/- 1.7 months (n = 4) with recombinant human erythropoietin (rHuEpo). Over this period, signs of iron overload (increased serum ferritin and serum iron) improved, and stainable iron disappeared in PMNs. Simultaneously, phagocytosis of Yersinia enterocolitica by PMNs improved. The decrease in serum ferritin was significantly related to the improved phagocytosis. Killing of Y. enterocolitica by PMNs also improved. It is anticipated that rHuEpo therapy in iron-overloaded dialysis patients could decrease the incidence of bacterial infection by improving PMN functions in these patients.
Nephrol Dial Transplant 1990
PMID:Recombinant erythropoietin reverses polymorphonuclear granulocyte dysfunction in iron-overloaded dialysis patients. 213 Feb 96

The authors studied the in vitro permeability of different fragments of the rabbit's peritoneum to urea, inulin, horseradish peroxidase, and ferritin. Parietal peritoneum has a lower permeability to middle and large molecules than visceral peritoneum. In addition the local anesthetic, bupivacaine had a different effect on the mesothelial permeability of visceral peritoneum than on that of parietal peritoneum.
Perit Dial Int 1989
PMID:Permeability of different parts of the peritoneal mesothelium to solutes: an in vitro study. 248

Iron overload, which is a common complication in haemodialysis patients, is known to enhance bacterial growth and virulence, and to alter phagocytosis. We reviewed the data of 61 haemodialysed patients to clarify the clinical relevance of iron status to the risk of bacterial infection. Increased concentrations of serum ferritin were associated with a greater infection rate (P less than 0.0025), which was already true for ferritin values between 500 and 1000 micrograms/l (P less than 0.025). Furthermore, in 21 iron-overloaded patients treated with an iron-chelator (desferrioxamine), the infection rate decreased from 1/19 patient-months to 1/112 (P less than 0.005), and returned to previous values when desferrioxamine was stopped. Our results demonstrate the importance of haemosiderosis in the increased susceptibility of haemodialysed patients to infections; this susceptibility is decreased by desferrioxamine therapy, which probably acts by restoring phagocytosis and reducing the bioavailability of iron for pathogens.
Nephrol Dial Transplant 1989
PMID:Critical role of iron overload in the increased susceptibility of haemodialysis patients to bacterial infections. Beneficial effects of desferrioxamine. 251 93

Recombinant human erythropoietin (R-Hu-EPO) was given to stable, long-term haemodialysis patients with haematocrit less than or equal to 25% who required no blood transfusions. Thirteen patients were initially given R-Hu-EPO at 24 U/kg i.v. at the end of each dialysis session, with a doubling of the dose every second week until a dose of 96 U/kg (n = 6) or 192 U/kg (n = 7) was reached after 8 weeks. In addition, three patients were given 24 U/kg for 2 weeks and subsequently 48 U/kg for 14 weeks. Median haematocrit increased from 19.4% (14.8-24.3) to 30.0% and 32.5% with 96 or 192 U/kg respectively. Starting 7 days after R-Hu-EPO a log dose-dependent increase in reticulocyte counts was noted. A consistent decrease in ferritin concentrations was observed despite oral supplementation of iron. A continuous rise in platelet counts was noted. Irrespective of blood-pressure status, predialysis blood pressure increased in six of nine patients who were not on antihypertensive medication; increased antihypertensive therapy was required in the others. A rise in bilirubin within the normal range was seen at the end of the study. No severe clinical side-effects occurred; specifically, there were no thrombotic episodes with the exception of clotting of two fistulae with known stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1987
PMID:Recombinant human erythropoietin therapy in haemodialysis patients--dose determination and clinical experience. 311 64

We have prospectively investigated the effect of desferrioxamine (DFO) administration (2 gi.v. after every haemodialysis session for 6 months) on the normocytic and normochromic anaemia of seven haemodialysis patients. None had either clinical or analytical data characteristic of chronic aluminium intoxication. At the end of DFO therapy, the haematocrit had increased from 20.5 +/- 2.7% to 30.4 +/- 7.7% (P less than 0.005), and the transfusional requirements decreased from 3.5 +/- 2.2 units (range 1-8 units) in the 6 months prior to DFO, to 0.7 +/- 0.9 units (range 0-2 units) during DFO administration (P less than 0.01). No transfusion was required during the second half of the DFO therapy period. Serum ferritin decreased from 105g +/- 532 nmol/l (2649 +/- 1331 ng/ml) to 507 +/- 403 nmol/l (1268 +/- 1008 ng/ml) (P less than 0.025). Two months after DFO withdrawal the haematocrit value fell significantly to 22.2 +/- 1.6% (P less than 0.01). DFO therapy was restarted in one patient at a lower dose (1 gi.v. after every haemodialysis session) and an increase of haematocrit from 23.8% to 40.2% was again observed after 3 months of treatment. The tolerance to DFO was excellent. We conclude that DFO therapy should be considered in haemodialysis patients with severe anaemia and increased blood transfusion requirements.
Nephrol Dial Transplant 1987
PMID:Improvement of anaemia with desferrioxamine in haemodialysis patients. 311 65

This study clarifies the correlation between guanidino compounds and other laboratory findings including peroxidative markers in the sera of patients undergoing regular haemodialysis. The concentration of guanidine, for example, correlates significantly with iron, ferritin, and malondialdehyde. Guanidine is synthesized from various guanidino compounds such as arginine, guanidinoacetic acid, creatinine, creatine, methylguanidine, guanidinosuccinic acid, and canavanine in vitro by the hydroxyl radical. These results suggest that guanidine is synthesized as a result of active oxygen, and demonstrates the importance of guanidine as an indicator of the peroxidative state in patients with uraemia.
Nephrol Dial Transplant 1988
PMID:Evidence for the role of active oxygen in guanidine synthesis in haemodialysis patients and in vitro. 314 21


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