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Query: UMLS:C0240066 (iron deficiency)
 7,156 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

Administration of recombinant human erythropoietin (r-HuEPO) in uraemic pre-dialysis patients is both effective and safe. The benefits are similar to those in dialysis patients: a marked increase in subjective wellbeing and ability to perform physical work. There is a strong argument for treating on the basis of anaemic symptoms, rather than on absolute haematocrit or haemoglobin. Some 30-40% of r-HuEPO-treated pre-dialysis patients may need initiation of, or an increase in, antihypertensive therapy. Provided blood pressure is carefully controlled, r-HuEPO does not appear to accelerate the progression of renal failure, and there is preliminary evidence that it may even delay the need for dialysis in children and possibly in adults. Subcutaneous self-administration is convenient for most pre-dialysis patients; once weekly administration can yield effective results and may enhance patient compliance. As in dialysis patients, detection and correction of iron deficiency play an essential role in maximizing the success of r-HuEPO administration. For most pre-dialysis patients, oral iron administration is convenient, and absorption is satisfactory.
Nephrol Dial Transplant 1995
PMID:Starting r-HuEPO in chronic renal failure: when, why, and how? 764 5

The most common cause of limited response to recombinant human erythropoietin (r-HuEPO) is unrecognized, mild-to-moderate iron deficiency, either at the start of treatment or secondary to enhanced iron utilization by newly formed erythrocytes. Iron stores in patients with chronic renal failure (CRF) are often depleted through gastrointestinal bleeding, blood loss during haemodialysis, and blood sampling. Mobilization of iron stores may be inadequate, especially during rapid haemoglobin regeneration. Aluminium overload may also interfere with gastrointestinal and cellular iron uptake. Overt or unrecognized infection or inflammation is another common cause of hyporesponsiveness, and is a consequence of increased blood concentrations of cytokines such as tumour necrosis factor (TNF), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma), which suppress erythrocyte stem-cell proliferation. Less common causes include severe secondary hyperparathyroidism and myeloma (during chemotherapy). Response to r-HuEPO can be best predicted by baseline fibrinogen (a marker of subclinical inflammation); baseline transferrin receptor (sTfR) concentrations (a marker of functional iron deficiency); and sTfR increment after 2 weeks (a marker of early change in erythropoietic activity).
Nephrol Dial Transplant 1995
PMID:R-HuEPO hyporesponsiveness--who and why? 764 9

Inadequate iron supply is probably the most common and most easily treated cause of sub-optimal response to recombinant human erythropoietin (r-HuEPO). A low ferritin value is a reliable indicator of iron deficiency, provided that patients are in equilibrium (e.g. without infection, bleeding, vitamin or folate deficiency). Normal or high ferritin values do not necessarily preclude iron deficiency. Transferrin saturation is not always a reliable indicator of iron deficiency. The measure which best reflects iron supply to the erythron is the percentage of hypochromic red cells. Iron supplementation should be targeted at keeping serum ferritin > 100 micrograms/l, transferrin saturation > 20%, and hypochromic red cells < 10%. Iron status should be monitored monthly for the first few months after initiation of r-HuEPO, and thereafter at 2-3 month intervals. For haemodialysis patients, who have a very high rate of iron loss, i.v. iron administration is preferable and may also be appropriate for patients on continuous ambulatory haemodialysis (CAPD) and pre-dialysis patients. Recent studies with i.v. iron supplementation have shown no difference between the s.c. and i.v. routes of administration of r-HuEPO. Both the i.v. and the s.c. route are appropriate for patients on haemodialysis, whereas patients on CAPD or pre-dialysis patients should receive s.c. r-HuEPO. The optimum frequency of s.c. administration in the vast majority of patients is 2-3 times weekly. For a small number of patients, once weekly s.c. administration may be suitable. When satisfactory haemoglobin values are reached, the dose of r-HuEPO should be titrated down gradually. It should not be stopped abruptly unless there are life-threatening complications.
Nephrol Dial Transplant 1995
PMID:How to get the best out of r-HuEPO. 764 13

Various studies have shown that peritoneal dialysis patients may require less erythropoietin (rHuEPO) than maintenance hemodialysis patients. Iron deficiency in hemodialysis patients may contribute to the difference in response. This study compares the response to rHuEPO in 24 patients on CAPD to 33 patients on hemodialysis. All the hemodialysis patients received intravenous iron to prevent iron deficiency. Peritoneal dialysis patients received rHuEPO subcutaneously twice weekly. Erythropoietin was administered intravenously thrice weekly in hemodialysis patients. In peritoneal dialysis patients, hematocrit was 23.1% and 30.1%, rHuEPO dose was 80.9 and 89.0 u/kg/wk, while in hemodialysis patients hematocrit was 22.2% and 31.2%, and rHuEPO dosage was 140.2 and 154.3 u/kg/wk at initiation, and six months after therapy (p < 0.05 for dose, hemodialysis vs CAPD). Serum iron and transferrin saturation remained normal both in peritoneal and hemodialysis patients. These findings suggest that hemodialysis patients require a higher dosage of rHuEPO than peritoneal dialysis patients for a comparable rise in hematocrit, even when iron deficiency is prevented with parenteral iron. The improved efficacy of rHuEPO in CAPD patients may be due to the better removal of the inhibitors of erythropoiesis and/or the subcutaneous route of administration.
Adv Perit Dial 1994
PMID:Improved response to erythropoietin in peritoneal dialysis patients as compared to hemodialysis patients: role of iron deficiency. 799 11

Three patients on chronic maintenance haemodialysis have progressively increased their haematocrit to reach values between 40 and 45%, a situation associated with an increased risk of thrombosis of their arteriovenous fistulae. Two of them had been submitted to repeated phlebotomies, which remained unsuccessful despite the induction of a profound iron deficiency in one of them. Hence, a trial with oral theophylline was performed in the three patients, resulting in a sustained decrease of the haematocrit (from 43.6 to 33%) and endogenous erythropoietin (from 46 to 15 mU/ml) levels. In two patients, theophylline therapy was stopped transiently due to gastrointestinal side-effects, which resulted in a rapid return to previous haematocrit levels; rechallenge with a better tolerated preparation, however, was efficient again. We conclude that oral theophylline appears to be an efficient treatment to control too high haematocrit levels in dialysis patients.
Nephrol Dial Transplant 1994
PMID:High haematocrit in haemodialysis patients can be controlled by theophylline administration. 786 12

Haemodialysis patients with iron overload sometimes develop resistance to erythropoietin therapy due to 'functional iron deficiency'. It is known that this resistance may be overcome by iron supplementation; however, the latter could worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis patients who had developed relative resistance to erythropoietin (among whom three had features of 'functional iron deficiency') with ascorbic acid (500 mg intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses were voluntarily kept unchanged during the study. After a latency of 2-4 weeks, haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7 +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P < 0.001). While serum ferritin remained unchanged, transferrin saturation increased from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that ascorbic acid supplementation had allowed mobilization of iron from tissue burdens. In one patient, haematocrit declined after withdrawal of vitamin C and increased again after rechallenge. Also, ascorbate supplementation was continued after the study in two patients and allowed the erythropoietin doses to be decreased, 8 and 11 weeks, respectively, after the start of the trial. When a control group of seven patients with normal iron status and without resistance to erythropoietin were challenged in the same manner with ascorbate, no elevation of haematocrit or transferrin saturation was noted. We conclude that ascorbate supplementation may circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded patients, in particular, in the setting of 'functional iron deficiency'.
Nephrol Dial Transplant 1995
PMID:Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by ascorbic acid administration. 852 94

Some chronic renal failure patients respond poorly to recombinant human erythropoietin (rHuEPO). In continuous ambulatory peritoneal dialysis (CAPD) patients, such a poor response may indicate inadequate dialysis or low body iron stores. To correct iron deficiency, once-a-week intravenous iron supplementation is recommended. However, hemodialysis patients receive iron supplements three times a week. This study was designed to compare the efficacy of iron supplementation between once-weekly and twice-weekly regimens. In both groups, rHuEPO doses were similar. Seventeen CAPD patients were studied. All had hemoglobin levels less than 10 g/dL. Ten patients were given 100 mg intravenous iron once weekly, and 7 were given 50 mg intravenous iron twice weekly until a total iron dose of 600 mg was achieved (stage I). The patients were crossed over to receive another 600 mg iron (stage II). Hematocrit increased significantly in patients receiving twice-a-week iron supplementation (+3.8% and 6%) compared to those receiving once-a-week iron supplementation (+1.3% and 1.4%) during stages I and II. The ferritin levels were not different between the groups. In conclusion, rHuEPO is more effective when administered with intravenous iron.
Adv Perit Dial 1997
PMID:The efficiency of fractionated parenteral iron treatment in CAPD patients. 936 Jun 61

The need for a renewable source of erythropoietin to treat the anaemia of chronic renal failure was first recognized in the 1960s, but cloning and expression of the human gene was not achieved until 1983. Clinical testing of recombinant human erythropoietin (r-HuEPO) began in 1985, leading to the first licence as a therapeutic agent in 1988. The first clinical trials showed that an intravenous dose requirement of about 200 IU/kg/week would increase haemoglobin concentrations to 10-12g/dl in >90% of haemodialysis patients. Subcutaneous administration has subsequently been found to be effective, and may allow lower maintenance doses. It is now the route of choice in Europe, but not the USA. The best marker of benefit of the introduction of r-HuEPO is the reduction in need for regular blood transfusions. A marked improvement in anaemia-related symptoms has been clearly demonstrated. The most important factor in optimizing the response to r-HuEPO is iron supply. The marrow should be stimulated slowly, to allow mobilization of iron stores. Functional or absolute iron deficiency should be pre-empted by regular iron supplementation. It is also important to recognize resistant states induced by inflammation and bleeding, and to exclude severe hyperparathyroidism, aluminium overload and other haematological diseases. The most important adverse events associated with r-HuEPO are increased blood pressure and a possible increased risk of access failure. These are, however, challenges to improve practice, not reasons to avoid the use of r-HuEPO.
Nephrol Dial Transplant 1998
PMID:Recombinant human erythropoietin: 10 years of clinical experience. 956 83

A number of factors have been shown to limit the response to recombinant human erythropoietin (r-HuEPO). One major factor appears to be an inadequate iron supply to the bone marrow. Erythropoiesis is dependent upon a continuous supply of iron to the bone marrow. The rate at which iron can be drawn from existing stores may easily limit the rate of delivery for haemoglobin synthesis. This results in 'functional iron deficiency' which is distinct from 'absolute iron deficiency' caused by depletion of iron stores. At present there are three main parameters available to clinicians wishing to monitor iron status in their patients: serum ferritin and transferrin saturation (TFS), which are indirect measurements, and the percentage of hypochromic red cells, which directly reflects marrow iron status. Ferritin levels should be measured before starting r-HuEPO therapy to ensure adequate iron stores (>200 microg/l), and when patients move from the correction phase to the maintenance phase of therapy (have stores become depleted during the correction phase?). In addition, ferritin levels can give an indication of iron overload following excess parenteral iron administration. The TFS represents a balance between iron supply by stores and demand by bone marrow. A saturation below 20% probably indicates iron-deficient erythropoiesis. However, this is an indirect measure of marrow iron supply and wide fluctuations have been observed when determined at different time points. The percentage of hypochromic red blood cells is measured by flow cytometry and a hypochromic subpopulation of more than 10% (normal percentage <2.5%) indicates iron-deficient erythropoiesis. However, not all departments may have access to the required equipment. The aim of iron supplementation is to provide sufficient iron for the correction phase and to replace iron losses (1500-2000 mg/year in haemodialysis patients) during the maintenance phase of r-HuEPO therapy. This amounts to a daily iron need in the range of 5 7 mg, which is well above the normal dietary intake and absorptive capacity of the human intestine. Therefore, there is a need for intravenous iron, in particular when the patient has absolute or functional iron deficiency, is intolerant of oral iron, or is not complying well with the oral regimen.
Nephrol Dial Transplant 1998
PMID:Iron monitoring and supplementation: how do we achieve the best results? 956 84


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