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Query: UMLS:C0035078 (renal failure)
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The number of patients with significant chronic renal failure is expanding rapidly in the United States. All physicians and medical-care providers will have an increasingly important role in the detection and management of renal failure in patients who are not undergoing dialysis. Patients with diabetes or hypertension should be carefully monitored for the development of renal insufficiency by using screening tools such as blood pressure measurement, determination of serum creatinine, urinalysis, and determination of 24-hour urinary microalbuminuria. In order to slow the progression of renal disease, attenuate uremic complications, and prepare patients with renal failure for renal replacement therapy, all medical-care providers should "take care of the BEANS." Blood pressure should be maintained in a target range lower than 130/85 mm Hg, and in many patients, angiotensin-converting enzyme inhibitors may be beneficial. Erythropoietin should be used to maintain the hemoglobin level at 10 to 12 g/dL. Access for long-term dialysis should be created when the serum creatinine value increases above 4.0 mg/dL or the glomerular filtration rate declines below 20 mL/min. Nutritional status must be closely monitored in order to avoid protein malnutrition and to initiate dialysis before the patient's nutritional status has deteriorated. Nutritional care also involves correction of acidosis, prevention and treatment of hyperphosphatemia, and administration of vitamin supplements to provide folic acid. Specialty referral to nephrology should occur when the creatinine level increases above 3.0 mg/dL or when the involvement of a nephrologist would be beneficial for ongoing management of the patient.
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PMID:A practical approach to the management of patients with chronic renal failure. 1008 97

This article describes one hospital's system of providing epoetin therapy for patients with renal failure undergoing dialysis. Nurses complete a drug dosing worksheet which alerts pharmacists to the need for both epoetin and iron dextran doses. The patient's weight and hematocrit are included on the form as are initial dose calculations made by the nurse. Pharmacists use this information for patient monitoring and double checking dose calculations. Then individually packaged unit dose injectables are prepared by pharmacy for use by nurses. A drug use evaluation for epoetin assures that appropriate use criteria are fulfilled when epoetin is used.
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PMID:A system for monitoring and dispensing epoetin. 1010 8

The quality of life of patients with end-stage renal disease (ESRD) has become an area of intensive investigation because of the high costs of renal-replacement therapy (dialysis or renal transplantation) and the rising prevalence of renal failure. Studies comparing quality of life of patients using different forms of renal-replacement therapy are flawed by deficiencies in study design, such as lack of randomisation. Nevertheless, in both retrospective and prospective studies, transplantation has been shown to offer the highest levels of functional ability, employment and subjective quality of life. After case-mix adjustment, there is little difference between peritoneal dialysis and haemodialysis in terms of quality-of-life (QOL) outcomes. Vocational rehabilitation is an important aim of therapy; for patients below retirement age, pre-dialysis education and counselling are important in maintaining employment. The elderly comprise the fastest-growing group of dialysis recipients; multiple comorbidities add to functional impairment in these patients. Subjective quality of life remains surprisingly high in many elderly patients, despite poor objective quality of life. The quality of life of patients with diabetes mellitus and ESRD is lower than that of nondiabetic patients with ESRD. For selected patients with insulin-dependent diabetes mellitus, combined renal and pancreatic transplantation offers the advantage of freedom from insulin injections. Unfortunately, available evidence suggests only small improvements in quality of life with combined transplantation versus kidney-only transplantation, probably because many patients have developed multiple diabetic complications by the time of transplantation. Epoetin alfa (erythropoietin) has been shown to improve quality of life in a number of trials. The optimal target haematocrit is a subject of controversy, but on current evidence, a target of 34 to 37% is reasonable. The degree of improvement in quality of life must be balanced against the additional costs of achieving a higher haematocrit. Further study is necessary to clarify the optimal target haematocrit for epoetin alfa therapy, as well as the possible effects of nutritional support, growth hormone in paediatric patients, and combined renal and pancreatic transplantation in improving quality of life.
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PMID:A review of quality of life in chronic renal failure. 1016 67

Approximately 50% of cancer patients develop anemia. In the past, the only available treatment option for these patients was transfusion. Since the late 1980s, recombinant human erythropoietin (rHuEPO, epoetin alfa [Epogen, Procrit]) has provided a treatment alternative. Controlled clinical trials have shown that rHuEPO increases hemoglobin and hematocrit levels and reduces the need for transfusions in patients with cancer-related anemia. These controlled trials have suggested (as larger, uncontrolled studies) that the improvements in hemoglobin are associated with increases in energy level, functional status, and overall quality of life. However, only about 50% of patients respond adequately to usual doses of rHuEPO. In the chronic renal failure population, functional iron deficiency is the most common cause of inadequate response to rHuEPO. It has been hypothesized that functional iron deficiency may also occur in cancer patients receiving rHuEPO and may account for the lack of response in up to half of those patients. Studies in renal failure patients have shown that administration of intravenous iron can correct functional iron deficiency more effectively than oral iron and may improve response to rHuEPO. Intravenous iron also reduces the total amount of rHuEPO needed to normalize hematocrit and hemoglobin levels, thereby reducing treatment costs. Ongoing clinical trials are evaluating whether IV iron can also improve rHuEPO responsiveness in patients with cancer-related anemia.
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PMID:Role of iron in optimizing responses of anemic cancer patients to erythropoietin. 1023

Erythropoietin (Epo) controls the proliferation, differentiation and survival of the erythroid progenitors. Epo exerts its effects by binding to a cell surface receptor. The Epo receptor includes a p66 chain, which is dimerized upon Epo activation, and two accessory proteins, which have been defined by cross-linking. Epo binding induces stimulation of the Jak2 tyrosine kinase. Jak2 activation leads to the tyrosine phosphorylation of several proteins, including the Epo receptor itself. Different intracellular pathways are activated: Ras/MAP kinase, phosphatidylinositol 3-kinase and STAT transcription factors. However, the exact mechanisms by which the proliferation and/or differentiation of erythroid cells are regulated after Epo stimulation are not known. Target disruption of both Epo and Epo receptors showed that Epo is not involved in the commitment of the erythroid lineage; it seems to act mainly as a survival factor. Epo is synthesized largely by the kidney and the liver, and sequences required for tissue-specific expression have been localized in the Epo gene. A 3' enhancer is responsible for hypoxia-inducible Epo gene expression. Hypoxia-induced factor-1 (HIF-1) protein binds to this enhancer. In addition to anaemia of renal failure, the indication for treatment with epoetin has been extended to the anaemia of chronic diseases.
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PMID:The molecular biology of erythropoietin. 1033 64

Anaemia is a common problem in patients with renal failure, whether or not they are on dialysis. There is a continuum of declining renal function. In addition, the creatinine clearance at which dialysis is initiated varies widely between institutions and between studies. The term 'progressive renal insufficiency' is therefore preferable to 'pre-dialysis'. The adverse effects of renal anaemia on left ventricular mass become apparent early in the course of progressive renal insufficiency; 75% of patients starting dialysis already have left ventricular hypertrophy (LVH). Correction of anaemia in patients with progressive renal insufficiency has been shown to improve physical function and anaemia-related symptoms, but no controlled studies have yet been conducted to determine its effects on LVH. Although one animal study generated some concern that epoetin may exacerbate a decline in renal function, there is no evidence from human studies for any such effect. Treatment of anaemia with epoetin in anaemic patients with progressive renal insufficiency is therefore recommended, provided blood pressure is controlled. To date, however, there are insufficient data to determine whether normalization of haemoglobin is advisable in this patient group. Detection and correction of iron deficiency is important to achieve the full benefits of epoetin, though recommendations cannot yet be made regarding the optimum route and timing of iron supplementation in patients with progressive renal insufficiency. In these patients the role of other adjuvant therapies, such as L-carnitine, vitamin B6, vitamin B12 and folic acid, also requires further investigation.
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PMID:How should anaemia be managed in pre-dialysis patients? 1033 70

Cancer-related anaemia has a number of causes, not least the underlying malignancy itself which plays a role in suppressing erythropoiesis. Anaemia is often exacerbated by cancer treatments, in particular routinely used cytotoxic chemotherapy. Chronic anaemia of cancer is often characterized by inappropriately low levels of endogenous erythropoietin for the degree of anaemia, and manifests clinically with generalized hypoxia and resultant severe fatigue. Epoetin alfa is one recombinant form of erythropoietin, the primary human growth factor responsible for promoting proliferation and survival of erythroid progenitor cells. Epoetin alfa has been widely studied for the treatment of anaemia associated with renal failure and is now recognized as having significant potential in the management of cancer-related anaemia. Studies suggest that epoetin alfa is an effective treatment in a proportion of cancer patients with symptomatic anaemia. It also appears useful for the prevention of chemotherapy-induced anaemia. Studies in a number of different cancer settings have shown that epoetin alfa significantly increases haemoglobin and haematocrit, reduces transfusion requirements and improves quality of life for the patient.
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PMID:Epoetin in cancer-related anaemia. 1033 73

Recombinant epoetin therapy and correction of the chronic anemia of renal failure have greatly reduced the number of red cell transfusions and hence the propensity to iron overload. The majority of HD patients require intravenous iron therapy to achieve the hematocrit levels that correspond to improved outcome measures. Although the short-term benefits of intravenous iron have been clearly defined, the long-term risks of intravenous iron are less well-defined. Iron overload before the availability of epoetin constituted a serious problem; our review of the literature does not decisively conclude that these patients had more serious bacterial infections or increased mortality when compared with their non-iron overloaded counterparts, unless chronic transfusion-related hepatic disease was superimposed. Specifically, no data unequivocally confirm that iron overload from parenteral iron contributes to all-cause patient morbidity or mortality. Furthermore, therapy that maintains intravenous iron optimal iron stores and replaces iron losses associated with the dialytic procedure does not engender iron overload in the carefully monitored patient. Optimized anemia therapy in ESRD requires individualized and specific application of epoetin and iron for each patient, and significant cost savings can result from such a strategy. Prospective studies are clearly necessary to define those parameters that reflect adequacy of iron storage in renal failure patients. We should develop alternative means of iron delivery and develop monitors that accurately discriminate between patients who will respond to additional iron therapy and those who will not. Whether ferritin should be supplanted by another parameter and whether iron itself poses an increased risk to those patients it has so beneficially served are issues that must be resolved. Until these answers are known, the importance of carefully crafted iron therapy cannot be overstated.
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PMID:An indistinct balance: the safety and efficacy of parenteral iron therapy. 1047 57

Erythropoietin (EPO) has revolutionized the treatment of anemia in renal failure patients, both in the pre- and postdialysis phase. Not only does the treatment improve well being, but also it positively influences cardiac function and permits cardiac hypertrophy to regress. EPO can lead to an increase in blood pressure; the mechanisms of this effect are not entirely clear. By optimizing dialysis treatment, paying close attention to volume regulation, giving EPO subcutaneously and in a fashion to increase hematocrit gradually, the occurrence of blood pressure increases can be minimized. Hypertension has not proved to be a serious general problem in the EPO treated patient.
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PMID:Erythropoietin and arterial hypertension. 1074 8

In evaluating outcomes in end-stage renal disease (ESRD), quality of life has become as important as morbidity and mortality. Various instruments are available to analyse patients' perceptions of the physical, psychological and social domains of health. Non-specific instruments, such as the Sickness Impact Profile, the Karnofsky Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), have been widely used in evaluating quality of life in various chronic diseases including ESRD. The Kidney Disease Quality of Life (KDQOL) questionnaire and other scales have also have been developed specifically for ESRD patients. Several studies have demonstrated a significant improvement in quality of life after initiation of epoetin treatment in both dialysis patients and those with early renal failure. Quality-of-life scores show a strong positive correlation with haemoglobin concentration. Other factors associated with better quality of life are higher socio-economic level and level of education. However, older age, comorbidity, diabetes, female sex, and unemployment have a negative influence on quality of life. In patients not yet on dialysis, quality of life deteriorates as the glomerular filtration rate decreases. The later the patient is referred to a nephrologist, the worse the quality of life. Recent studies show that quality of life is a prognostic factor for survival. Early and effective treatment of anaemia in ESRD patients is essential in maintaining quality of life both before and after initiation of dialysis.
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PMID:Quality of life benefits of early anaemia treatment. 1103 54


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