Trends in clinical indicators of care for adult peritoneal dialysis patients in the United States from 1995 to 1997. ESRD Core Indicators Workgroup.
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BACKGROUND: This article describes the changes in four core indicator variables: dialysis adequacy, hematocrit, serum albumin, and blood pressure in peritoneal dialysis CAPD and cycler patients over a three-year period. METHODS: A national random sample of adult peritoneal dialysis patients in the United States was drawn each study period. Clinical data abstraction forms were completed by facility staff for patients selected for the sample, returned to the respective network, then forwarded to the Health Care Financing Administration for analysis. RESULTS: The mean weekly Kt/V urea for CAPD patients increased from 1.91 in 1995 to 2.12 in 1997 (P < 0.001) and for cycler patients, from 2.12 in 1996 to 2.24 in 1997 (P < 0.05). The mean weekly creatinine clearance for CAPD patients increased from 61.48 liter/week/1.73 m2 in 1995 to 65.84 liter/week/1.73 m2 in 1997 (P < 0.05). For cycler patients, it increased from 63.37 liter/week/1.73 m2 in 1996 to 67.45 liter/week/1.73 m2 in 1997 (P < 0.05). Despite this increase in adequacy values, less than 40% of peritoneal dialysis patients in 1997 had weekly Kt/V urea or creatinine clearance values that met subsequently published National Kidney Foundation's Dialysis Outcomes Quality Initiative (DOQI) guidelines. These data suggest that the dialysis prescription may not be adequately modified to compensate for increased body weight and for decreased residual renal function as years on dialysis increase. The average hematocrit value increased modestly in both CAPD and cycler patients from 1995 to 1997, and the number of patients with a hematocrit of less than 25% decreased from 6% in 1995 to 1.4% in 1997 (P < 0.001). Both serum albumin values and systolic and diastolic blood pressure values were essentially unchanged during the three-year period of observation. CONCLUSIONS: Despite improvements in dialysis adequacy and hematocrit values, there remains much room for improvement in these core indicator values. (+info)
Continuous delivery of human and mouse erythropoietin in mice by genetically engineered polymer encapsulated myoblasts.
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The transplantation of polymer encapsulated myoblasts genetically engineered to secrete erythropoietin (Epo) may obviate the need for repeated parenteral administration of recombinant Epo as a treatment for chronic renal failure, cancer or AIDS-associated anemia. To explore this possibility, the human and mouse Epo cDNAs under the control of the housekeeping mouse PGK-1 promoter were transfected into mouse C2C12 myoblasts, which can be terminally differentiated upon exposure to low serum-containing media. Pools releasing 150 IU human Epo per 10(6) cells per day and 390 IU mouse Epo per 10(6) cells per day were selected. Polyether-sulfone (PES) capsules loaded with approximately 200,000 transfected myoblasts from these pools were implanted on the dorsal flank of DBA/2J, C3H and C57BL/6 mice. With human Epo secreting capsules, only a transient increase in the hematocrit occurred in DBA/2J mice, whereas no significant response was detected in C3H or C57BL/6 mice. On the contrary, all mice implanted with capsules releasing mouse Epo increased their hematocrit over 85% as early as 7 days after implantation and sustained these levels for at least 80 days. All retrieved implants released Epo and contained well preserved myoblasts. Moreover most capsules were surrounded by a neovascularization. Mice transplanted with nonencapsulated C2C12 cells releasing mouse Epo showed only a transitory elevation of their hematocrit reflecting the poor engraftment of injected myoblasts. These results indicate that polymer encapsulation of genetically engineered myoblasts is a promising approach for the long-term delivery of bioactive molecules, allowing the resolution of the shortcomings of free myoblast transfer. (+info)
The molecular biology of erythropoietin.
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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. (+info)
What are the short-term and long-term consequences of anaemia in CRF patients?
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There is a clear relationship between anaemia and cardiovascular risk in chronic renal failure (CRF) patients. Left ventricular hypertrophy (LVH) is present in about three-quarters of patients starting dialysis, and is a strong predictor of mortality. Anaemia contributes to the development of LVH, mainly via increased cardiac output. In some patients, anaemia results in an increase in LV mass, while in others it also results in LV end-diastolic volume dilatation. These changes increase the risk of arrhythmias, myocardial infarction and myocardial fibrosis. The lower the haemoglobin, the more likely it is that LVH and heart failure will develop. Furthermore, a haemoglobin of < 11 g/dl is associated with increased morbidity and mortality. Partial correction of anaemia with epoetin leads to a partial, but not complete, reversal of LVH. One large prospective study (Lombardy Registry) found that epoetin treatment was accompanied by a 30% reduction in crude relative risk of mortality. A progressive reduction in the relative risk of general and cardiovascular mortality was found with increasing haematocrit, with and without adjustment for co-morbid conditions. Mean hospitalizations also decreased with increasing haematocrit. The long-term effects of normalized haematocrit/haemoglobin values in uraemic patients have not yet been evaluated exhaustively in prospective, randomized, multicentre studies. Epoetin treatment has been shown to induce lasting improvements in patients' sense of well-being, reduce fatigue, increase appetite and work capacity, and improve exercise tolerance, libido and work performance. Further studies are needed to demonstrate whether greater haemoglobin concentrations are associated with greater improvements in quality of life during epoetin treatment. (+info)
Is there a role for adjuvant therapy in patients being treated with epoetin?
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Adjuvant therapy may allow patients being treated with epoetin to derive greater clinical benefits. Iron supplementation is currently the most widely used form of adjuvant therapy; intravenous (i.v.) iron is required by the majority of haemodialysis patients receiving epoetin. Measurement of hypochromic red blood cells is the most direct way of assessing iron supply to the bone marrow. During the correction phase, a dose of i.v. iron equivalent to 50 mg/day is recommended, with the total dose not exceeding 3 g. When subclinical vitamin C deficiency is suspected, ascorbic acid may be given orally (1-1.5 g/week) or i.v. (300 mg three times weekly at the end of dialysis). The active vitamin D metabolites alfacalcidol and calcitriol may, under some circumstances, improve anaemia and reduce epoetin dosage requirements. Vitamin B6 requirements are increased during epoetin therapy, and supplementation at a dose of 100-150 mg/week is recommended. Supplementation of vitamin B12 is optional. Folic acid is supplemented routinely in haemodialysis patients, though evidence that it increases the efficacy of epoetin is limited. Low doses (2-3 mg/week) should normally be sufficient to maintain optimal folic acid stores in epoetin-treated patients, although higher doses are necessary for patients with hyperhomocysteinaemia. L-Carnitine supplementation may be appropriate in some patients with anaemia of chronic renal failure (CRF) unresponsive to, or requiring large doses of, epoetin. Androgens potentially could reduce epoetin costs in countries with limited resources, but should only be used in men older than 50 years with a remnant kidney. Recent animal studies indicate that the combination of epoetin and insulin-like growth factor 1 might be beneficial in CRF patients. High doses of angiotensin-converting enzyme (ACE) inhibitors should be reserved for dialysis patients who have hypertension that cannot be controlled by other agents, or who require an ACE inhibitor for treatment of heart failure. (+info)
European best practice guidelines for the management of anaemia in patients with chronic renal failure.
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Best practice guidelines recommend management strategies and attempt to set standards for optimal patient care. The momentum towards formulating guidelines comes not only from health care professionals, but also from health care management organizations, who need some way of measuring the quality of the services they purchase. The European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure have been drawn up by a Working Party including representatives of the European Renal Association/European Dialysis and Transplantation Association (ERA-EDTA) and the national nephrology societies of a cross-section of European countries. The guidelines draw on the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Best Practice Guidelines for the Treatment of Anemia in Chronic Renal Failure, but reflect European clinical practice and experience. They include additional publications, and new analysis and interpretation of the evidence base. Topics covered in the European guidelines include diagnosis of the anaemia of chronic renal failure, indications for starting treatment with epoetin, recommended minimum target haemoglobin concentrations, epoetin dosage and route of administration, assessing and optimizing iron stores, causes and management of epoetin resistance, and possible adverse effects of epoetin treatment. The guidelines are not intended to be prescriptive but rather to provide clinical guidance based on the best available evidence. The evidence supporting each guideline is graded, so that physicians may judge its reliability. (+info)
How should anaemia be managed in pre-dialysis patients?
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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. (+info)
Epoetin in cancer-related anaemia.
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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. (+info)