Masters of Nursing Project


 


AN AUDIT OF ACHIEVED TARGET HEMOGLOBIN LEVELS AS PER CARI GUIDELINES IN STABLE HEMODIALYSIS PATIENTS OF ALICE SPRINGS


 


 


Research plan


Research question/goals of the project


 


Research question


Research question plays a role in understanding the research focus investigated and integrates a causal relationship to the organization of the research literature review which serves for a critical assessment regarding to the audit of target hemoglobin levels into CARI guidelines pointing towards stable hemodialysis patients with focus group of Alice Springs, in Australia. The core research question for this research study is to recognize what is the comparison between epoetin and darbepoetin in the treatment of anemia of renal failure in stable dialysis patients of Alice Springs? Aside, initial research questions are needed in order to understand more of the pressing situation and be able to determine good resources and knowledge about the research being ideally manifested and explained in the literature review context and formation.


 


  • What does CARI guidelines mean? How the guidelines functions into target hemoglobin levels? Determine usage among hemodialysis patients in Alice Springs

  • What is the definition of anemia of chronic renal failure? And, how the situation affects renal patients?

  • How important is epoetin and darbepoetin in treating anemia in patients with chronic renal failure? And why anemia treatment is important? Discuss.

  • What is known and unknown, as it can be on animals or other areas like in the field of oncology and or renal disease?

  •  


    Research Goals


     


    The following points are the specific goals to be achieved in this research organization wherein there is the need to:


     


  • Find out the difference in the effectiveness of epoetin versus darbepoetin in treatment of anemia in dialysis patients

  • Find out if Alice Springs dialysis patients on epoetin and darbepoetin achieved targeted hemoglobin levels compared to CARI guidelines.

  •  


    Research Background


     


    Research is an essential factor for any success of nursing project and it serves as first hand and direct means of bringing in concepts and theories together in one paper, the methods and analysis plays a crucial supporting part to the organization of the literature review for the research focus, the need to have rigorous research planning and spontaneous gathering and collating of thoughts forming in primary and secondary research domains. Indeed, the identification of such audit is deemed upon achieving target hemoglobin levels from within CARI guidelines, study on hemodialysis patients in Alice Springs to be specific. There needs to realize at the same time adopt such inclusion of modes for treating anemia of renal failure, linking towards epoetin and darbepoetin assimilation and detection.


     


     


     


     


     


    Ideally, in Australia, there strikes differences in geographic sense of the situation as people living in the remote places does have high hospitalization rates as being attributed to difference in socioeconomic status and the access to health services, as Alice Springs posing in indigenous Australians does constitute number of patients commencing anemia into renal disease treatment. Even though epidemics of renal disease among Australians are duly documented, there can be no presence of research and reports dealing to CARI utilization of hemodialysis patients in Alice Springs. Anemia assumes complication of chronic kidney disease that is seen in more than eighty percent of patients with impaired renal function (Melnikova, 2006). Moreover, during the year 1990, epoetin was licensed in the United States and Europe for the treatment of anemia associated with chronic renal failure, the patients on dialysis is an example group, as epoetin is highly effective at stimulating erythropoiesis and produces a consistent increase in hemoglobin levels. The patient’s capacity for physical and cognitive function is increased and physiological function is improved. The ideal efficiency of epoetin may be primarily limited by the need for its frequent administration of recovery process. Furthermore, Darbepoetin which is a second-generation erythropoiesis-stimulating agent contains 2 amino acid substitutions, which provide the protein with greater metabolic stability in vivo and increase the elimination half-life when compared with intravenous epoetin. Thus, Darbepoetin can be administered once weekly or once every other week for example there has been a randomized research being conducted in approximately five hundred hemodialysis patients demonstrated that once-weekly darbepoetin was as effective in maintaining hemoglobin levels as epoetin dosed 3 times weekly for the treatment of anemia. Aside, there indicated that the hemoglobin level for these subjects was maintained within -1.0 to +1.5 g/dL of their baseline hemoglobin and between 9.0 and 13.0 g/dL over 28 weeks as noted by the American Society of Nephrology Annual Meeting in the year 2006 (Macdougall, 2006; Rao and Pereira, 2006), the hemoglobin variability are not influenced by the type of erythropoietic agent used for the treatment of anemia. Initially, patients with stable hemoglobin were being extended to constant injections of darbepoetin with appropriate dosage adjustment of the patient, as the proportion of patients who were being treated are doubled within the dose of darbepoetin as compared to the other. However, despite successes of epoetin and darbepoetin, anemia management linking to renal failure is poised for clinical advancement since, there can be some innovative anemia therapies are in diverse stage of development (Nissenson, Krishnan, Liu et al, 2006; Simon, McLean, Halloran, et al, 2006). Thus, the need to review and compare data concerning the activityof epoetin versus darbepoetin, when administered topatients with renal failure upon experiencing treatment of anemia, from several journals and articles in academic reviewed reality.The integration of significant knowledge are to be extracted from published article and journal reports as well as comprehensive studies of patients undergoing hemodialysis due to renal failure as developed treatment to anemia as being treated withepoetin alfa or darbepoetin alfa.Synthesis can assume that epoetin alfa and darbepoetin alfa are similaragents with identical indications for treatment of anemia in hemodialysis patients of Alice Springs in Australia as the two agents can significantly improve hemoglobin levels, reducetransfusion requirements as well as improve life among patients.


     


    Research Significance


    The research significance of this research focus is to be able to provide good research material and knowledge acquisition for the readers of this research, to be aware of the presence of anemia in patients with renal failure and is undergoing hemodialysis. To allow researchers and medical authorities/team in Australia to have a quick assumption and direct idea of hemoglobin levels as being properly indicated into the CARI guidelines, to bring in awareness that the situation is not easy to handle and resolve therewith, providing patients at Alice Springs options for treating anemia of such renal failure centering on hemodialysis patients thus, giving them ideas and knowledge content of certain epoetin and darbepoetin for anemia treatment as well as knowing the underlying value and importance is a must in this research.


     


    Literature Review


    The literature review study have demonstrated that, the unit dosing of darbepoetin alfa in stable dialysis patients can effectively and safely maintain haemoglobin concentrations within the recommended target range after switching from alfa or beta to darbepoetin alfa at reduced dose frequency. Mean haemoglobin concentrations were maintained above 11 gudl throughout the evaluation period, regardless of route, and frequency of administration. It is of note that darbepoetin alfa administration resulted in a higher increase in haemoglobin concentration compared with darbepoetin alfa. Following administration, there was an increase in haemoglobin of 0.6 gudl relative to baseline, associated with a decrease of weekly.


     


     


     


    There can be no change in haemoglobin concentration, or in darbepoetin alfa dose was observed from baseline to the evaluation


    period. Moreover, regardless of Hb category at baseline following administration there was an increase in Hb concentration that was


    associated with a decrease in weekly dose requirements. The observation that and darbepoetin alfa dose requirements were not different at evaluation. Randomized cross-over study by Kaufman


    et al. confirmed a number of previous reports and demonstrated that dose requirements for the situation when administration is approximately one-third higher than for dose requirements in order to


    maintain a similar haemoglobin concentration. The implication with


    darbepoetin alfa are of practical clinical significance, and could lead to changes in the management of renal anaemia. It has been common practice in Europe to administer the process route to hemodialysis patients such as for economic reasons, as there is a demonstrated


    dose-sparing effect. Using darbepoetin alfa by route in hemodialysis patients may provide improved outcomes, that this can be achieved within recommendations of the CARI guidelines deemed for the target haemoglobin concentrations in the treatment of renal anaemia.


     


     


     Furthermore, the ability to dose patients less frequently with darbepoetin alfa may have economic implications for healthcare providers, especially in relation to reduced nursing time, and not withstanding the improved convenience for the Alice Springs patients and there anticipates that further research study will address the issues of the topic in focus.


     


    Alice Springs Renal Care Area


    The majority of patients are Aboriginal, have relocated from remote areas of Central Australia to access treatment in Alice Springs. The facility caters for patients with different dependency levels and acuity, therefore no dialysis treatment is ever the same. Prescriptions and care are individualized to patient needs. The service supports haemodialysis care and offers related education. Specialist nursing staff are employed across the areas and have access and anaemia coordinator. Alice Springs Hospital, Flynn Drive unit incorporates a 2-station dialysis area, there enable access to dialysis for all acutely ill in-patients. Staff from the satellite site coordinates inpatient dialysis within the hospital.


     


    The research study needs to be observational, retrospective review of the hospital wide use of darbepoetin and epoetin such as for hospital admission purpose. There implies that epoetin alfa is the genetically engineered form of endogenous erythropoietin that has become the standard of care for erythropoietic support in renal anemia and cancer anemia. Replacement therapy with epoetin has been shown to increase RBC mass, to decrease the need for blood transfusions, and to reduce the symptoms of anemia. Aside, there is also implications towards darbepoetin alfa for the treatment of anemia associated  kidney disease as darbepoetin is a modified version of epoetin that has a significantly longer serum half-life, decreased clearance of darbepoetin allows this drug to be administered less frequently than epoetin. Currently, it is recommended that darbepoetin be given once every one to two weeks, whereas epoetin is given two or three times per week, For example, there can be patient requiring erythropoietic support may need to visit clinic two or three times per week to obtain an injection of epoetin. With darbepoetin, the decreased number of injections may translate into fewer clinic visits. The use of epoetin and darbepoetin results from the initiation or continuation of clinical treatment that is appropriate for monitoring in the outpatient setting. Labeled indications for epoetin consist mostly of chronic diseases treated on an outpatient basis, and clinical practice supports that role. Meanwhile, there can be findings that darbepoetin and epoetin to be equally safe and effective and to be interchangeable at specified dosages.


     


    About CARI Guidelines


    In Australia, national guidelines for treating patients with chronic kidney disease, the Caring for Australasians with Renal Impairment (CARI) guidelines are published and disseminated to nephrologists in March 2000, with details and updates on the CARI website at, <www.cari.org.au>. The guidelines do provide nephrologists, renal nurses and other health care providers with an evidence base for patient management and improving outcomes. The focus of one of the CARI guideline is anaemia, a common complication of chronic kidney disease. Management of iron levels in patients with chronic kidney disease involves both excluding iron deficiency in uraemic–anemic patients, and providing adequate iron stores to allow patients to efficiently maintain target hemoglobin concentrations, especially with the concomitant use of supplementary erythropoietin proteins. Failure to achieve adequate iron stores and availability is the major cause of epoetin resistance, which may result in increased costs to correct the anaemia. In observational studies of haemodialysis patients, it has been shown that the relative risk of death and hospitalization increases significantly with hemoglobin levels below the target. In an effort to understand the impact of guidelines, our study was designed to evaluate the outcomes of a standard implementation strategy of the


    CARI guidelines using an example, anemia management of dialysis patients in Australia. In assessing the strategy, the need to identify barriers to guideline implementation from the process of care approach, with a view to developing strategies to increase uptake of evidence into practice and that lessons learned from this process can be applied into clinical environments. Moe research into the needs of hemodialysis patients is required to determine their particular requirements and the applicability of the CARI guideline to Alice Spring patients. There is a growing body of research on how evidence is taken up into clinical practice. The most common strategies in use are, continuing medical education and passive dissemination of guidelines have consistently been shown to have very little impact on practice patterns or improving patient outcomes. The successful implementation of guidelines, it is necessary to devise a strategy or plan for the project. Research into effective methods for implementing clinical practice guidelines lags behind the research methods involved in producing guidelines. There highlights the possible barriers to implementing the CARI guideline for iron. To truly gain an understanding of which guideline implementation methods are most successful, controlled-intervention observational studies and completion of the quality cycle, with critical review of the achievement of targets, should be undertaken in renal medicine. Passive dissemination of the CARI guideline raised awareness of guideline, but improving iron management and patient outcomes will take commitment to change within the renal care team, an agreed iron protocol with a decision support aid, a working process for iron management, and skills improvement for renal nursing staff. Factors affecting iron management and barriers to change are numerous. For successful guideline implementation, a strategy to overcome these barriers in individual units should be planned and executed. Successful implementation of the guidelines is not achieved by forcing physicians to obey “rules”, but rather by creating an environment in which they are given the skills, knowledge, attitudes and support systems to help them provide their patients with the best possible care, based on the best possible evidence. Henceforth, it can be reasonably assumed that clinicians should have a high degree of confidence in the recommendations and a low threshold for implementation. Because the guidelines are generally considered by expert panels that assess the same evidence, there is a consistency of recommendations for the management of anemia across national and Alice Spring guidelines to a degree that is not observed in areas where there is less evidence


     


    Define anemia of chronic renal failure. How it affects renal patients?


    The anemia of renal failure is usually characterized by normochromic and normocytic blood cells. There is usually hypoplasia of the erythroid precursors in the bone marrow with little or no interference with normal leukopoiesis as well as mega karyocytopoiesis. On blood smears one may find typical, although not exclusive, spiculed and deformed red cells with any chronic anemia, compensatory mechanisms come into play in order to maintain acceptable levels of tissue oxygenation, and they consist mainly of increased levels allowing cases of lowered peripheral and vascular resistance (Simon, McLean, Halloran, S et al., 2006; Rastogi and Nissenson, 2006). The most convincing demonstration that specific toxins were the responsible for the shortened red cell survival was obtained with the introduction of dialysis. Dialysis improved, to a limited extent, the anemia in chronic renal failure patients although some of the research finding could not be ascribed to prolong the Hb level survival as there conforms to better utilization of iron and blood count production as seemed to be determinant for the treatment. The hemodialysis patients may show a diminishing anemia prevention requirement after initiation of hemodialysis approach. Besides, hemodialysis patients in Alice Springs can worsen the anemia due to the procedure associated blood losses and mild effect on oxygen transporting function, be associated with chronic dialysis leading to a sequestration of erythrocytes and further destruction of circulating red cells. The mainstay of the treatment of anemic patients is the use of epoietin and that response to treatment is impressive and the need for transfusion is importantly decreased. Upon initiation of therapy a target blood levels should be completely evaluated (Simon, McLean, Halloran, S et al., 2006; Rastogi and Nissenson, 2006). Thus, the start of the anemia treatment should be gradual to avoid excessively rapid increases in the red cell mass with its hyperviscosity consequences and weekly dose for hemodialysis patients can be an adequate therapeutic regimen. Furthermore, the anemia of chronic disease is immune driven as such the cytokines and cells of the reticuloendothelial system induce changes in iron homeostasis, the proliferation of erythroid progenitor cells, the production of erythropoietin and human life span of red cells, all of which contribute to the pathogenesis of anemia as erythropoiesis can be affected by disease underlying anemia of chronic renal disease through possible severe infection. Indeed, anemia with chronic kidney disease shares characteristics of anemia of chronic disease, although the decrease in the production of erythropoietin, mediated by renal insufficiency and the anti proliferate effects of accumulating uremia toxins, contribute importantly (Cass, Cunningham, Snelling, et al., 2003; Curtis, Ravani, Malberti, et al., 2005). In addition, the patients with anemia from within renal disease, chronic immune activation can arise from contact activation of immune cells by dialysis membranes, from frequent episodes of infection, or from both factors, and such Alice Spring patients can be present along with changes in the homeostasis of body iron that is typical of anemia of chronic disease.


    How anemia of chronic renal failure affects renal patients?


    In a person with normal renal function, the finding of anemia on routine blood analysis would prompt a work-up to determine the ultimate cause. In chronic renal failure, anemia is almost always present, and can be a result of any of the mechanisms listed above. However, the ideal anemia of chronic renal dearth (Simon, McLean, Halloran, S et al., 2006; Rastogi and Nissenson, 2006) is an outcome of decreased production of red blood cells by the kidney organ. The defect in red blood cell production is largely explained by the inability of the failing kidneys to secrete the hormone erythropoietin as the hormone is a necessary stimulus for normal Hb level to produce red blood cells. In addition, anemia Hb factors associated with renal failure, including the accumulation of some toxins does play vital role in depressing bone marrow function. Excess stores of aluminum may accumulate in the bone marrow of long term dialysis patients and can contribute to anemia as well. Aside, blood 1oss and red blood cell destruction also frequently contribute to the anemia in patients with renal failure. Platelets, which are small constituents of blood which aid in blood clotting, do not work normally in uremia. The defective blood clotting seen in uremia makes bleeding more common. Normally, red blood cells survive for about few months before being destroyed (Simon, McLean, Halloran, S et al., 2006; Rastogi and Nissenson, 2006). The hemodialysis patient survival can be reduced even with the prevalence of the chronic renal failure, probably because of chemical effects of anemia and decreased flexibility of the hemoglobin cell domains, hemodialysis can be mild and that patients having a stable condition are easily compensating the increasing target of the Hb cell production.


    What is the role of hemodialysis in the anemia of chronic renal failure?


    The effectiveness of dialysis in reversing any complication of uremia depends on the nature of that complication. Those disturbances which are due to accumulation of a uremic toxin may be reversible if that toxin is dialyzable and if the removal rate by dialysis outstrips its generation rate. Some improvement in red blood production is seen with initiation of dialysis, probably by decreasing the toxic effect of uremia on the marrow. Thus, the process of hemodialysis does not replace the hormone producing functions of the kidney and therefore does not by itself correct the main cause of anemia, namely deficient production of erythropoietin. Also, the presence of a simple dialysis approach does correct the bleeding tendency seen in uremia, but not to normal. Hemolysis may occur for patients in Alice Springs if, there are problems with the dialysate. Thus, several folate as well as water soluble vitamin necessary for normal Hb level production can be dialyzable and helps the patients of renal care. Generally, dialysis patients are given oral supplementation with folic acid in case their normal diet does not supply them with sufficient folate to keep up with its loss through dialysis (Mendelssohn, 2005; National Public Health Partnership, 2001; Roderick, Jones, Drey et al., 2002). The treatment of the anemia of chronic renal failure has changed dramatically in recent years. Until recently, the principal treatments were transfusion of red blood cells and administration of the hormone testosterone. Although transfusions will rapidly correct a low blood count, repeated transfusions are associated with some problems, including iron overload, the development of certain antibodies and the possibility of viral infections. Thus, the use of erythropoietin is constrained by the extremely high cost of the hormone as well as CARI policies of health care service as well as Medicare benefits (Roderick, Jones, Drey et al., 2002).


    Importance of epoetin and darbepoetin and why treatment is important?


    In most cases, epoetin alfa and darbepoetin alfa, which mimic the actions of erythropoietin, are currently being used to correct anemia and have been shown to reduce the need for transfusions. There reported that no clinically significant differences in the effectiveness of epoetin and darbepoetin for managing anemia in patients who are undergoing such treatment. There sought to determine whether darbepoetin, there can be a longer acting drug that requires fewer injections than epoetin, differed from epoetin in its ability to achieve key treatment goals. Both drugs reduce the need for transfusion, but the report found no clinically significant difference between the two agents for the anemia treatment upon improving hemoglobin concentration and in reducing transfusion (Bradbury, Fissell, Albert et al., 2007; Locatelli, Pisoni, Combe et al., 2004; Regidor, Kopple, Lovesdy et al., 2006). Several data were insufficient to answer the research questions regarding the utilization of the agents, such as recognizing appropriate target hemoglobin level, patient characteristics for predicting responses to anemia treatment, when treatment should be initiated or discontinued, optimum dose approach and duration of treatment. Thus, research gaps are to be identified, as some studies does not provide complete reporting on certain events, as epoetin and darbepoetin are given as a series of injections and can reduce the need for red blood cell transfusions and increase hemoglobin levels. However, these drugs also have risks, including the risk of serious or life-threatening blood clots


    Several initial literature findings regarding epoetin and darbepoetin are as follows: (Regidor, Kopple, Lovesdy et al., 2006)


  • Both were equally effective in increasing hemoglobin concentration.

  • No statistic significant difference was found in reducing the need for transfusion. About twenty five to thirty percent of the patients treated with epoetin or darbepoetin underwent transfusion as compared with forty percent of untreated patients.

  • No statistic difference was found in the rates of thromboembolic event as approximately seven percent of patients treated with either one of the treatment event, compared with four percent of untreated patients.

  • The quality of life measures tended to favor treatment with either drug, but individual trial results were variable and no clear method for interpreting changes in anemia-specific quality-of-life measures.

  •  


    True that, the epoietin replacing proteins have improved patient outcomes and quality of life and that, current recent research has resulted in the develop­ment of a long-acting erythropoietin, darbepoetin, which is more convenient for administration by physicians and patients. Furthermore, darbepoetin has been proven to be effective in maintaining hemoglobin levels in chronic kidney disease patients within a monthly dosing schedule of the substance, the need for some therapeutic interchange program to convert therapy for all inpatients under­going dialysis from erythropoietin alfa to darbepoetin alfa for treatment of chronic kidney disease-related anemia has been implemented, the need to establish the efficacy and safety of the darbepoetin conversion of stable hemodialysis patients from the current short-acting alfa or beta to the long-acting darbe­poetin with an aim to check the appropriateness of the current ratio of conversion of the short acting to the long acting erythropoietin. The examining of data from Alice Springs, Australia with regards to the use of the two agents from within hemodialysis patients in Australia in such particular period from adhering to cross-sectional survey methodology from wherein there allows recognizing of hemoglobin concentration into hemodialysis patients. Although, the cross-sectional study cannot directly address issues of anemia of renal failure, there appears that such agents effectiveness have dissimilar  relationships with hemoglobin levels from within CARI and the measurement of hemodialysis utility as compared to limited research paradigm.


     


    Control of Hemoglobin


     


    From the research assimilation, the ability to maintain patients within target hemoglobin ranges is of increasing interest due to concerns over possible negative impact of high hemoglobin levels and the well documented negative effects of low hemoglobin levels. There can be studies of extended dosing regimens with darbepoetin alfa in chronic kidney disease patients on hemodialysis have shown maintenance of hemoglobin within target range in high proportion of Alice Springs patients, proportions of patients on dialysis also maintained hemoglobin within the target range while receiving darbepoetin alfa at extended dosing intervals, in a study by Mann et al., 85 percent of the patients treated with darbepoetin have maintained Hb


    in the target range from a similar proportions being observed in literature studies. In a study by Carrera et al., there asserted that, 105 hemodialysis patients stable on darbepoetin alfa QW have switched to darbepoetin alfaQ2W. The dose was titrated to maintain patient hemoglobin levels between 11 and 13 g/dL. Also, in a research study by Rutkowski et al, haemodialysis patients stable on BIW and or TIW epoetin, were switched to i.v. darbepoetin alfa administered QW for 24 weeks. The dose of darbepoetin alfa was adjusted to maintain patient Hb in the range 11–13 g/dL.


     


    Functions and Data based on CARI guidelines


     


    From within the CARI guidelines, the achieved target of hemoglobin levels is needed for stable patients in Alice Springs from controlling of anemia and poses initial treatment to the disease from within chronic renal failure prevalence. The sample from Flynne drive within the baseline domain, the assumed mean of the hemoglobin level can be ideal at 11.6 to 0.6 g/dl, as the hemodialysis centered patients at Alice Springs in Australia does acquire good percentage ratio of dosage of the epoetin agent and from where the example percentage can run to  48 percent up to 67 percent of the research assimilation of the study. Accordingly, there found initial difference in achieved hemoglobin


    level of the hemodialysis patients as the CARI guidelines does follow treatment protocol as well as management of anemia due to renal failure, and that there has been assumptions of  achieving in 1.9 g


    per deciliter in the current year and that, 1.7 g per deciliter in the succeeding years as well as approximately 1.5 g per deciliter from within the research sample in Australian context. Research information does imply details of weekly epoetin dose was 5000 IU among the hemodialysis patients that can be adopted at Alice Springs patients and that the two agents in treating anemia will stabilize the levels and concentrations of hemoglobin in the affected patients.


     


     


     


    Blood Pressure Control


    There is importance of attaining control of blood pressure in patients in order for the treatment to be an ideal one and with positive position as the normalization of the hemoglobin level serves as an important factor for keeping good track of the blood level in renal disease patients for Alice Springs, as not being associated with stable yet long term increase in the targeted hemoglobin monitoring and checking also of the blood pressure of patients in dialysis. The presuming baseline data can see systolic blood pressure which can be about 139 of 17 mm Hg as well as the diastolic blood pressure of possible 79 of 10 mm Hg into the research process and it can also be that the  systolic blood pressure will be 136 of 21 mm Hg and diastolic blood pressure which arise to 79 to 11 mm Hg. The value of the levels are significantly recognized for treating anemia of chronic renal failure. Despite higher rate of agent and or beta-blocker used for the patients as there can be no significant difference between hemodialysis patients from within numbers of Alice Spring patients comprising of 160 based from the research population, as there one ideal usage of the agent at the baseline data for achieved hemoglobin level. Another, study by Bradbury et al. (2007) and Regidor et al. (2006), had pointed that, several prescriptions for angiotensin II–receptor blockers, beta-blockers, and calcium-channel blockers increased by approximately 10 percent and prescriptions for alpha-blockers increased by approximately 15 percent with no significant differences between the hemodialysis patients into CARI integration at Alice Springs. Thus, the initiation of anemia treatment in dialysis patients targets a hemoglobin (Hb) level of 12 g/dl into 160 sample data in hospital records as little is known about how rapidly pts reach the target and how likely they are to exceed the target range. And that categorization of the Hb levels of <9, 9-<10, 10-<11, 11-<12, & 12 (Phrommintikul et al., 2007; Carrera and Macdougall, 2008) from the initiation based on the CARI guideline. Furthermore, research have asserted that, after a few months, approximately 90 percent of the patients have reached Hb >=11 g/dl respectively. The table and figures below shows the likelihood of reaching a Hb >12, >12.5 and >13 g/dl in the first weeks right after the first Hb >=11 g/dl. Indeed, roughly 85 percent  will exceed 12 g/dl, 70 percent have exceeded 12.5 g/dl, over half did exceed Hb level of 13 g/dl, regardless of Hb at initiation. Thus, hemodialysis patients who have lower Hb at initiation take longer upon taking the target hemoglobin levels, however once reaching the Hb target, the situation then are ideally equal to go past levels at around 12.5, and 13 g/dl.


     


     


     


     


    Correction of anemia appears to be highly associated with overshooting the target, which may reflect increased sensitivity of the patients to treatment. Exceeding the target may contribute to dosing changes and subsequent instability in patients’ Hb levels. Year


    Hb (g/dl)


    Cumulative probability of exceeding a


    Hb (g/dl) of 12, 12.5, and 13 within


    3 months after the first claim


    with Hb 11+; by initial Hb


     


     


    <9


    9-<10


    10-<11


    11-<12


    12+



    2002


    12+


    85.4


    84.8


    85.3


    83.2


    84.9


     



    12.5+


    71.0


    71.1


    70.8


    68.8


    67.7


     



    13+


    55.0


    55.0


    54.4


    51.6


    50.8


     



     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


     


    Aside, research study of the effect of hemoglobin level on patient outcomes suggest that a level below 11 g/dl is associated with poor outcomes. More recent literature research suggests that variability of Hb levels over time and cumulative time with Hb <11 g/dl (Mann, Kessler, Villa et al., 2007), for instance the showing of strong treatment association within poor CARI standards are to be avoided. One good point of research have assessed the effect of cumulative time with Hb <11 g/dl during a sixth month entry time on such reality of hospitalization and mortality of hemodialysis patients for Alice Springs in Australia. For one, there were incident renal affected patients being identified by target Hb levels during the current year. Literature shoes that, those who survived for at least nine months are being followed, from month 10, of hospitalizations and mortality at Alice Springs. Months 6 to 9 were used to characterize comorbidity from claims and to assess the patient-level number of months with Hb <11 g/dl. There are some patients being classified in such groups, those with Hb <11 g/dl for 0 or 1 month, and those with 2-5 months below 11 g/dl. A propensity model based on comorbidity predicted the probability of having greater than the mean time with Hb <11 g/dl. A proportional hazards model assessed the independent effect of time with Hb < 11 g/dl on time to first hospitalization and time to death. The mean number of months with Hb <11 g/dl were 36 percent of the patients had a cumulative number of months with Hb <11 g/dl greater than the mean factor, suggesting that the hemodialysis patients with Hb <11 g/dl for prolonged periods of time that have significantly greater risk of hospitalization and death that is regardless of stability status (Provenzano, Besarab, Macdougall et al., 2007; Burnier, Demay and Tanghe, 2007). Moreover, Yaqub (2001), indicated that, “hospitalization is common in renal disease patients on hemodialysis and the length of stay is than non dialysis patients. Indeed, the changes in hemodialysis patients’ level of anemia, occurring on or before hospitalization are described from a report that shows up target in hemoglobin from treatment organization of anemia”. The purpose of the retrospective analysis are to determine the distribution of Hgb changes in a large randomly selected sample of Alice Spring patients and to determine the length of time required to restore the Hgbs to control pressure levels. The hemodialysis patients based on CARI process does have at least one renal unit care stay of at most 20 days, with Hb values in the thirty days of the admission to the unit in the anemia treatment upon utilizing the agents. There can be assimilation that the mean hemoglobin levels were >11g/dL in 86 percent of the hemodialysis patients as monitored at Alice Springs, hemoglobin (g/dL), ng/mL and per treatment epoetin dose are shown below. The patients with higher serum ferritin levels required from the average situation, lower erythropoetin doses to maintain target hemoglobin levels >11g/dL as the levels may not be indicative of increased epoetin resistance from the population, as there contradict from the indication of epoetin resistance.


     


    Hemoglobin


    (g/dL)


    epoetin


    darbepoetin


    11.8


    9949


    420


    11.8


    8172


    1303


     


     


    Henceforth, the treating of anemia is being associated with chronic kidney disease may have several benefits including delayed progression of kidney disease. There evaluated the progression of kidney disease in anemic patients with chronic kidney disease receiving darbepoetin alfa. Hemodialysis patients are being treated into nurse directed anemia management clinic based on CARI protocol established with nephrologists. The sample patients (n=160) are being anemic (Hb ≤ 11 g/dL) at (Provenzano, Besarab, Macdougall et al., 2007; Burnier, Demay and Tanghe, 2007) enrollment and received darbepoetin alfa. Follow-up are between 3 and 12 weeks time as compared in a period of 12 months prior after the initiation of anemia therapy as the average baseline Hb can be 10.1 g/dl during the enrollment and 11.49 g/dl after 12 weeks of treatment. Most of the patients were in stage 2-4 of renal disease with the remaining 25 percent in stage 1 as prior to starting anemia treatment, 24 ml at enrollment and 30 ml after months of anemia therapy.


     


     



     


     


    Kimberly E. Holdener, Melissa Price, Bryan N. Becker, Arjang Djamali, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA EFFECT OF ANEMIA MANAGEMENT ON THE PROGRESSON OF CHRONIC KIDNEY DISEASE


     


     


    Monitoring per week


    Mean HB 12 g/dl


    Epoetin


    anf


    Darbepoetin


     


    3


    1472


    71


     


    6


    882


    65


     


    12


    768


    64


     


     


     


    Hemoglobin > 12 mg/dL


    Nephrologist Managed


    Primary Care Managed


    2.0 percent


    38.6 percent


    Hemoglobin Target Range Met (11-12 mg/dL)


    Nephrologist Managed


    Primary Care Managed


    78 percent


    58 percent


     


     


    Moreover, from the literature base, hemodialysis patients achieving Hb >12 g/dL after switching from human erythropoietin BIW or TIW weekly to once weekly dosing with darbepoetin alfa


     


     



     


    Rutkowski B, Bitterova Z, Ferenczi S et al. Effectiveness of converting


    from itravenous or subcutaneous human erythropoietin to iv darbepoetin alfa (DA) in end stage renal disease patients  on hemodialysis (HD) as presented at American Society of Nephrology Annual Congress, 14–19 November 2006, San Diego, CA, USA


     


     


     



     


    The above figure shows the mean haemoglobin in 95 percent confidence interval as (A) and mean dose of the latter levels (B) after switching from epoetin beta three times weekly to once weekly dosing with either darbepoetin alfa or epoetin beta


     


    Tolman C, Richardson D, Bartlett C et al. Structured conversion from


    thrice weekly to weekly erythropoietic regimens using a computerized


    decision-support system: a randomized clinical study. J Am Soc


    Nephrol 2005; 16: 1463–1470


     


     


    From within CARI dialysis facilities, hemoglobin levels are typically


    measured frequently from weekly to monthly, leading to adjustments in the dose of epoetin, often on the basis of standing anemia management protocols, to maintain the values within some desired range. Hemoglobin has been recommended as the preferred measure


    for anemia management for Alice Springs as there has been some


    concern that the recommended hemoglobin range of 11 to 12 g/dL may be too narrow for routine clinical practice. Ideally, understanding the normal clinical variability of hemoglobin measurements is therefore critical to optimal clinical management aimed at maintaining patient hemoglobin levels within certain range which is reported to be less with hemoglobin, week-to-week and month-to-month variability in hemoglobin levels may be related to epoetin dose adjustments, route of epoetin administration variation in hydration status. Thus, little is known about the clinical variability of hemoglobin measurements in hemodialysis patients. The literature study reported here examines hemoglobin variability under conditions of standard clinical practice


    in hemodialysis patients.


     


     


     



     


    The above points width of hemoglobin range encompassing specified percentages and percentile groups of patient’s hemoglobin values for one month values and rolling averages of 2 to 6 months.


     


     


    Furthermore, CARI (2003), have indicated that, “appropriate target Hb concentration has been debated and is complicated by studies in different population with varying risk factors and different end points. By convention, Hb in the haemodialysis population is measured before dialysis, and thus target Hb values applies to pre-dialysis values. Individual patient who may potentially benefit or suffer according to the Hb level should be considered for anemia therapy”. Also, the protocol advocates the use of CARI guidelines as there concurs with recommendations by some global guidelines such as the ‘European Best Practice Guidelines’.


     


    CARI-guidelines recommendations include


    The recommended haemoglobin concentration for patients with proven or likely significant cardiovascular disease or diabetes mellitus should not exceed 120 g/L (CARI, 2003 p.  12).  The recommended minimum Hb were there has been 110 g/L, Hb concentration between 120 and 140 g/L has a beneficial effect in patients without proven or likely significant cardiovascular disease.  There is no data to suggest the predialysis Hb concentration should rise above 140g/L Aside, recommended haemoglobin concentration for Stage four renal disease patients as targeted from between 120 to 130 g/L, clinical improvement, exercise tolerance and quality of life are considered along with target Hb in an individual patient.


     


    Higher target (Hb, g/dl) are favoured in research literature for:


     


    -      There can be such improvement of certain parameters from within some areas of cardiovascular disease due to renal disease and the optimal quality of life (McMahon et al., 1992; McMahon et al., 1999; McMahon et al., 2000).


    -      Associations between anaemia and risk of every cause and renal death (Madore et al., 1997; Xia et al., 1999, Ma et al., 1999; Locatelli et al., 1998).


    -      Improved exercise capacity as Hb concentration rises in normal subjects (Woodson, 1984) and in patients with progressive renal dysfunction (Clyne and Jogestrand 1992).


    -      Improved quality of life with no serious adverse effects in a random controlled trial (Furuland et al., 2003).


     


    There can be initiation dose of Epoetin alpha as well as Darbepoetin alpha for hemodialysis patients for Alice Springs in Australia   


     


    (Dose rounded) Hb levels g/L


    Weekly Dose


    Epoetin alpha


    Darbepoetin alpha


     


    <70


    120- 160 U/kg


    0.6 – 0.8 mcg/kg


    70-90


    100-120 U/kg


    0.5 – 0.6 mcg/kg


    > 90


    80 – 100 U/kg


    0.4 – 0.5 mcg/kg


     


     


     


     


     


     


     


    What is known and unknown be it on animals or other areas like oncology, renal disease?


    Therapy with human recombinant erythropoietin has been accepted as effective for renal anemia in dialysis patients. However, studies in rats have shown that correcting anemia with EPO may affect the progression of renal dysfunction. In humans, however, the effect of erythropoietin on residual renal function is a matter of controversy. The need to investigate whether the long-term administration of erythropoietin to hemodialysis patients influences residual renal function. Anemic patients at the predialysis stage with a serum creatinine concentration ranging from 2 to 4 mg/dl and a hematocrit  of less than 30 percent were randomly assigned to two groups which consisted of anemic patients not treated with erythropoietin and the anemic patients treated with erythropoietin, treated anemics. Patients with nonsevere or moderate anemia with situation ranging from 2 to 4 mg/dl are recruited as nonanemic controls, untreated nonanemic controls. Blood pressure was controlled to the same degree among the three groups by combined treatment with calcium antagonists and angiotensin-converting enzyme inhibitors (Provenzano, Besarab, Macdougall et al., 2007; Burnier, Demay and Tanghe, 2007). Then, the degree of control of dietary protein and blood pressure and the frequency of angiotensin-converting enzyme inhibitor administration were comparable among the three groups. The primary end point for every patient can possibly be doubling of baseline hemoglobin level which yielded cumulative renal survival rates being gradually noted through time.


     


    There has been core treatment and anemia upon prevention of severe renal disease among patients as the research measure does adhere to amiably eliminate and or reduce exposure to factors which cause imposing value to hemodialysis patients and that for chronic renal disease there approach that involves determined Hb targeted level upon the need of minimizing the incidence as well as prevalence of the agents needed for anemia treatment from within stable blood pressure, from wherein there reduce the number of Alice Spring patients from within risk of developing the kidney disease from determining CARI recommendations as such the early


    detection of renal disease in order to allow prompt and effective anemia intervention to prevent more disease from within posits of assumed renal care and the need to recognize the guideline effectiveness and function process as there becomes fully established. Early detection and effective intervention in the early stages of kidney


    damage are essential to prevent the development of the disease as the CARI guidelines is focusing on management of established disease to prevent progression and delay long term anemia complications from within disability portion. Meanwhile, the need for good management upon assumed kidney replacement therapy not only reduces suffering and death, but also improves quality of life. For instance, in Australia, the CARI execution in Australia are being on credit from the agents as for maintaining Hb levels of the kidney decrease along the patients hit by the incidence of the treated kidney disease pattern being caused by


    analgesic nephropathy in Australia. During the year 2000, Kidney Health Australia and the Australian Society of Nephrology developed the Caring for Australians with Renal Impairment (CARI) Guidelines to guide and improve the management of kidney disease in Australia. The


    CARI guidelines have been well accepted and have extensively influenced practice throughout Australia and New Zealand. Although there have been successes in the past and consistent effort in recent years, the burden imposed by renal disease in Australia has the potential to increase, CARI guidelines are used against available information to illustrate the status of relevant practices to inform


    future policies, strategies and interventions to help reduce the burden of CKD (KHA 2004). The need to improve awareness of kidney disease in the community and among health professionals as there indicated that almost half of respondents were not aware they could reduce their risk of developing kidney disease and had little or no knowledge of how to keep their kidneys healthy (Pfizer Australia and Kidney Health Australia, 2004).  The aim of the CARI Guidelines is to improve the health care and outcomes of paediatric and adult renal patients by helping clinicians and nurses to adhere to evidence-based medical practice as often as possible. It is anticipated that the guidelines will serve as both a valuable educational resource and a means of


    enhancing the quality, appropriateness, consistency and cost effectiveness of renal health care’ (KHA 2005, Hoy et al. 2003). The detailed CARI Guidelines and associated evidence statements can be found on at http://www.kidney.org.au/cari/guidelines.php


     


    The CARI Guidelines recommend that approximately one year is required to optimally prepare a patient and their family/carers for kidney replacement therapy (ANZSN and KHA, 2004). In Australia, referral to a nephrologist less than 90 days prior to the date of initiation of dialysis is regarded as a late referral. Late referral not only limits the patient’s opportunity for selection of dialysis modality and for timely placement of an appropriate dialysis access, but also results in poorer patient survival and reduced likelihood of kidney transplant (Cass et al. 2003; Roderick et al. 2002). The outcome of hemodialysis may be influenced by many factors, particularly the urea reduction ratio, nutritional status and vascular and infective comorbidities connected with dialysis (Excell et al., 2005; Kerr, 2000) from the


    Correspondence to the CARI Guidelines (ANZSN and KHA, 2000).


     


    Research method, design and statistical analysis


    There has to be determining of requirement wherein there evaluates the research outcome as well as barriers to the execution and realization of CARI guidelines (Caring for Australasians with renal impairment), upon hemoglobin/iron management in hemodialysis patients in Alice Springs. The design and setting will be the pointing towards on-site review of hemoglobin management process treating anemia of chronic renal failure at some of the Australian hemodialysis units in Alice Springs at Flynn drive. Alice Spring patients hemoglobin levels need have to be obtained from the Australian Dialysis Registry as there has to be comparison with target levels of hemoglobin into CARI guidelines. For the statistical analysis, it can be that the using of Alice Springs population estimates based on the latest CARI census, the ideal calculation of the such average yet quarterly incidence of anemia of hemodialysis patients because of renal failure allowing an audit of target hemoglobin levels from the renal unit at Alice Springs. The use of CARI estimates of the Australian population, derived using demographic information on the place of registered residence. The CARI estimates are to be adjusted for net Census undercount and non-response to the census question about prevalence of anemia in hemodialysis patients. The use of standardization to calculate the age as well as sex incidence ratio with 75 percent confidence intervals for the Spring. Thus, rates for total Alice Spring population are used as the reference meaning, the standardized incidence ratio equals incidence in Alice Spring as divided by incidence in whole Australia population, and adjusting differences in the age and sex composition as the statistical analysis are performed through charts, figures and tables.


     


     


    Research sample, recruitment, participants and settings


     


    The research study will review be identifying database information for a maximum sample size of 160. This is the population of stable hemodialysis patients receiving treatment at Flynne drive renal dialysis unit, Alice Springs. No names will be collected however hospital registration numbers will be used for data matching. Identifying information will be removed once data analysis has been completed. Only people with access to data during the usual course of their clinical role will be involved in any data collection.


    Participants:


    Charts of all patients meeting the following criteria will be audited, Stable hemodialysis patients receiving hemodialysis in Alice Springs, Over 18 yrs, receive either epoetin or darbepoetin for treatment of anemia of renal failure, have baseline hemoglobin levels of <12g/dl which is the target hemoglobin levels for anemia according to CARI guidelines.


     


    Benefits:


    The results may help determine effectiveness of epoetin and darbepoetin on hemoglobin levels over time in the patient population including determining what proportion of Alice Springs patients achieved their targeted hemoglobin levels compared to CARI guidelines.  There can be some associated risks for the realization of the research project, as such there will be no change in usual practice and no additional risks beyond those of usual clinical practice. Renal anemia database is located within the renal dialysis unit and contains information on patients’ hemoglobin levels, epoetin and drabepoetin doses and any changes in the patients’ treatment.


    Monitoring:


    Baseline hemoglobin levels of all stable hemodialysis patients on either epoetin or darbepoetin at the beginning of the study will be accessed through the renal anemia database and thereafter hemoglobin levels will be monitored monthly for 12 weeks and any changes in the doses of epoetin and drabepoetin. No patients will be recruited for this retrospective chart audit.


     


    Results, discussion, limitations and recommendations


    There was considerable variability among the units in achievement of


    haemoglobin targets, from within twenty eight to thirty one percent of patients achieving haemoglobin targets at around 110–120 g/L, as the implementation barriers did imply certain lack of knowledge, lack of awareness of and or trust into the CARI guideline, inability to implement the guideline, and inability to agree on a uniform unit protocol. Factors associated with achieving the CARI guideline targets included nurse-driven anemia management protocols, use of hemoglobin management decision aid, few nephrologists per dialysis unit and a proactive as rather than reactive range of the protocol. Furthermore, there reveals significant variation in the incidence of anemia of renal diseases among Alice Springs Australians. The areas of highest incidence can be about 2000 cases per ten years time, in the areas of Alice Springs Flynn Drive, Australia. Thus, some of the standardized incidence ratio for anemia of chronic renal failure have ranged from less than two in Alice Springs, as there were certain hemodialysis patients identified as part of indigenous group in Alice Springs, Australia from the three month period. Most hemodialysis patients in Alice Springs should travel near or far in order to access and receive CARI services into the renal care unit of Alice Springs wherein they have treatments for anemia upon utilizing the two options for the treatment along with guidelines effectiveness and usage to patients in need of the desired medication. Meanwhile, it can be that, the Alice Springs in Australia experience with Darbepoetin reveals that this long­ acting erythropoiesis stimulating agent is effective and safe for the treatment of anemia in patients on hemodialysis. It is more con­venient for dosing than short-acting erythro­poietin. Predialysis stages of chronic kidney disease and peritoneal dialysis patients may benefit even more from the extended periods between doses. There is a decrease in the dose over time and savings are expected with darbepoetin over time relative to short acting erythropoietin.


     


    The meaning for hemodialysis patients in Alice Spring


    Accordingly, the use of epoetin and darbepoetin is one way to treat anemia caused by chemotherapy when used according to the FDA-approved label. Treatment with one of these drugs can help patients avoid red blood cell transfusions, but may also raise the risk of blood clots, which is a serious health risk in people with cancer. Other treatments may be used for people with anemia who are receiving chemotherapy, and it is important for the doctor to rule out other causes of anemia and the need to consult the health team and physician about the cause of the anemia and recognize the best way to diagnose and treat it. There has been variability in achievement of hemoglobin level targets, despite the availability of CARI practice guideline as amiably explained through the variability in situations and processes of renal disease care for achieving and maintaining adequate blood level as well as stable parameters along the way.


     


    For the recommendation, the epoetin and darbepoetin are equal in terms of effectiveness and safety when used to treat kidney disease related anemia. These drugs may also be considered for some patients with low-risk myelodysplastic syndrome, a type of disorder of the bone marrow that may cause anemia. However, epoetin and darbepoetin should not be used to treat anemia in patients with renal failure who are no longer receiving hemodialysis. The physician may choose to begin treatment earlier, when the hemoglobin level is between 10 g/dL and 12 g/dL, for patients with other medical conditions affected by anemia or those who have difficulties performing regular daily activities. The doses of these drugs may need to be adjusted over time, so that the hemoglobin level remains high enough for the patient to avoid a blood transfusion but remains under 12 g/dL. Levels higher than 12 g/dL, when produced with these drugs, may create serious health risks. For patients with normal levels of hemoglobin higher than 12 g/dL do not have these same risks. Doctors and patients should weigh the risks and benefits of these drugs for patients at high risk for developing blood clots. Risk factors includes blood clot, surgery, limited activity and some types of kidney centered therapy. Thus, if the hemoglobin levels are not rising after several weeks of treatment with one of these drugs, the doctor may consider increasing the dose, as recommended in the labeling of the drug and if hemoglobin levels still do not rise after another week, then such anemia intervention must be stopped.


     


     


     


    Timeline                                                              Budget                                              


     


    25 -30 $


     


     


    10-15 $


     


    20-40 $


     


    Search for Related Literature


     


     


     


    Selection of the  Topic


     


     


     


    Definition of the Problem


     


     


     


    Development of the Objectives


     


     


     


    Selection of Methodology


     


     


     


    Check the availability of resources


     


     


     


    Verify the accessibility of the resources


     


     


     


    Write the draft of the proposal


     


     


     


    Prepare interview schedule


     


     


     


    Secure adviser’s approval


     


     


     


    Do the needed revisions


     


     


     


    Test research tool validity


     


     


     


    Select the study sample


     


     


     


    Conduct research proper


     


     


     


    Administer research tools


     


     


     


    Do the assessment techniques


     


     


     


    Gather and analyze results


     


     


     


    Do the necessary data presentation


     


     


     


    Interpret findings


     


     


     


    Preparation of the final report


     


     


     


    Formulation of conclusions and recommendations


     


     


     


    Preparation of the table of content, appendices


     


     


     


    Editing and Final Formatting


     


     


     


    Printing


     


     


     


     


     


     


     


     


     


     


     


     


     


     


    References


     


     


    ANZSN & KHA (Australian and New Zealand Society of Nephrology & Kidney Health Australia) 2000. The Caring for Australians with Renal Impairment (CARI) Guidelines (draft): Dialysis adequacy, in Dialysis guidelines. Adelaide: Australian and New Zealand Society of Nephrology and Kidney Health Australia. Viewed 8 June 2005


     


    ANZSN & KHA 2004. The Caring for Australians with Renal Impairment (CARI) Guidelines (draft): Early referral of pre-ESRD patients, in Prevention of progression of kidney disease. Adelaide: Australian and New Zealand Society of Nephrology and Kidney Health Australia. Viewed 8 June 2005


     


    Bradbury BD, Fissell RB, Albert JM et al. Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Clin J Am Soc Nephrol 2007; 2: 89–99


     


    Burnier M, Demay J, Tanghe A. Less frequent dosing of erythropoiesis-stimulating agents may result in cost savings in European dialysis centers. J Am Soc Nephrol 2007


     


    CARI. (2003). The Caring for Australians with Renal Impairment (CARI) Guidelines. Retrieved: January 13th 2006, from http://www.kidney.org.au


     


    Carrera F, Macdougall IC. Hemoglobin targets: the jury is still out. Clin Nephrol 2008; 69: 8–9 in Binocrit, R. Sm, PC. Sandoz, 2008. http://www.emea.europa.eu/


     


    Cass A, Cunningham J, Snelling P et al. 2003. Late referral to a nephrologist reduces access to renal transplantation. American Journal of Kidney Diseases 42(5):1043–9.


     


    Curtis BM, Ravani P, Malberti F et al. 2005. The short- and long-term impact of multidisciplinary clinics in addition to standard nephrology care on patient outcomes. Nephrology Dialysis Transplantation 20(1):147–54.


     


    Clyne, N., & Jogestrand, T. (1992). Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients. Nephron, 60, 390-396.


     


    Furuland, H., Linde, T., & Ahlmen, J. (2003). A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrology Dialysis Transplantation, 18, 353-361.


     


    Hoy WE, Wang Z, Baker PR & Kelly AM 2003. Reduction in natural death and renal failure from a systematic screening and treatment program in an Australian Aboriginal community. Kidney International Suppl. 83:S66–73.


     


    Kerr P 2000. Haemodialysis. In: Disney APS (ed.). ANZDATA Registry report 2000. Adelaide: Australia and New Zealand Dialysis and Transplant Registry.


     


    KHA 2005. The CARI guidelines. KHA, Melbourne. Viewed 22 August 2005, <http://www.kidney.org.au/?section=2&subsection=16>.


     


    Locatelli, F., Conte, F., & Marcelli, D. (1998). The impact of hematocrit levels and erythropoietin treatment on overall and cardiovascular mortality and morbidity-the experience of the Lombardy Dialysis Registry. Nephrology Dialysis Transplantation, 13, 1642-1644.


     


    Locatelli F, Pisoni RL, Combe C et al. Anaemia in haemodialysis patients of five European countries: association with morbidity andmortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2004; 19: 121–132


     


    Ma, J., Ebben, J., Xia, H., & Collins, A. (1999). Hematocrit level and associated mortality in  hemodialysis patients. Journal of American Society of Nephrology, 10, 610-619.


     


    Madore, F., Lowrie, E., & Brugnara, C. (1997). Anaemia in haemodialysis patients: variables affecting this outcome predictor. Journal of American Society of Nephrology, 8,1921-1929


     


    Macdougall IC. The management of anaemia in chronic kidney disease current and future issues. Eur Ren Genitourin Dis. 2006;35-36.


     


    Macdougall IC, Eckardt KU. Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia. Lancet. 2006;368:947-95


     


    Mann J, Kessler M, Villa G et al. Darbepoetin alfa once every 2 weeks for treatment of anemia in dialysis patients: a combined analysis of eight multi center trials. Clin Nephrol 2007; 67: 140–148


     


    McMahon, L., Johns, J., & McKenzie, A. (1992). Hemodynamic changes and physical performance at comparative levels of haemoglobin after long-term treatment with recombinant erythropoietin. Nephrology Dialysis Transplantation, 7, 1199-1206.


     


    McMahon, L., McKenna, M., & Sangkabutra, T. (1999). Physical performance and associated electrolyte changes after haemoglobin normalization: a comparative study in haemodialysis patients. Nephrology Dialysis Transplantation, 14, 1182-1187


     


    McMahon, L., Mason, K., & Skinner, S. (2000). Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrology Dialysis Transplantation, 15, 1425-1430.


     


    Melnikova I. Anaemia therapies. Nat Rev Drug Discov. 2006;5:627-628. Abstract


     


    Mendelssohn DC 2005. Coping with the CKD epidemic: the promise of multidisciplinary team-based care. Nephrology Dialysis Transplantation 20(1):10–2.


     


    NPHP (National Public Health Partnership) 2001. Preventing chronic disease: a strategic framework. Melbourne: NPHP.


     


    Nissenson A, Krishnan M, Liu W, et al. Hemoglobin (Hb) variability does not differ between hemodialysis (HD) patients treated with epoetin alfa and darbepoetin alfa. Program and abstracts of the American Society of Nephrology Annual Meeting; November 14-19, 2006; San Diego, California. Abstract TH-PO360.


     


    Pfizer Australia and Kidney Health Australia 2004. Pfizer Australia Health Report. Issue no. 4. West Ryde, NSW: Pfizer Australia.


     


     


    Phrommintikul A, Haas SJ, Elsik M et al. Mortality and target haemoglobin concentrations in anaemia patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007; 369: 381–388


     


    Provenzano R, Besarab A, Macdougall IC et al. The continuous erythropoietin receptor activator (C.E.R.A.) corrects anaemia at extended administration intervals in patients with chronic kidney disease not on dialysis: results of a phase II study. Clin Nephrol 2007; 67: 306–317


     


    Rao M, Pereira BJG. Prospective trials on anemia of chronic kidney disease: the trial to reduce cardiovascular events with Aranesp therapy. Business Briefing: North Am Pharmacol 2006:97-10


     


    Rastogi A, Nissenson AR. New approaches to the management of anemia of chronic kidney disease: beyond Epogen and Infed. Kidney Int Suppl. 2006;104:S14-S16. Abstract


     


    Regidor DL, Kopple JS, Lovesdy CP et al. Associations between changes in hemoglobin and administered erythropoiesis stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol 2006; 17: 1181–1191


     


    Roderick P, Jones C, Drey N et al 2002. Late referral for end-stage renal disease: a region wide survey in the south west of England. Nephrology Dialysis Transplantation 17:1252–9


     


    Simon DB, McLean R, Halloran S, et al. Improving outcomes in anemia management in a community CKD center: conversion from epoetin alfa to darbepoetin alfa. Program and abstracts of the American Society of Nephrology Annual Meeting; November 14-19, 2006; San Diego, California. Abstract SA-PO215.


    Woodson, R. (1984). Haemoglobin concentration and exercise capacity. American Rev Respiratory Disease, 129, S72-S75.


     


    Xia, H., Ebben, J., Ma, J., & Collins, A. (1999). Hematocrit levels and hospitalisation risks in hemodialysis patients. Journal of American Society of Nephrology, 10, 1309-1316.


     


     


     



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