Anemia In Predialysis Patients Research Articles

Assessment of Erythropoietin Efficacy in Treatment of Anemia in Pre-dialysis Chronic Kidney Disease Patients

Background: Anemia is the most frequent condition in patients suffering from chronic renal disease. Iron supplements are commonly prescribed for these patients using oral and intravenous iron with or without erythropoietin therapy. Objectives: This study aimed at comparing the efficacy of IV iron versus oral iron in raising hemoglobin levels in predialysis chronic kidney disease (CKD) patients. Patients and Methods: A prospective cohort study that was conducted in Met-Ghamr Hospital of Nephrology and Urology from February 2019 to July 2019. The study included 50 CKD patients with anemia in the pre-dialysis stage. Group 1 consisted of 25 patients that were given IV iron while the 25 patients of group 2 were given oral iron. Both groups were monitored for 4 months for changes in hemoglobin levels and side effects. After the initial 4 months, patients in both groups who did not have a sufficient hemoglobin response to iron supplementation were prescribed an additional erythropoiesis-stimulating agent (ESA) with monitoring of hemoglobin response for the consequent 2 months. Results: We found a significant difference in the hemoglobin response between the two sets of patients in favor of the IV route after 4 months. We also found the safety profile of both routes to be comparable. After 4 months, the patients that received additional dose of Epoetin alfa (4000 IU/week for 2 months) showed a significant rise in hemoglobin level over the next 2 months compared to patients who did not receive the additional dose. Conclusion: We concluded that intravenous iron supplement is better than oral iron supplement in correction of anemia in pre-dialysis patients.

Association between serum magnesium and anemia in patients with chronic kidney disease.

An inverse association was shown between serum magnesium levels and anemia in the general population. However, limited information is available about the association between serum magnesium level and anemia in the patient population with chronic kidney disease. We aimed to investigate the relationship between hypomagnesemia and anemia in pre-dialysis patients with chronic kidney disease stage 3-5. This cross-sectional retrospective study included 213 chronic kidney disease patients with an estimated glomerular filtration rate of 60mL/min and below. Laboratory and demographic data of outpatients were collected in January 2018-January 2019. Patients with a magnesium level below 1.9mg/dL were accepted as the hypomagnesemia group. Serum magnesium level of 62 (29.1%) of these patients were below 1.9mg/dL. Compared with normomagnesemic patients, hypomagnesemic patients had lower mean hemoglobin values (11.3g/dL vs. 12.7g/dL, P < 0.001), proton-pump inhibitor usage rates were significantly higher (33.9% vs. 17.2%, P = 0.008) and the median urine protein/creatinine ratio was found to be significantly higher (1017.5mg/gCr vs. 536mg/gCr, P = 0.045). In the multivariate analysis, the use of hemoglobin (OR 0.634; 95% CI 0.505-0.795; P < 0.001) and proton-pump inhibitor (OR 2.670; 95% CI 1.113-6.318; P = 0.025) were independent predictors of hypomagnesemia. Hypomagnesemia is a common electrolyte disorder in pre-dialysis CKD patients. In this patient group, anemia is independently associated with hypomagnesemia.

Iron deficiency across chronic kidney disease stages: Is there a reverse gender pattern?

In non-dialysis chronic kidney disease patients, looking for iron deficiency is highly variable in practice and there is a great variability regarding the cutoffs used to treat iron deficiency. The aim of this study is to investigate the degree of iron deficiency in non-dialysis chronic kidney disease patients on erythropoiesis-stimulating agents. We included all non-dialysis chronic kidney disease patients that applied to the Lebanese Ministry of Public Health for erythropoiesis-stimulating agents’ coverage during a 5-month period. Iron requirement was assessed based on two guidelines’ target-to-treat cutoffs: 1-ferritin <100 ng/ml and/or TSAT < 20% (KDOQI 2006), 2- ferritin ≤500 ng/ml and TSAT ≤30% (KDIGO 2012). A total of 238 CKD patients were included over 5 months. All patients had a ferritin level in their record and 64% had an available TSAT. Median age was 71.0 (59.8–79.3) years and 61.8% were female. All had an eGFR<60 ml/min. The proportion of patients found to require iron therapy ranged between 48 and 78% with a trend towards higher values when using KDIGO-based criteria. Using ANCOVA test, inverse normal transformations of ferritin and TSAT showed a reverse pattern between men and women with women being more iron deficient in the early stage. Iron deficiency is highly prevalent in non-dialysis chronic kidney disease patients on erythropoiesis-stimulating agents’ therapy. These findings reflect a lack in effective iron supplementation when managing anemia in pre-dialysis patients, especially in men at advanced stages. Renal societies should spread awareness about iron deficiency screening in those patients.

Short-acting erythropoiesis-stimulating agents for anaemia in predialysis patients.

The benefits of erythropoiesis-stimulating agents (ESA) for chronic kidney disease (CKD) patients have been previously demonstrated. However, the efficacy and safety of short-acting epoetins administered at larger doses and reduced frequency as well as of new epoetins and biosimilars remains uncertain. This review aimed to evaluate the benefits and harms of different routes, frequencies and doses of epoetins (epoetin alpha, epoetin beta and other short-acting epoetins) for anaemia in adults and children with CKD not receiving dialysis. We searched the Cochrane Kidney and Transplant Specialised Register to 12 September 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We included randomised control trials (RCTs) comparing different frequencies, routes, doses and types of short-acting ESAs in CKD patients. Two authors independently assessed study eligibility and four authors assessed risk of bias and extracted data. Results were expressed as risk ratio (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model. We identified 14 RCTs (2616 participants); nine studies were multi-centre and two studies involved children. The risk of bias was high in most studies; only three studies demonstrated adequate random sequence generation and only two studies were at low risk of bias for allocation concealment. Blinding of participants and personnel was at low risk of bias in one study. Blinding of outcome assessment was judged at low risk in 13 studies as the outcome measures were reported as laboratory results and therefore unlikely to be influenced by blinding. Attrition bias was at low risk of bias in eight studies while selective reporting was at low risk in six included studies.Four interventions were compared: epoetin alpha or beta at different frequencies using the same total dose (six studies); epoetin alpha at the same frequency and different total doses (two studies); epoetin alpha administered intravenously versus subcutaneous administration (one study); epoetin alpha or beta versus other epoetins or biosimilars (five studies). One study compared both different frequencies of epoetin alpha at the same total dose and at the same frequency using different total doses.Data from only 7/14 studies could be included in our meta-analyses. There were no significant differences in final haemoglobin (Hb) levels when dosing every two weeks was compared with weekly dosing (4 studies, 785 participants: MD -0.20 g/dL, 95% CI -0.33 to -0.07), when four weekly dosing was compared with two weekly dosing (three studies, 671 participants: MD -0.16 g/dL, 95% CI -0.43 to 0.10) or when different total doses were administered at the same frequency (four weekly administration: one study, 144 participants: MD 0.17 g/dL 95% CI -0.19 to 0.53).Five studies evaluated different interventions. One study compared epoetin theta with epoetin alpha and found no significant differences in Hb levels (288 participants: MD -0.02 g/dL, 95% CI -0.25 to 0.21). One study found significantly higher pain scores with subcutaneous epoetin alpha compared with epoetin beta. Two studies (165 participants) compared epoetin delta with epoetin alpha, with no results available since the pharmaceutical company withdrew epoetin delta for commercial reasons. The fifth study comparing the biosimilar HX575 with epoetin alpha was stopped after patients receiving HX575 subcutaneously developed anti-epoetin antibodies and no results were available.Adverse events were poorly reported in all studies and did not differ significantly within comparisons. Mortality was only detailed adequately in four studies and only one study included quality of life data. Epoetin alpha given at higher doses for extended intervals (two or four weekly) is non-inferior to more frequent dosing intervals in maintaining final Hb levels with no significant differences in adverse effects in non-dialysed CKD patients. However the data are of low methodological quality so that differences in efficacy and safety cannot be excluded. Further large, well designed, RCTs with patient-centred outcomes are required to assess the safety and efficacy of large doses of the shorter acting ESAs, including biosimilars of epoetin alpha, administered less frequently compared with more frequent administration of smaller doses in children and adults with CKD not on dialysis.

Prevalence and management of anemia in pre-dialysis Malaysian patients: A hospital-based study.

Anemia, a common complication of chronic kidney diseases (CKD), is involved in significant cardiovascular morbidity. Therefore, the objective of our study was to investigate the prevalence and severity of anemia in pre-dialysis patients, as well as to determine the predictors of anti-anemic therapy. A retrospective, observational study was conducted on adult pre-dialysis patients receiving treatment at the Hospital Universiti Sains Malaysia from January 2009 to December 2013. A total of 615 eligible cases were included. The mean age of patients was 64.1±12.0 years. The prevalence of anemia was 75.8%, and the severity of anemia was mild in 47.7% of the patients, moderate in 32.2%, and severe in 20%. Based on morphological classification of anemia, 76.9% of our patients had normochromic-normocytic anemia whereas 21.8 and 1.3% had hypochromic-microcytic anemia and macrocytic anemia, respectively. Oral iron supplements were prescribed to 38.0% of the patients and none of the patients was given erythropoietin stabilizing agents (ESA) or intravenous iron preparations. In logistic regression, significant predictors of anti-anemic preparation use were decreased hemoglobin and hematocrit, and advanced stages of CKD. The results of the present study suggest that the prevalence of anemia in pre-dialysis patients is higher than currently accepted and it is found to be correlated with renal function; prevalence increases with declined renal function. An earlier identification as well as appropriate management of anemia will not only have a positive impact on quality of life but also reduce hospitalizations of CKD patients due to cardiovascular events.

Subcutaneous C.E.R.A. for the Treatment of Chronic Renal Anemia in Predialysis Patients.

We investigated the efficacy, safety and tolerability of once-monthly administration of C.E.R.A. in erythropoiesis stimulating agents (ESAs) naive predialysis patients with CKD for anemia treatment. Single arm, open label study. A total of 75 patients (mean (SD) age was 52.8 (16.4) years, 76.0% were female) were included in this study conducted between 12 August 2008 and 30 October 2009 in 9 centers across Turkey. The mean change in Hb concentration (g/dL) between baseline (week 0) and the efficacy evaluation period (EEP) was the primary efficacy parameter evaluated in three consecutive periods including a dose titration period (DTP; with initial 1.2 μg/kg dose of C.E.R.A., subcutaneously, 28 weeks), EEP (8 weeks) and a long-term safety period (16 weeks). Our analysis revealed an improvement in Hb levels from baseline value of 9.4 (0.4) g/dL to time adjusted average level of 11.4 (0.7) g/dL in EEP in the per protocol (PP) population and from 9.3 (0.5) g/dL to 11.1 (1.0) g/dL in intent-to-treat (ITT) population. Mean (SD) change in Hb levels from baseline to EEP was 2.0 (0.7) g/dl in the PP population (primary endpoint) and 1.7 (1.1) g/dL in the ITT population. The percentage of patients whose Hb concentrations remained within the target range of 10.0-12.0 g/dL throughout the EEP was 43.9% (95% CI: 28.5-60.3%) in the PP population and 38.7% (95% CI: 27.6% to 50.6%) in the ITP population. A total of 206 adverse events (AE) were reported in 77.0% of patients with hypertension (20%) as the most frequent AE. Once-monthly subcutaneous C.E.R.A. administration is effective and safe in the treatment of anemia in pre-dialysis patients with CKD, who are not currently treated with ESAs.

Subcutaneous C.E.R.A. for the Treatment of Chronic Renal Anemia in Predialysis Patients

Subcutaneous C.E.R.A. for the Treatment of Chronic Renal Anemia in Predialysis Patients

Effect of anemia on cardiac disorders in pre-dialysis patients immediately before starting hemodialysis

Anemia is a common complication of patients with chronic kidney disease (CKD), which not only lowers their quality of life but also potentially causes cardiovascular diseases such as congestive heart failure and coronary heart disease, and accelerates the progression of renal dysfunction. Pre-dialysis patients were assigned to groups A, B, C or D based on hemoglobin levels of ≤ 8.9 (n = 48), 9.0-9.9 (n = 63), 10-10.9 (n = 53), and ≥ 11.0 g/dL (n = 39), respectively. Cardiac function was estimated using echocardiography to clarify the relationship between anemia and cardiac disorders in patients with CKD immediately before starting hemodialysis. Left ventricular ejection fraction (LVEF) was significantly higher in group D than in groups A and B. The fractions with an LVEF of less than 50% were 16.7, 4.8, 1.9, and 0% in groups A, B, C, and D, respectively. Posterior wall thickness was statistically thicker and the deceleration time of the early diastolic wave was longer in groups A and B, respectively, than in groups C and D. The left ventricular mass index in group D was significantly lower than in any other groups. Anemia in pre-dialysis patients with CKD is a probable cause of impaired left ventricular systolic function and progressive left ventricular hypertrophy. Our results suggest that Hb levels should be maintained at >11 g/dL by EPO administration from the perspective of protecting cardiac function, although the upper limit of the target Hb level was undetermined.

Validation of erythropoietin use data on Medicare's End-Stage Renal Disease Medical Evidence Report

Data from Medicare's End-Stage Renal Disease Medical Evidence Report (Form 2728) suggest that underuse of erythropoiesis-stimulating agents (ESAs) may be contributing to anemia in predialysis patients. However, the data quality of Form 2728 is not known. ESA prescription records were confirmed in Department of Veterans Affairs (VA) data sets and/or ESA claims in Medicare files and compared with data collected on Form 2728 among 8,033 veterans who initiated dialysis in 2000 and 2001 and were eligible for both VA and Medicare coverage in the 12 months preceding dialysis initiation. Among the cohort, predialysis ESA use was found in 4% (n = 323) more veterans by VA/Medicare data sets (n = 2,810) than by Form 2728 (n = 2,487). With the use of VA/Medicare data sets (gold standard), the accuracy of Form 2728 for predialysis ESA use was sensitivity 57.0%, specificity 83.1%, positive predictive value 64.5%, negative predictive value 78.2%, and kappa coefficient 0.41. Sensitivity for reported predialysis ESA use on Form 2728 was lowest among veterans who were female and nonwhite, of low socioeconomic status, and with anemia or other comorbid illnesses. The poor sensitivity and specificity of predialysis ESA use data on Form 2728 raise concerns about the validity of previous reports and study findings. Investigators should recognize these shortcomings and the introduction of possible bias in future research and reports.

High Prevalence of Anemia in Predialysis Patients in Enugu, Nigeria

Anemia is common in chronic kidney disease (CKD) and contributes to adverse clinical outcomes. African Americans have a 3-fold increased likelihood of anemia compared with whites. Little is known about the prevalence of anemia of CKD among Nigerians. This study investigated the prevalence of anemia in all stages of CKD and the relationship of anemia to the etiology of CKD. Consecutive predialysis patients in all stages of CKD from 2004 to 2008 at first evaluation in a tertiary hospital renal clinic, and sex and age matched control subjects, were studied. Demographic data, and results of biochemical and hematologic indices cause of CKD were extracted from patients' records and analyzed using SPSS version 15. All tests were two-tailed, and P&lt;0.05 taken to be statistically significant. Three hundred and sixty-four patients (mean age 44.8∓14.8 years) and 143 control subjects (mean age 43.52∓12.00 years, P=0.35) were analyzed. Overall 77.5% of CKD patients and 11.9% (P&lt;0.001) of control subjects had anemia defined as hemoglobin less than 12 g/dL. Anemia increased progressively with declining GFR with mean hemoglobin concentration of 12.91∓1.35 g/dL, 12.14∓1.96, 10.57∓2.42, 8.84∓2.19 and 7.33∓1.74 for CKD stages 1 to 5, respectively. Multiple regression analysis showed chronic glomerulonephritis (CGN), human immunodeficiency/retroviral disease, collagen vascular disease and chronic pyelonephritis predicted anemia in CKD. Anemia was seen at all stages of CKD and progressed from CKD stage 1 to 5. Anemia was worse in women for all stages of CKD.

Prevalence, etiology, and consequences of anemia and clinical and economic benefits of anemia correction in patients with chronic kidney disease: An overview

The prevalence of chronic kidney disease (CKD) and anemia in the United States, classification scheme for CKD, definition of anemia, etiology and consequences of anemia in patients with CKD, and the clinical and economic benefits of correcting anemia are described. Approximately 20 million people in the United States population have CKD, and 2-4 million of these may also have anemia, which often goes undetected and untreated. Patients with CKD are now classified into five stages based on the degree of kidney function impairment. Here, anemia is caused by insufficient erythropoietin production, and may occur as early as stage 3 CKD. Potential consequences of anemia include cognitive impairment, angina, and the cardiorenal anemia syndrome, a triad of worsening anemia, worsening CKD, and worsening congestive heart failure. Treatment of anemia in predialysis patients with stage 2-4 CKD may slow renal disease progression and improve energy, work capacity, health-related quality of life, and cardiac function. Optimizing the hemoglobin or hematocrit value before initiating dialysis may reduce mortality. Anemia contributes to significant healthcare costs associated with CKD. Substitution of the subcutaneous route of administration for the intravenous route of administration for epoetin alfa can reduce drug acquisition and healthcare costs, the two largest components of healthcare costs in CKD patients. Efforts to slow the progression of CKD could also have a substantial impact on hospitalizations and costs. Correcting anemia has the potential to improve clinical and economic outcomes in patients with CKD.

Individualizing anaemia treatment: a discussion of case histories

Current guidelines give evidence-based advice on how best to manage anaemia in patients with renal disease, but these guidelines do not consider individual patient needs, so tailoring anaemia management to each patient still remains a challenge for the treating physician. Two case studies are described that illustrate some of the key factors that need to be considered. The first case emphasizes that haemoglobin (Hb) targets recommended in current guidelines may not suit all patients. The patient had been stably maintained on subcutaneous epoetin therapy with an average Hb concentration of >13.0 g/dl because he developed angina symptoms when his Hb level fell to 12.2 g/dl. Iron deficiency was identified as the likely cause of falling Hb in this patient. After the patient's iron supplementation was increased, his Hb level was normalized back to >13.0 g/dl without increasing the epoetin dose, and the angina symptoms were resolved. The second case involved a pre-dialysis patient with diabetes, who required a higher dose of epoetin after beginning concomitant antihypertensive treatment with an angiotensin-converting enzyme inhibitor. Previously, the treatment of renal anaemia in pre-dialysis patients has not been the focus of attention. Two ongoing randomized controlled trials have been designed to study early initiation of epoetin treatment in pre-dialysis patients and will provide much needed information in this area.

TOTAL DOSE INFUSION IRON DEXTRAN THERAPY IN PREDIALYSIS CHRONIC RENAL FAILURE PATIENTS

Background: Intravenous iron therapy is now the standard modality of iron supplementation in hemodialysis patients, but its role in predialysis chronic renal failure patients is less well established. The efficacy and safety of intravenous iron dextran as a total dose infusion in predialysis chronic renal failure patients, not receiving erythropoietin was assessed in this study. Methods: Fifty-six predialysis chronic renal failure patients with anemia, not receiving erythropoietin were included in the study, after obtaining informed consent. Hemoglobin, serum creatinine, creatinine clearance rate and serum ferritin were assessed in all the patients at baseline. Iron dextran in a dose of 1 g dissolved in 500 mL normal saline was administered to all patients as a total dose infusion over 6 h after a prior test dose. Patients were kept in hospital under observation for at least 24 h. All the parameters were repeated in all the patients at 12 weeks and in 21 patients at 1 year. Results: The mean hemoglobin (g/dL) in the patients at baseline and at 12 weeks was 8.28 ± 0.57 and 9.22 ± 0.44 respectively (p<0.001). The mean serum ferritin (ng/mL) increased from 29.73 ± 9.38 at baseline to 218.43 ± 15.66 at 12 weeks (p< 0.00001). The mean ferritin value in the 21 patients at 1 year was 136.5 ± 23.4 (p<0.01). There were no major adverse events and only minor side effects were observed in 4.9% patients. Conclusion: Iron dextran as a total dose infusion corrects anemia in predialysis patients and is an effective method to replenish iron stores. The effect on serum ferritin are evident even at 1 year after the total dose infusion.

Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients.

Treatment with recombinant human erythropoietin (rHu EPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHu EPO use in pre-dialysis patients. There is a concern that rHu EPO may accelerate the deterioration in renal function, however the opposing view is that if rHu EPO is as effective in pre-dialysis patients that by improving the patients sense of well-being the onset of dialysis could be delayed. To assess the effects of rHu EPO use in pre-dialysis patients with renal anaemia. We searched MEDLINE (1980 to May Week 3 2001), EMBASE (1984 to Week 24 2001), BIOSIS (1985 to January 1997), CINAHL (1982 to October 1997), The Cochrane Library (Issue 1, 1997), CHEMABS (1984 to November 1996), SIGLE (1980 to June 1996), CRIB (10th edition, 1995), UK NRR (14TH consolidation, September 1996), RSC ( 1980 to February 1997), HealthSTAR (1995 to October 1997), IBSS (1984 to July 1997), NEED (July 1997) and reference lists of relevant articles. We contacted biomedical companies and investigators in the field and we hand searched Kidney International (including all supplements but excluding all conference proceedings except for 1994) July 1983 to May 1997 inclusive. The internet was also searched on: August 1997. We had also identified some studies from a previous broad search for all randomised controlled trials (RCTs) relevant to the management of end-stage renal disease. Date of the most recent search: June 2001. RCTs or quasi-RCTs comparing the use of rHu EPO with no rHu EPO or placebo in pre-dialysis patients. Only published data were used. Data were abstracted by a single investigator onto a standard form. A sample of the data abstracted was double-checked by another reviewer. The data abstracted were relevant to the predetermined outcome measures. Some authors were contacted to clarify how patients were allocated to groups. All authors from included studies were contacted for missing information. Twelve studies with a total of 232 participants met the inclusion criteria and where possible data from these were summated by meta-analyses (Peto's Odds Ratio (OR) and Weighted Mean Difference (WMD)). The majority of the trials included small numbers and were of short duration (8-10 weeks) with the exception of three trials. There was a marked improvement in haemoglobin (mean difference 2.3g/dL, 95% CI 1.37 to 3.23) and haematocrit (WMD 9.92%, 95% CI 8.78 to 11.05) with the treatment and a decrease in the number of patients requiring blood transfusion (OR 0.25, 95% CI 0.09 to 0.69). The data from all studies which reported quality of life or exercise capacity demonstrated an improvement in the rHu EPO group. None of the measures of progression of renal disease (when a summary statistic was calculated) demonstrated a statistically significant difference. Though the requirement for antihypertensive treatment appears to be increased by rHu EPO (OR 1.84, 95% CI 1.02 to 3.32), there was no other statistically significant increase in adverse events. Based on the limited current evidence, decisions therefore have to be made on whether the putative benefits in terms of quality of life identified in the review are worth the extra costs of pre-dialysis rHu EPO. This review has shown that treatment with rHu EPO in pre-dialysis patients corrects anaemia and avoids the requirement for blood transfusions. There are also improvements in quality of life and exercise capacity. There may be increased hypertension. Most of the trials were not of sufficient duration to assess the effects of rHu EPO on progression of renal disease. In the long term, questions still remain about whether pre-dialysis rHu EPO either speeds up or delays the onset of dialysis. Thus there is insufficient evidence on the total costs and benefits of treating pre-dialysis patients with rHu EPO.

Efficacy and tolerability of recombinant human erythropoietin treatment in pre-dialysis patients: Results of a multicenter study

Chronic renal failure is characterized by a normochromic normocytic anemia, the severity of which generally increases during progression toward uremia. The purpose of the study was to evaluate the efficacy and safety of recombinant human erythropoietin (rHu-EPO) given subcutaneously (s.c.), the dose required to reach and maintain Hb levels within 10 and 11g% and its effects, if any, on the progression of chronic renal failure. Eighty-four pre-dialysis patients (46 F, 38M, age 61.7+13.9 years) with Hb levels between 6 and 9g% and serum creatinine ranging from 3 to 9 mg/dl were treated with s.c. rHu-EPO (2000 U/twice weekly). After 6 weeks, if Hb increase was below 1g%, 1000 U of s.c. rHu-EPO were added at each administration (3000 U twice weekly). Once the Hb target was reached (10–11g%), the rHu-EPO weekly dose was halved and administration reduced to once weekly. The patients showed a significant rise in mean Hb values (p&lt;0.001) after 3 months. Mean Hb values were as follows: 8.00±0.77g% (pretreatment), 9.35±1.0 (3rd month), 10.06±1.04 (6th month), 10.25±0.62g% (12th month). The mean rHu-EPO doses were 4000 U/w (start of the study), 3592+1685 U/w (6th month), 2840±1178 U/w (12th month). Renal function was evaluated by plotting the reciprocal of serum creatinine values vs time with a two period comparison: period A (retrospective-8 mo); period B (prospective-12 mo). The residual renal function was not impaired by rHu-EPO therapy. Meanwhile, no relevant modifications were observed in mean blood pressure values. Low doses of s.c. rHu-EPO were well tolerated, safe and effective; this therapeutic approach should therefore be considered for the improvement of anemia in pre-dialysis patients. A slow and gradual correction of anemia induces an improved sense of well being and a more active of life style. (Int J Artif Organs 1998; 21:12-8)

Serum transferrin receptor level as an index of the response to erythropoietin therapy for anemia in predialysis patients with chronic renal failure

Serum transferrin receptor level as an index of the response to erythropoietin therapy for anemia in predialysis patients with chronic renal failure

The use of recombinant human erythropoietin in predialysis patients

Recombinant human erythropoietin is increasingly used to treat anemia in predialysis patients. Approximately 33-40% of patients ultimately receiving dialysis or a transplant may be eligible for treatment, thus increasing the costs. Clinical trials demonstrate no significant alteration in the progression of renal disease, secondary to changes in systemic hemodynamics or blood volume, provided that blood pressure is controlled. Hypertension results from changes in viscosity and erythrocyte fluidity, loss of hypoxic vasodilatation, and changes in blood volume. The predialysis patient treated with recombinant human erythropoietin is likely to need aggressive antihypertensive therapy and vigorous diuresis. Cardiac output remains unchanged in the absence of blood volume expansion. The effects on left ventricular hypertrophy, left ventricular volume, or exercise-induced ischemic electrocardiographic changes in predialysis have not been studied systematically. Doses of recombinant human erythropoietin in predialysis patients tend to be lower when administered subcutaneously rather than intravenously, but the comparative cost-effectiveness of different dosing strategies is currently unknown. The dosing frequency can vary from three times a week to twice a month. The effect of anemia correction on the 'rehabilitation' of predialysis patients remains to be addressed.

Effects of Recombinant Human Erythropoietin on Renal Function in Chronic Renal Failure Predialysis Patients

A study was undertaken to ascertain the effects of recombinant human erythropoietin (r-HuEPO) on renal function in chronic renal failure predialysis patients. The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospectively in a large number of patients using reliable measures of glomerular filtration rate (GFR). To investigate the efficacy, safety, and impact of r-HuEPO therapy in chronic renal insufficiency patients, a 48-week, randomized, open-label, multicenter study was initiated in 83 anemic, predialysis (serum creatinine 3 to 8 mg/dL) patients. Serial GFRs were measured using 125I-iothalamate clearance. Forty patients were randomized to the untreated arm and 43 patients to the treatment arm (50 U/kg r-HuEPO subcutaneously three times weekly). Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups. During this 48-week study, GFR, mean arterial blood pressure, and daily protein intake were not significantly different between the two groups. There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function. This was demonstrated by the lack of a significant (P = 0.376) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated (-2.1 +/- 3.2 mL/min) and untreated (-2.8 +/- 3.5 mL/min) groups. This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease.

Subcutaneous recombinant human erythropoietin decreased anemia in predialysis patients with chronic renal failure

Source Citation Watson AJ, Gimenez LF, Cotton S, Walser M, Spivak JL. Treatment of the anemia of chronic renal failure with subcutaneous recombinant human erythropoietin. Am J Med. 1990;89:432-5. 2...

The Use of Recombinant Human Erythropoietin in the Correction of Anemia in Predialysis Patients and Its Effect on Renal Function: A Double-Blind, Placebo-Controlled Trial

Fourteen nondialyzed patients with chronic renal insufficiency (serum creatinine 265 to 972 mumol/L [3.0 to 11.0 mg/dL]) and severe anemia (hematocrit less than 30%) were randomized to receive either recombinant human erythropoietin (r-HuEPO) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38% to 40%. Anemia was significantly ameliorated in the treated patients. No acceleration in the progression of renal failure (1/serum creatinine v time) or change in serum potassium was noted for either the placebo or treated group over the 12-week period. Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation (plasma iron/total iron-binding capacity). This resulted in functional iron deficiency and the requirement for iron supplementation. The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study. Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group. This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period. Improved patient well-being as a result of the correction of anemia resulted in one patient refusing appropriate initiation of dialysis therapy.