Nutrition, anaemia and erythropoietin therapy

This article has no abstract

Recombinant Human Erythropoietin in the Treatment of Renal Anaemia

This thesis is concerned with a study of the clinical and biological effects of recombinant human erythropoietin (EPO) which recently became available as a novel treatment for the anaemia of end-stage renal disease. The dissertation begins with an introductory chapter which contains a historical note and survey of the relevant published literature. In this section is included a review of the pathogenesis of renal anaemia, the traditional treatment options for this condition, the development of recombinant human EPO, the biochemistry and physiology of erythropoietin, the metabolic fate of EPO, and the early clinical trials with EPO. This is followed by seven chapters of original work undertaken in Cardiff between April 1988 and July 1990

PRE‐dialysis survey on anaemia management

Background. The PRE‐dialysis survey on anaemia management (PRESAM) was designed to assess the care given to pre‐dialysis patients in the 12 months before haemodialysis or peritoneal dialysis, with emphasis on anaemia management. Methods. For this epidemiological study, a retrospective chart review was conducted for patients who started haemodialysis or peritoneal dialysis between 1 August, 1999 and 6 April, 2000. All adult patients who entered one of the 779 participating centres in 21 European countries, Israel or South Africa were included, except for patients who underwent dialysis only during an acute episode. In addition to demographic characteristics, the study examined the prevalence of anaemia, anaemia management including the use of iron supplementation and epoetin, source of referral to the dialysis centre, comorbidities and major clinical events. Results. A total of 4333 new dialysis patients were included in the survey. At the first visit to the dialysis centre, 68% of the patients had a haemoglobin (Hb) concentration ≤11.0 g/dl; Hb concentration was positively correlated with creatinine clearance rate (r=0.43, P<0.01). Patients who received epoetin had a mean Hb concentration of 8.8 g/dl at the start of epoetin treatment, and 96% of these patients had an Hb concentration ≤11.0 g/dl. Only 26.5% of the patients received epoetin before dialysis. The length of time under the care of a nephrologist was associated with meeting the European Best Practice Guidelines (EBPG) target Hb concentration, as well as receiving epoetin. Conclusions. Few pre‐dialysis patients met the EBPG target for Hb concentration, despite regular nephrology car

Association of anaemia in primary care patients with chronic kidney disease: cross sectional study of quality improvement in chronic kidney disease (QICKD) trial data

Background: Anaemia is a known risk factor for cardiovascular disease and treating anaemia in chronic kidney disease (CKD) may improve outcomes. However, little is known about the scope to improve primary care management of anaemia in CKD. Methods: An observational study (N = 1,099,292) with a nationally representative sample using anonymised routine primary care data from 127 Quality Improvement in CKD trial practices (ISRCTN5631023731). We explored variables associated with anaemia in CKD: eGFR, haemoglobin (Hb), mean corpuscular volume (MCV), iron status, cardiovascular comorbidities, and use of therapy which associated with gastrointestinal bleeding, oral iron and deprivation score. We developed a linear regression model to identify variables amenable to improved primary care management. Results: The prevalence of Stage 3–5 CKD was 6.76%. Hb was lower in CKD (13.2 g/dl) than without (13.7 g/dl). 22.2% of people with CKD had World Health Organization defined anaemia; 8.6% had Hb ≤ 11 g/dl; 3% Hb ≤ 10 g/dl; and 1% Hb ≤ 9 g/dl. Normocytic anaemia was present in 80.5% with Hb ≤ 11; 72.7% with Hb ≤ 10 g/dl; and 67.6% with Hb ≤ 9 g/dl; microcytic anaemia in 13.4% with Hb ≤ 11 g/dl; 20.8% with Hb ≤ 10 g/dl; and 24.9% where Hb ≤ 9 g/dl. 82.7% of people with microcytic and 58.8% with normocytic anaemia (Hb ≤ 11 g/dl) had a low ferritin (<100ug/mL). Hypertension (67.2% vs. 54%) and diabetes (30.7% vs. 15.4%) were more prevalent in CKD and anaemia; 61% had been prescribed aspirin; 73% non-steroidal anti-inflammatory drugs (NSAIDs); 14.1% warfarin 12.4% clopidogrel; and 53.1% aspirin and NSAID. 56.3% of people with CKD and anaemia had been prescribed oral iron. The main limitations of the study are that routine data are inevitably incomplete and definitions of anaemia have not been standardised. Conclusions: Medication review is needed in people with CKD and anaemia prior to considering erythropoietin or parenteral iron. Iron stores may be depleted in over >60% of people with normocytic anaemia. Prescribing oral iron has not corrected anaemia

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

Intravenous Iron and Maintenance Hemodialysis

No abstract available

New options for the anemia of chronic kidney disease:Changing the Paradigms for the Treatment of Chronic Kidney Disease

Anemia is a common complication of chronic kidney disease. Use of erythropoiesis-stimulating agents (ESA) has been a mainstay of treatment since 1990. A series of large trials demonstrated that ESAs have serious safety problems, including increasing cardiovascular and thrombotic events, and death. Analyses suggest high pharmacologic doses of ESAs, rather than the highly achieved hemoglobin, may mediate harm. Hypoxia-inducible factor (HIF) activators stimulate endogenous erythropoietin production and enhance iron availability. In early clinical trials, these oral agents appear to be capable of replacing ESA therapy and minimizing the need for i.v. iron therapy for chronic kidney disease–related anemia, while having other potentially advantageous actions. Large phase 3 trials are underway with several HIF activators. This commentary reviews trends in anemia management, the safety issues related to our present therapies, the role of HIF in regulating erythropoiesis, and the diverse actions of HIF activators

Measuring fatigue in haemodialysis patients: The factor structure of the Chalder Fatigue Questionnaire (CFQ)

Introduction Fatigue is common in haemodialysis (HD) patients, leading to poorer quality of life and patient outcomes. Given the complex and subjective nature of fatigue, and its overlap with sleep disturbances and depression, its measurement represents a challenge. Our aim was to evaluate the psychometric properties of the 11-item Chalder Fatigue Questionnaire (CFQ) in HD patients, including an assessment of the validity of the factor structure, internal reliability and discriminant validity with respect to functional impairment due to fatigue, psychological distress and comorbidity. Methods Data were evaluated for psychometric analysis from a published study investigating clinical and psychosocial correlates of fatigue among 174 HD patients. Confirmatory factor analysis was used to determine the factor structure using Weighted Least-Squares with Mean and Variance (WLSMV) adjustment estimation. Mplus 7.3 was used for the analysis. Results Mental and physical fatigue factors correlated highly (r = .70, p &lt; .01). A bi-factor model with one general fatigue factor, which incorporated three smaller group factors (mental, physical and weakness) had good model fit. The CFQ general factor explained over 85% of the common variance, had high internal consistency, and showed a moderate correlation with distress and a small association with comorbidity and functional impairment. Conclusions The CFQ can be summed up to a total fatigue severity score, representing a composite factor of physical and mental symptoms. Taking into consideration the good psychometric properties of the CFQ and its brief length, it should be used in future studies interested in measuring fatigue severity in HD patients