Publications by authors named "Iain C Macdougall"

Anaemia in CKD-treatment standard.

Nephrol Dial Transplant

April 2024

Anaemia is one of the most common complications of chronic kidney disease (CKD), having a significant impact on quality of life, and is also associated with a number of adverse clinical outcomes. Its pathogenesis is multifactorial, caused largely by an inadequate production of erythropoietin from the diseased kidneys, with iron deficiency, inflammation, shortened red cell lifespan and enhanced blood loss also being contributory factors. The management of this condition was transformed in the late 1980s by the advent of recombinant human erythropoietin (epoetin), and treatment paradigms have developed over the last three decades, largely focusing on a combination of epoetin or its analogues (erythropoiesis-stimulating agents; ESAs) along with iron supplementation, often administered intravenously due to increased hepcidin levels limiting iron absorption from the gut.

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Background: In AFFIRM-AHF, treatment of iron deficiency with intravenous ferric carboxymaltose (FCM) reduced the risk of heart failure (HF) hospitalization and improved quality of life (QoL) vs placebo in patients stabilized following an acute HF (AHF) episode, with no effect on cardiovascular (CV) death. Diabetes and iron deficiency frequently accompany AHF. This post hoc analysis explored the effects of diabetes on outcomes in AFFIRM-AHF patients.

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Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency.

Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l).

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Background: Reduced kidney function is common among patients with heart failure. In patients with heart failure and/or kidney disease, iron deficiency is an independent predictor of adverse outcomes. In the AFFIRM-AHF trial, patients with acute heart failure with iron deficiency treated with intravenous ferric carboxymaltose demonstrated reduced risk of heart failure hospitalization, with improved quality of life.

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Background: Iron deficiency, with or without anemia, is an adverse prognostic factor in heart failure (HF). In AFFIRM-AHF (a randomized, double-blind placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalizations and mortality in iron-deficient subjects admitted for acute heart failure), intravenous ferric carboxymaltose (FCM), although having no significant effect on the primary end point, reduced the risk of HF hospitalization (hHF) and improved quality of life versus placebo in iron-deficient patients stabilized after an acute HF (AHF) episode. These prespecified AFFIRM-AHF subanalyses explored the association between hemoglobin levels and FCM treatment effects.

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Background: Impaired quality of life is common in patients with end-stage kidney disease. We report the baseline quality of life measures in participants from the PIVOTAL randomized controlled trial and the potential relationship with the primary outcome (all-cause mortality, myocardial infarction, stroke, and heart failure hospitalisation), and associations with key baseline characteristics.

Methods: This was a post hoc analysis of 2141 patients enrolled in the PIVOTAL trial.

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Article Synopsis
  • - The ASCEND-NHQ trial investigated the effectiveness of daprodustat in increasing hemoglobin levels and improving fatigue in adults with chronic kidney disease (CKD) stages 3-5, comparing it to a placebo over 28 weeks.
  • - Results showed that participants taking daprodustat experienced a significant mean change in hemoglobin (1.58 g/dl) compared to the placebo group (0.19 g/dl), with 77% of daprodustat users achieving a 1 g/dl increase.
  • - Additionally, the SF-36 Vitality score (which measures fatigue) improved more for those on daprodustat (7.3 points) than those on placebo (1.
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Article Synopsis
  • Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) affects 10-15% of chronic dialysis patients, and a study compared the investigational drug daprodustat with standard ESA treatment to understand the characteristics and predictors of this issue.
  • The study recruited 2,964 ESA-treated chronic dialysis patients and defined ESA hyporesponsiveness using specific criteria, finding that about 12% of participants were hyporesponsive.
  • Key predictors included geographic region (especially Latin America), lower body mass index, younger age, and certain blood levels, along with additional factors like female sex and a history of heart failure; notably, the geographic finding suggests a need for further research.
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Introduction: Anemia is common in chronic kidney disease (CKD) and is associated with increased cardiovascular risk and reduced quality of life, but is often sub-optimally managed. Most patients are managed in primary care alongside other comorbidities. Interventions to improve the management of anemia in CKD in this setting are needed.

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Background: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure.

Methods: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK.

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Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare and often fatal condition, frequently diagnosed in end-stage renal disease (ESRD) patients. Although exact pathogenesis remains unclear, iron supplementation is suggested as a potential risk factor. Iron and erythropoietin are the main stay of treatment for anaemia in ESRD patients.

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Introduction: Treatment of anemia in dialysis patients has been associated with increased risk of vascular access thrombosis (VAT). Proactive IV irOn Therapy in hemodiALysis Patients (PIVOTAL) was a clinical trial of proactive compared with reactive i.v.

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Objectives: For patients with a reduced left ventricular ejection fraction (LVEF) heart failure with reduced ejection fraction (HFrEF) and iron deficiency, administration of intravenous iron improves symptoms, exercise capacity and may in the following 12 months, reduce hospitalisations for heart failure. The Effectiveness of ntavenous ir treatent versus standard care in ptiets with heart failure and iron deficiency (IRONMAN) trial evaluated whether the benefits of intravenous iron persist in the longer term and impact on morbidity and mortality.

Methods: IRONMAN is a prospective, randomised, open-label, blinded endpoint (PROBE) event-driven trial.

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Background: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics.

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Article Synopsis
  • HIF prolyl hydroxylase inhibitors are emerging treatments for anemia linked to chronic kidney disease (CKD), with some already approved in Europe, China, and Japan but not yet in the U.S.
  • While these inhibitors effectively increase hemoglobin levels, there are significant safety concerns regarding their long-term use.
  • Ongoing research is exploring the broader applications of these drugs beyond anemia treatment in CKD.
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Aims: In AFFIRM-AHF, intravenous ferric carboxymaltose (FCM) reduced heart failure (HF) hospitalisations and improved quality of life versus placebo in iron-deficient patients stabilised after an acute HF episode. This analysis explored the effects of FCM versus placebo in patients with ischaemic and non-ischaemic HF aetiology.

Methods And Results: We included 1082 patients from AFFIRM-AHF: 590 with ischaemic HF (defined as investigator-reported ischaemic HF aetiology and/or prior acute myocardial infarction and/or prior coronary revascularisation) and 492 with non-ischaemic HF.

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Iron deficiency commonly affects patients with chronic kidney disease and has an important burden in disease trajectory and quality of life; nonetheless current guidelines do not advocate treatment of iron-deficiency without anemia in this patient group. Concerns exist regarding the potential effects of intravenous iron on oxidative stress, inflammation, and endothelial function. As part of a multicenter double-blinded randomized controlled clinical trial, we examined the effects of a single dose of intravenous iron vs.

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Article Synopsis
  • Daprodustat is being tested as an oral alternative to traditional ESAs for treating anemia in patients with chronic kidney disease starting dialysis, with limited past studies on this topic.
  • The clinical trial involved a randomized, open-label design across 90 centers in 14 countries, focusing on patients who were either set to begin dialysis soon or had started within the last 90 days.
  • The main goal was to compare the effectiveness and safety of daprodustat to darbepoetin alfa by assessing changes in hemoglobin levels and monitoring adverse events over a treatment period of 28 to 52 weeks.
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Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared with similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized, controlled trial of intravenous iron treatment strategies in HD.

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Aims: To investigate the effect of high-dose iron vs. low-dose intravenous (IV) iron on myocardial infarction (MI) in patients on maintenance haemodialysis.

Methods And Results: This was a pre-specified analysis of secondary endpoints of the Proactive IV Iron Therapy in Hemodialysis Patients trial (PIVOTAL) randomized, controlled clinical trial.

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Article Synopsis
  • Anaemia is a common issue for patients with chronic kidney disease (CKD), and it's crucial to evaluate new treatments like daprodustat compared to the existing drug, darbepoetin alfa.
  • The ASCEND-ND trial involved 3,872 adult participants across 39 countries, focusing on those with specific hemoglobin levels and assessing various health characteristics related to CKD.
  • The study aims to determine the effectiveness and safety of daprodustat in treating CKD-related anaemia in patients not on dialysis, providing important insights into managing this condition.
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The physiological role of iron extends well beyond hematopoiesis. Likewise, the pathophysiological effects of iron deficiency (ID) extend beyond anemia. Although inextricably interrelated, ID and anemia of chronic kidney disease (CKD) are distinct clinical entities.

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