Cordelia Ashwanden PhD RN,
Editor

Foreword
Jane Macdonald MPhil, BSc (Hons), RN
Renal Services, Salford Royal NHS Foundation Trust, Salford, UK

Evolution of IV iron compounds over the last century
Iain C Macdougall, BSc, MD, FRCP
Consultant Nephrologist and Honorary Senior Lecturer
Department of Renal Medicine, King’s College Hospital, London, UK

CORRESPONDENCE
Dr Iain C Macdougall
Consultant Nephrologist
Renal Unit
King’s College Hospital
London SE5 9RS
Tel No: ++44-203-299-6236
Fax No: ++44-203-299-6472
e-mail: Iain.macdougall@kch.nhs.uk

SUMMARY
Administration of intravenous iron has become pivotal in the management of anaemia in patients with chronic kidney disease (CKD).  Since parenteral iron was first introduced for human use in the 1930s, things have come a long way. 70 years ago, iron was toxic, administered as an iron oxyhydroxide complex.  This problem was circumvented with the introduction of compounds containing iron in a core surrounded by a carbohydrate shell.  The carbohydrate shell consists of molecules such as dextran, sucrose, dextrin, or gluconate.  The first dextran-containing IV iron preparations carried a small risk of anaphylaxis, but the more recently-introduced low molecular weight iron dextran preparation has significantly less risk of this.  Iron reactions occur with all IV iron preparations, but are generally not thought to be immune-based.  Recently, newer IV iron preparations have appeared in the market, including Feromoxytol (Feraheme^®) and ferric carboxymaltose (Ferinject^®).  These latest IV iron preparations do not contain a requirement for a test dose, and a much higher dose of iron can be delivered as a single administration.  Thus, giving supplemental iron to man has come a long way since the 1930s, we are now in an era when we are able to administer higher doses of iron with acceptable safety and without significant adverse effects.  However, the long-term safety of the newer IV iron preparations is not yet established.

KEY WORDS
Anaemia, Iron deficiency, CKD, Haemoglobin

Csaba P Kovesdy^1,2 and Kamyar Kalantar-Zadeh^3,4

¹ Division of Nephrology, Salem Veterans Affairs Medical Center, Salem, VA;
²Department of Medicine, University of Virginia, Charlottesville, VA;
³Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502;
⁴David Geffen School of Medicine at UCLA, Los Angeles, CA 90023

CORRESPONDENCE
Csaba P Kovesdy, MD, FASN
Division of Nephrology, Salem VA Medical Center
1970 Roanoke Blvd., Salem, VA 24153
Phone: 540-982 2463 Fax: 540-224 1963
E-mail: csaba.kovesdy@va.gov

SUMMARY
Anaemia in chronic kidney disease (CKD) is a complex disease which requires an integrated approach to incorporate both diagnostic and therapeutic interventions and to address the different facets of its aetiology and pathophysiology. The advent of erythropoiesis stimulating agents (ESA) has revolutionised the therapy of anaemia of CKD, and has resulted in a significant decline in the need for blood transfusions in CKD patients. The routine application of ESA has also led to the need for concomitant iron supplementation. ESA and iron therapy now form the cornerstone of anaemia management in CKD. Intravenous iron administration is effective with acceptable safety, and may improve ESA responsiveness. However, less is known about the long term safety of iron supplementation in CKD patients. Whereas maintenance (weekly to monthly) intravenous iron has been routinely used in maintenance dialysis patients, iron replacement in patients with non-dialysis dependent CKD is less well studied, in spite of the much larger number of patients affected. This review discusses iron supplementation in CKD with an emphasis toward controversial issues that continue to pose dilemmas in clinical practice. Concerns related to both the optimal amount of iron supplementation and to the safety of various agents available in clinical practice are presented.

KEY WORDS
Anaemia, Chronic Kidney Disease, Erythropoiesis-Stimulating Agents, Haemoglobin

T.J. Littlewood MD FRCP FRCPath.

CORRESPONDENCE
Dr T Littlewood
Consultant Haemotologist
Department of Haematology,
Cancer and Haematology Centre,
Churchill Hospital,
Old Rd,
Oxford
OX3 7LJ
e-mail; tim.littlewood@chch.ox.ac.uk
Telephone. 00 44 (0) 1865 235882

SUMMARY
Symptomatic anaemia is found in patients with chronic kidney disease. Correction of anaemia by Erythropoiesis Stimulating Agents improves quality of life and life expectancy. Data in patients with both dialysis dependent and non-dialysis dependent chronic kidney disease now show that the mortality from cardiovascular disease increases if the haemoglobin concentration is corrected above 13.0g/dl. The mechanism for this increased risk is uncertain.

KEY WORDS
Anaemia, Chronic Kidney Disease, Haemoglobin

Donal J O’Donoghue MBChB, MRCP, FRCP

CORRESPONDENCE
Dr Donal O’Donoghue
Department of Renal Medicine,
Salford Royal Hospitals NHS Foundation Trust,
Hope Hospital,
Stott Lane,
Salford M6 8HD, UK
Email: Donal.o’donoghue@srft.nhs.uk

SUMMARY
Chronic kidney disease (CKD) is common, harmful and treatable but has until recently not been recognised in its early stages.  The British National Health Service provides a unique opportunity to study CKD because it is in effect a closed managed care system.  This single healthcare system for the United Kingdom is funded by the Government and paid for by general taxation.  All United Kingdom citizens are registered with primary care physicians who control access to secondary care services.  As a managed care system it should be able to offer integrated care across the whole patient pathway - allowing early identification of CKD, interventions to reduce risk and prompt management of complications.  In reality there are professional, organisational and institutional barriers to co-ordination and delivery of care in the NHS. 
The establishment of general practice based disease registers linked to a quality and outcomes framework in 2004 provides a basis for implementing the chronic disease model of care.  The publication of the National Service Framework for renal services complemented by these changes in primary care has resulted in a paradigm shift from kidney disease being viewed as a secondary care condition to being a primary care priority as part of vascular control and management. 
In the first two years of the initiative, over 40% of the expected CKD stage 3 to 5 population have been registered in primary care.  Kidney disease is now recognised as a public health problem in the United Kingdom, preventative strategies are being integrated into comprehensive vascular risk assessments and management programmes and kidney disease has become an NHS priority area.

KEY WORDS
Chronic Kidney Disease, National Service framework, primary care, National Kidney Foundation

Karen Jenkins RN, MSc, PG Dip HE

CORRESPONDENCE
Karen Jenkins RN, MSc, PG Dip HE
Consultant Nurse Kent Kidney Care Centre +Renal Admin Block
East Kent Hospitals University NHS Foundation Trust
Kent & Canterbury Hospital
Ethelbert Road
Canterbury
Kent CT1 3NG
Karen.jenkins@ekht.nhs.uk
Tel: 01227864142 – work

SUMMARY
The use of intravenous iron is now part of the every day management of anaemia in people with Chronic Kidney Disease (CKD). The increase in the number of referrals to renal services since the introduction of estimated glomerular filtration rate (eGFR) reporting in 2006 in England, means that people with CKD are being identified earlier and consequently, complications such as anaemia are being highlighted sooner. The prevalence of anaemia of CKD has been estimated in a population study of stage 3-5 CKD as 4.5% (John et al 2004). People with stage 3 CKD and diabetes have a 22% incidence of anaemia which is much greater than the incidence of 7.9% in those without diabetes (El Achkar et al 2005). The increase in numbers requiring anaemia management is having an impact on resources and service provision, in particular the treatment of iron deficiency with intravenous iron. A need to be creative and investigate alternative ways of using resources and providing services in different settings was identified by the multi-professional members of the Anaemia Nurse Specialist Association (ANSA) and the CKD forum (a project group of the British Renal Society). The outcome has been the production of a practical guide for healthcare professionals to assist with the development of intravenous iron services in a non acute hospital setting. The guide was launched at the annual ANSA conference (April 2009) and British Renal Society conference (June 2009).

KEY WORDS
Anaemia, Chronic Kidney Disease, intravenous iron, competencies, Patient centred care

Karen Pugh–Clarke  MSc. BSc(Hons). RN
Anaemia Management Sister and Renal Research Nurse, University Hospital of North Staffordshire.

CORRESPONDENCE
North Staffordshire Hospital
Renal Unit – Wd 30
Princes Road,
Hartshill
ST4 7LN Stoke-On-Trent
United Kingdom
Tel.            ++44-1782715444
Fax.           ++44-1782716615
Email          Karen.Pugh-Clarke@uhns.nhs.uk

SUMMARY
The use of Evidence-based practice (EBP) is a decision making process, which integrates the best available research, clinician expertise, and client characteristics, integrating quality patient care in terms of clinical outcomes and cost-effectiveness. This paper describes the application of EBP to an outpatient intravenous (IV) iron clinic for patients with pre-dialysis chronic kidney disease (CKD).
There has been an increasing focus on managing anaemia in patients with pre-dialysis CKD. Along with the use of erythropoiesis stimulating agents (ESAs), there has been an emerging interest in the use of IV iron preparations to treat anaemia in this patient population.
Using EBP we introduced a single dose preparation Ferinject^® to replace our original IV iron protocol using Venofer^®;. As a test dose of Ferinject^® is not required, it is extremely appropriate for use in busy nurse-led IV iron clinics.
Based upon the evidence generated from our initial trial of using Ferinject^®, and our clinical experience of using this preparation, we have now converted our IV iron protocol to Ferinject^®. Although the evaluation of Ferinject^® in our pre-dialysis population is ongoing, we are continuing to observe the benefits of using this preparation, both in terms of patient outcome and cost effectiveness.  We consider that the use of Ferinject^® has reduced waiting time and waiting list pressure, and also reduced material and hospital transport costs, which are significant due to the large geographical area covered by our CKD service.

KEY WORDS
Evidence-based practice, Chronic kidney disease, Anaemia, Ferinject^®, Nurse-led clinic