Excerpt

Anaemia is defined internationally as a state in which the quality and/or quantity of circulating red blood cells is below normal. Blood haemoglobin (Hb) concentration serves as the key indicator for anaemia because it can be measured directly and has an international standard. In response to low tissue oxygen levels in anaemia the kidney produces the hormone erythropoietin which stimulates the bone marrow to produce red blood cells. A major cause of the anaemia of chronic kidney disease (CKD) is a reduction in erythropoietin production due to kidney damage.

Why is anaemia important in patients with chronic kidney disease? Possible adverse effects of anaemia include reduced oxygen utilisation, increased cardiac output and left ventricular hypertrophy, reduced cognition and concentration, reduced libido and reduced immune responsiveness.

This guideline covers the management of anaemia in adults, children and young people with a clinical diagnosis of anaemia associated with CKD. It does not cover people with anaemia not principally caused by CKD. All parts of the care pathway are covered in the guideline. The guideline development group for this 2015 update considered the evidence in several areas that provide challenges for clinicians managing the anaemia of CKD. Recombinant human erythropoietin (also called ‘EPO’, or an erythropoietic stimulating agent or ESA) for treating anaemia of CKD provides a key tool in managing the anaemia of CKD. Some CKD patients with anaemia who are receiving an ESA are ‘ESA resistant’ – that is, their condition consistently fails to respond to the effects of the ESA. Patients with such a condition often receive large doses of ESA with or without blood transfusions, with limited benefits and at significant cost to healthcare. Many CKD patients receiving an ESA are admitted with an intercurrent illness – such as pneumonia – which may temporarily render them acutely hyporesponsive to that ESA. There is uncertainty about the management of these groups of patients, and these areas were considered in the update. The often limited trial evidence in nephrology, compared to other specialities, was again highlighted.

Over the past decade or more, attention has shifted to the role and management of iron deficiency in anaemia of CKD. In CKD patients there is often a complex inflammatory state which renders the diagnosis of iron deficiency difficult when using its standard markers, such as serum iron, serum total iron binding capacity or ferritin. In recent years evidence has been published on newer markers of iron deficiency and intravenous iron preparations. In this 2015 update, the guideline development group reassessed the diagnosis and management of iron deficiency in CKD, and made several recommendations in these areas.

Contents

• Foreword
• Partial Update 2015
• Guideline development group members [2006]
• Guideline development group members [2011]
• Guideline development group members [2015]
• 1. Introduction [2015]
  • 1.1. Definition of anaemia
  • 1.2. Chronic kidney disease: definition and prevalence
  • 1.3. How to use this guideline
  • 1.4. Recommendations for children with anaemia of CKD
• 2. Methodology [2006]
  • 2.1. Aim
  • 2.2. Scope
  • 2.3. Audience
  • 2.4. Involvement of people with anaemia of CKD
  • 2.5. Guideline limitations
  • 2.6. Other work relevant to the guideline
  • 2.7. Background
  • 2.8. The process of guideline development
  • 2.9. Disclaimer
  • 2.10. Funding
  • Methodology [2011]
  • 2.11. Developing the review questions and outcomes
  • 2.12. Searching for evidence
  • 2.13. Evidence of effectiveness
  • 2.14. Appraising the quality of evidence by outcomes
  • 2.15. Evidence of cost-effectiveness [2011]
  • Methodology [2015]
  • 2.16. Developing the review questions and outcomes
  • 2.17. Searching for evidence
  • 2.18. Evidence of effectiveness
  • 2.19. Evidence of cost-effectiveness
  • 2.20. Developing recommendations
• 3. Key messages of the guideline
  • 3.1. Key priorities for implementation
  • 3.2. Complete list of recommendations
  • 3.3. Algorithm [2011]
  • 3.4. Algorithm [2015]
  • 3.5. Audit criteria [2006, updated 2011]
• 4. Diagnostic evaluation and assessment of anaemia
  • 4.1. Diagnostic role of Hb levels [2006]
  • 4.2. Diagnostic role of glomerular filtration rate [2006]
  • 4.3. Diagnostic tests for the prediction of response to iron therapy [2015]
  • 4.4. Measurement of erythropoietin [2006]
• 5. Management of anaemia
  • 5.1. Initiation of ESA therapy in iron-deficient patients [2006]
  • 5.2. Maximum iron levels in patients with anaemia of CKD [2006]
  • 5.3. Clinical utility of ESA therapy in iron-replete patients [2006]
  • 5.4. Nutritional supplements [2006]
  • 5.5. Androgens [2006]
  • 5.6. Hyperparathyroidism [2006]
  • 5.7. Patient-centred care: ESAs [2006]
  • 5.8. Patient education programmes [2006]
• 6. Assessment and optimisation of erythropoiesis
  • 6.1. Benefits of treatment with ESAs [2006]
  • 6.2. Blood transfusions [2006]
  • 6.3. Comparison of ESAs [2006]
  • 6.4. Early or deferred ESA therapy [2006]
  • 6.5. Coordinating care [2006]
  • 6.6. Providing ESAs [2006]
  • 6.7. ESAs: optimal route of administration [2006]
  • 6.8. ESAs: dose and frequency [2006]
  • 6.9. Optimal Hb levels [2006]
  • Clinical methodological introduction [2011]
  • Evidence Profiles [2011]
  • Clinical evidence statements [2011]
  • 6.10. Optimum haemoglobin levels in children with anaemia of CKD [2006]
  • Optimum haemoglobin levels in children with anaemia of CKD [2011]
  • 6.11. Adjusting ESA therapy [2006]
  • 6.12. Concurrent illness [2015]
  • 6.13. Treating iron deficiency: correction [2006, 2015]
  • 6.14. Treating iron deficiency: maintenance [2006, 2015]
  • 6.15. Iron therapies [2015]
  • 6.16. ESAs: monitoring iron status during treatment [2006]
• 7. Monitoring treatment of anaemia of CKD
  • 7.1. Monitoring iron status [2006, 2015]
  • 7.2. Monitoring haemoglobin levels [2006]
  • 7.3. Detecting ESA resistance [2006]
  • 7.4. Managing ESA resistance [2006]
  • 7.5. Treatment of ESA resistance [2015]
• 8. Glossary
• 9. Reference list
• Appendices
  • Appendix A. Scope
  • Appendix B. Declarations of interest
  • Appendix C. Clinical review protocols
  • Appendix D. Economic review protocol
  • Appendix E. Clinical article selection
  • Appendix F. Economic article selection
  • Appendix G. Literature search strategies
  • Appendix H. Clinical evidence tables
  • Appendix I. Economic evidence tables
  • Appendix J. QUADAS-2 criteria
  • Appendix K. GRADE tables
  • Appendix L. Forest plots
  • Appendix M. Excluded clinical studies
  • Appendix N. Excluded economic studies
  • Appendix O. Cost-effectiveness analysis for the 2015 update: Diagnostic tests for predicting response to iron therapy
  • Appendix P. Diagnostic meta-analysis
  • Appendix Q. Research recommendations
  • Appendix R. Changes to recommendations from 2011 guideline
  • Appendix S. NICE technical team
  • Appendix T. References

This is a partial update of the 2011 clinical guideline on Anaemia Management in Chronic Kidney Disease. The sections new or updated in 2015 are: Guideline development group and scope; Methodology; Diagnostic tests for the prediction of response to iron therapy; Concurrent illness; Iron therapies; Treatment of ESA resistance. All other sections and recommendations from the 2011 guideline remain unchanged. The content of other sections has not been amended and we have integrated these new sections into the relevant chapters of the old publication. This has inevitably led to inconsistencies in style of write up for reviews.