Anaemia management in people with chronic kidney disease
This is an extract from the guidance. The complete guidance is available at guidance.nice.org.uk/cg114
This guideline updates and replaces NICE clinical guideline 39.
Internationally anaemia is defined as a state in which the quality and/or quantity of circulating red blood cells are below normal. Blood haemoglobin (Hb) concentration serves as the key indicator for anaemia because it can be measured directly, has an international standard, and is not influenced by differences in technology. However, because Hb values in healthy individuals within a population show a normal distribution, a certain number of healthy individuals will fall below a given cut-off point.
Why is anaemia important in patients with chronic kidney disease (CKD)? Possible adverse effects of anaemia include reduced oxygen utilisation, increased cardiac output and left ventricular hypertrophy, increased progression of CKD, reduced cognition and concentration, reduced libido and reduced immune responsiveness. How much these adverse effects translate into adverse outcomes such as impaired quality of life, increased hospitalisation, increased cardiovascular events and increased cardiovascular and all-cause mortality has been debated for several years. What is incontrovertible is that since the introduction of human recombinant erythropoietin for treating CKD-related anaemia over 2 decades ago we have had the tools to significantly influence anaemia management. The phenotype of the kidney patient with Hb levels between 5–8 g/dl, rendered massively iron over-loaded and virtually un-transplantable as a result of multiple transfusions, has thankfully become unrecognisable. Attention has shifted from treating severe anaemia in dialysis patients to preventing anaemia pre-dialysis and to correcting of anaemia to higher Hb levels.
It is well established that Hb levels fall as kidney function declines but there is significant heterogeneity at each level of kidney dysfunction. Although normal values for Hb in the general population differ by gender this has not been addressed in most study designs of anaemia in CKD. Observational data suggest that lower Hb values are associated with increased cardiovascular abnormalities/events, increased hospitalisation, increased mortality, increased transfusion requirements and reduced quality of life. Major criticisms levelled at observational studies have been their heterogeneity and the variation in adjustment for confounders. Randomised controlled clinical trials of correction of anaemia to higher versus lower levels of Hb have failed to demonstrate the expected improved outcomes, even suggesting potential harm. These too have been criticised, particularly on the basis that the treatment required to achieve Hb levels in the different studies has also been subject to confounding; these trials have served to highlight the potential importance of erythropoietin dose and individual responsiveness to anaemia treatment.
When 'Anaemia management in people with chronic kidney disease' (NICE clinical guideline 39) was published in 2006, guidance on limiting the upper level of Hb was primarily driven by health economics and a lack of evidence of additional benefit in people treated to levels of Hb greater than 12.5 g/dl. However, studies published after the guidance were consistent with a relative lack of benefit and possible harm in the process of aspiring to higher Hb levels, dictating a review of published recommendations.
New recommendations have been added for the diagnostic evaluation and assessment of anaemia and the assessment and optimisation of erythropoiesis.
Recommendations are marked as , [2006, amended 2011] or [new 2011].
 indicates that the evidence has not been updated and reviewed since 2006.
[2006, amended 2011] indicates recommendations where the evidence has not been reviewed since the original guideline but they have been amended because of GDG consensus that they no longer reflect clinical practice or to add clarity; or recommendations that need amending to be consistent with new recommendations.