Title: Daprodustat for treating anaemia in adults with chronic kidney disease [ID3987]
Funder: Department of Health and Social Care

Abstract: Anaemia in chronic kidney disease (CKD) contributes significantly to the burden of CKD. It is defined as a state in which the quality or quantity of circulating red blood cells is below normal. A major cause of anaemia in CKD is a reduction in erythropoietin production because of kidney damage. Erythropoietin stimulates the bone marrow to produce red blood cells (erythropoiesis), and it is made by the kidney in response to low tissue oxygen levels. Other factors that can contribute to development of anaemia in CKD include blood loss (for example, from haemodialysis), a reduced ability to absorb and use iron to make new red blood cells, and inflammation and infection which can suppress the bone marrow[1] . Adverse effects of anaemia include reduced oxygen use, fatigue, increased cardiac output, left ventricular hypertrophy, reduced cognition and concentration, reduced libido and reduced immune responsiveness [1] . _x000D_ _x000D_ Blood haemoglobin concentration is a key indicator for anaemia because it can be measured directly and has an international standard. NICE guideline 203 (NG203) recommends that clinicians consider investigating and managing anaemia in CKD if a patient’s haemoglobin level falls to 110 g/litre or less (or 105 g/litre or less if the patient is younger than 2) or they develop symptoms of anaemia such as tiredness, shortness of breath, lethargy and palpitations. _x000D_ _x000D_ CKD is divided into 5 stages defined by evidence of kidney damage, level of renal function as measured by glomerular filtration rate (GFR), and degree of albuminuria. The prevalence of anaemia increases progressively with each CKD stage. The Health Survey for England (2016) found that 13% of adults (16 years and over) had CKD (stages 1 to 5). The prevalence of stage 3 to 5 CKD was 5% for all adults, rising to 34% in people aged 75 and over[2] . A cross-sectional study based on data from the Quality Improvement in Chronic Kidney Disease trial, which was conducted in 127 practices from localities across England (2013), reported that the prevalence of anaemia in people with CKD stage 3–5 is 8.6%[2],[3] . _x000D_ _x000D_ Anaemia associated with CKD is potentially reversible with appropriate treatment such as erythropoiesis-stimulating agents (ESAs), iron therapy, or both, depending on the cause of the anaemia. NG203 recommends ESA therapy, for people who are likely to benefit in terms of quality of life and physical function. NG203 does not recommend any specific ESAs, but states that the choice of treatment should take into consideration the patient's dialysis status, the route of administration and local availability of ESAs. ESA therapy should not be initiated in the presence of absolute iron deficiency without also managing the iron deficiency. In addition, iron therapy should be offered to people who are iron deficient and who are not on ESA therapy. Blood transfusions may be clinically indicated in some situations but are avoided where possible in people with anaemia of CKD in whom a kidney transplant is a treatment option._x000D_ _x000D_ References_x000D_ 1 Kidney Research UK Anaemia and kidney disease. Accessed June 2020._x000D_ 2 Health survey for England, 2016. Accessed June 2020_x000D_ 3 Dmitrieva O, de Lusignan S, Macdougall IC, et al. Association of anaemia in primary care patients with chronic kidney disease: cross sectional study of quality improvement in chronic kidney disease (QICKD) trial data. BMC Nephrol. 2013;14:24. Published 2013 Jan 25. doi:10.1186/1471-2369-14-24

Lay abstract: To appraise the clinical and cost effectiveness of daprodustat within its marketing authorisation for treating anaemia in adults with chronic kidney disease.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RENAL AND UROGENITAL