Special issue: iron therapy in patients with chronic kidney disease

Iron deficiency is the most common micronutrient deficiency in the world, affecting approximately one-quarter of the world’s population [1]. It is also very common among patients with chronic kidney disease (CKD), affecting a majority of patients [2–5]. Iron deficiency in CKD arises from a combination of poor dietary iron intake, impaired absorption of iron by the gut, and greater iron losses, particularly among CKD patients treated with haemodialysis. Iron is a key component of haemoglobin in red blood cells, and plays numerous other roles throughout the body. Iron deficiency can therefore have widespread physiological consequences, whether or not overt anaemia is present. Symptoms of iron deficiency and anaemia include fatigue, cognitive impairment, and restless legs. In patients with CKD, iron deficiency and anaemia are associated with lower quality of life and worse outcomes [6], motivating the use of iron therapy in an attempt to mitigate the deficiency. Iron therapy is currently delivered in one of two forms: oral or intravenous (IV). For patients with CKD not being treated with haemodialysis, oral iron may be considered, although the high pill burden and gastrointestinal side effects may limit patient adherence. In haemodialysis patients, IV iron infusion is the current therapy of choice. In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published new guidelines for the use of iron therapy in patients with CKD [7]. Although IV iron therapy is now common, there continues to be uncertainty and controversy regarding its use. This ongoing dialogue was highlighted by a recent KDIGO Controversies Conference [8], as well as the subsequent publication of two clinical trials (FIND-CKD [9] and REVOKE [10]) that reached opposing conclusions regarding the safety of IV iron. In this Supplement, we attempt to summarize current knowledge regarding the use of iron therapy in patients with CKD, while highlighting areas of ongoing debate and research. First, Jeffrey Berns provides an in-depth discussion of the KDIGO guidelines for the use of iron therapy in patients with CKD, focusing on those areas that have provoked debate and discussion among clinicians in the field. Next, Simon Roger highlights the practical considerations for implementing the KDIGO guideline recommendations for the use of iron therapy in the management of anaemia in patients with CKD, and discusses key treatment decisions facing the nephrologist. The third article, by Iain Macdougall, discusses the implications of randomized clinical trials (notably FIND-CKD [9] and REVOKE [10]) and observational analyses published subsequent to the KDIGO guidelines that further discuss the use of iron in patients with CKD. Finally, Jolanta Malyszko and Stefan Anker summarize recent evidence on the use of iron therapy to treat iron deficiency (as opposed to overt anaemia), particularly in patients with heart failure, and discuss possible implications for the treatment of patients with CKD.