Anemia in Chronic Kidney Disease Clinical Trials: A Critical Appraisal

Abstract

The pivotal role of haemoglobin as one of the targets in the holistic management of dialysis patients was the focus of the first published anaemia guidelines by KDOQI in 1997. Since the introduction of erythropoietin to anaemia management in chronic kidney disease, there has been a continuous debate on the optimal haemoglobin target required to achieve the desirable clinical outcome whether in survival or quality of life. With the unequivocal evidence of the impact of these agents on relatively better quality of life and reduced need for red-cell transfusion with the anticipated potential complications attached to it, there is an element of uncertainty about the exact risk of these agents on chronic kidney disease patients. Iron deficiency is the other area that attracts a lot of interest in anaemia management in chronic kidney disease. Absolute and relative iron deficiencies are recognised for a long time as important contributing factors for anaemia development in different stages of chronic kidney disease. More importantly, response to erythropoiesis stimulating agents (ESAs) is suboptimal in the presence of iron deficiency. Most of the up-to-date anaemia guidelines emphasise on the central role of iron in anaemia management. Disappointing enough, iron treatment recommendations are either not graded or scored low. This emphasises the unmet need for better quality evidence to address a confusing dilemma in iron treatment in this group of patients. Disproportionately, a large number of high-quality and well-designed studies became available in ESA treatment area which allowed for high-rank quality of evidence. Questions that remain without clear answers are: When to start iron treatment? Which route of administration to use? What are the targets of iron treatment? What are the best biochemical variables that reflect iron status? A very limited number of reasonable quality studies have tried to answer some of these questions. I included some of those trials that attracted a lot of debate in this area and have remarkable impact on anaemia management in chronic kidney disease patients whether on dialysis or not. I also randomly included some of the landmark ESA trials at different levels of chronic kidney disease.