Inflammation and its impact on anaemia in chronic kidney disease: from haemoglobin variability to hyporesponsiveness

Abstract

The availability of erythropoiesis-stimulating agents (ESAs) has revolutionized the treatment of anaemia in patients with chronic kidney disease. However, maintaining patients at haemoglobin (Hb) levels that are both safe and provide maximal benefit is a continuing challenge in the field. Based on emerging data on the potential risks of Hb treatment targets >13 g/dL, treatment targets have recently been lowered. In the latest revision (March 2008) of the European product labelling for the ESA class of drugs, the target treatment range was lowered to 10-12 g/dL. Fluctuation of Hb levels or 'Hb variability' during treatment with ESAs is a well-documented phenomenon. Hb levels that are either too high or too low may have an adverse effect on patient outcomes; thus, it is important to understand the causes of Hb variability in order to achieve optimal treatment. Several factors are believed to contribute to variation in the Hb level, including patient comorbidities and intercurrent events. Inflammation is also an important factor associated with Hb variability, and the consequences of persistent inflammatory activity are far-reaching in affected patients. This review addresses the complex role of inflammation in chronic kidney disease, as evidenced by the apparent state of deranged inflammatory markers. The mechanisms by which inflammatory cytokines may affect the response to ESAs, the development of anaemia and poor treatment outcomes are also examined. In addition, various options for intervention to enhance the response to ESAs in haemodialysis patients with inflammation are considered.

Fig. 1

Factors associated with Hb variability. Hb, haemoglobin; sHPT, secondary hyperparathyroidism; PRCA, pure red cell aplasia; RBC, red blood cell.

Fig. 2

Hb levels and risk for mortality and hospitalization in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Hb, haemoglobin. Reprinted from [10], Copyright (2004), with permission from Elsevier.

Fig. 3

Relationship between inflammatory cytokines and response to epoetin. IL, interleukin; rh-EPO, recombinant human erythropoietin; TNF-α, tumour necrosis factor-α. Reprinted from [40] by permission from Macmillan Publishers Ltd.

Fig. 4

Correlation between change in TNF-α and Hb in patients treated with pentoxifylline [74]. Hb, haemoglobin; TNF-α, tumour necrosis factor-α.