Abstract
Erythropoiesis-stimulating agents (ESAs) and iron therapy are the standard of care for normocytic normochromic anaemia, which is a frequent comorbidity of patients with chronic kidney disease. In a large percentage of patients, ESAs and iron increase haemoglobin levels, thus reducing the risk of blood transfusions and improving patient quality of life. However, randomised trials have raised some concerns about higher haemoglobin targets and/or high ESA dose use. These concerns include higher cardiovascular and thrombosis risk, cancer progression, and increased mortality. A more cautious approach was then advised and partial anaemia correction (haemoglobin 10-12 g/dl) is now strongly suggested. The clinical concerns about ESAs and economic constraints have led to larger intravenous iron use. However, severe anaphylactic reactions, although infrequent, can occur and excessive iron use may be dangerous as well, possibly causing iron overload. Several attempts are being made to develop new drugs with theoretically better activity and safety, and/or easier manufacturing processes as compared to available ESAs. These include drugs manipulating the hypoxia-inducible transcription factor (HIF) system, which stimulates the endogenous erythropoietin (EPO) production and avoids unphysiological EPO plasma levels. Several phase I and II studies support the beneficial role of augmenting HIFs to stimulate erythropoiesis. Here we give an update on this new investigational strategy.
Published Version
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