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New developments in anaemia treatment - erythropoietin versus prolyl hydroxylase inhibitors?

Publication at First Faculty of Medicine |
2022

Abstract

Anaemia is a very common complication of chronic kidney disease (CKD) and renal failure. The view of the treatment of anaemia has changed considerably since the introduction of ESAs (erythropoiesis-stimulating agents) into clinical practice, and the safety of this treatment is now prioritised over complete normalisation of haemoglobin (Hb) values.

Iron administration is the mainstay of treatment in this group of patients, with intravenous administration proving to be both more effective and safer in both predialysis and dialysis patients. In addition to the long-used ESAs, a number of new agents developed to favourably influence erythropoiesis have recently been tested for the correction of anaemia.

Among those with the greatest potential are the HIF-stabilizers (roxadustat, molidustat, vadadustat and daprodustat), which act through stimulation of erythropoiesis genes and thus represent a novel mechanism of action in the treatment of anaemia. In phase 3 clinical trials, these agents have shown the same efficacy in increasing Hb levels as ESAs, but much emphasis has recently been placed on their safety profile.

They are orally administered agents and some of them are already approved and used in clinical practice. The first of these, roxadustat, is currently reimbursed also in the Czech Republic.

Other molecules affecting anaemia, such as sotatercept, have also been confirmed to be effective in phase 1 and 2 clinical trials and are awaiting results from larger randomised trials.