Prolyl hydroxylase domain-2 (PHD2) inhibition may be a better therapeutic strategy in renal anemia

Med Hypotheses. 2014 May;82(5):547-50. doi: 10.1016/j.mehy.2014.02.008. Epub 2014 Feb 14.

Abstract

Recombinant human erythropoietin (rHuEPO) has revolutionized the life of dialysis patients with anemia of chronic kidney disease (CKD). Newer erythropoietin analogues with improved profile have been introduced recently. However, there are many concerns such as safety, economy and patient compliance with these newer rHuEPo analogues. Small molecules aimed to inhibit prolyl hydroxylase domain-2 (PHD2) may prevent degradation of hypoxia inducible factor-2 (HIF2) which leads to endogenous erythropoietin production. This therapeutic intervention may not only overcome the patient compliance and economic burden but also possibly overcome the safety issues related to rHuEPO and its analogues. Moreover, PHD2 inhibitors may increase the endogenous circulating iron availability via suppression of hepcidin, a master regulator of iron homeostasis which further reduces the need for exogenous intravenous iron administration for effective erythropoiesis in renal anemia patients. In conclusion, small molecule PHD2 inhibitors may have better therapeutic efficacy and potential to address clinical concerns associated with rHuEPO and rHuEPO mimetic peptides.

MeSH terms

  • Anemia / drug therapy*
  • Anemia / etiology
  • Enzyme Inhibitors / therapeutic use*
  • Erythropoietin / therapeutic use*
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases / antagonists & inhibitors*
  • Renal Replacement Therapy / adverse effects*

Substances

  • Enzyme Inhibitors
  • Erythropoietin
  • EGLN1 protein, human
  • Hypoxia-Inducible Factor-Proline Dioxygenases