Complement Inhibition Therapy and Dialytic Strategies in Paroxysmal Nocturnal Hemoglobinuria: The Nephrologist's Opinion.

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease that presents an estimated incidence of 1.3 cases per million per year, with a prevalence of 15.9 cases per million. It is characterized by hemolysis, bone marrow dysfunction with peripheral blood cytopenia, hypercoagulability, thrombosis, renal impairment and arterial and pulmonary hypertension. Hemolysis and subsequent hemosiderin accumulation in tubular epithelium cells induce tubular atrophy and interstitial fibrosis. The origin of PNH is the somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene located on Xp22: this condition leads to the production of clonal blood cells with a deficiency in those surface proteins that protect against the lytic action of the activated complement system. Despite the increased knowledge of this syndrome, therapies for PNH were still only experimental and symptomatic, until the introduction of the C5 complement blockade agent Eculizumab. A second generation of anti-complement agents is currently under investigation, representing future promising therapeutic strategies for patients affected by PNH. In the case of chronic hemolysis and renal iron deposition, a multidisciplinary approach should be considered to avoid or treat acute tubular injury or acute kidney injury (AKI). New promising perspectives derive from complement inhibitors and iron chelators, as well as more invasive treatments such as immunoadsorption or the use of dedicated hemodialysis filters in the presence of AKI.