Abstract
Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired genetic disorder characterized by complement-mediated haemolysis, thrombosis and variable cytopenias. Renal involvement may occur and causes significant morbidity to these patients. To review the literature about pathophysiology and provide recommendations on diagnosis and management of renal involvement in PNH. Online research in the Medline database with compilation of the most relevant 26 studies found. PNH may present with acute kidney injury caused by massive haemolysis, which is usually very severe. In the chronic setting, PNH may develop insidious decline in renal function caused by tubular deposits of hemosiderin, renal micro-infarcts and interstitial fibrosis. Although hematopoietic stem cell transplantation remains the only curative treatment for PNH, the drug Eculizumab, a humanized anti-C5 monoclonal antibody is capable of improving renal function, among other outcomes, by inhibiting C5 cleavage with the subsequent inhibition of the terminal complement pathway which would ultimately give rise to the assembly of the membrane attack complex. There is a lack of information in literature regarding renal involvement in PNH, albeit it is possible to state that the pathophysiological mechanisms of acute and chronic impairment differ. Despite not being a curative therapy, Eculizumab is able to ease kidney lesions in these patients.
Highlights
Paroxysmal nocturnal haemoglobinuria (PNH) is a haematological condition classically characterized by chronic haemolysis and thrombotic events
A review of literature was performed in the Medline (PubMed) database, using the following keywords: paroxysmal nocturnal haemoglobinuria; renal involvement; renal injury; Eculizumab; pathogenesis. 26 articles considered by us the most relevant were obtained from the Commission for Improvement of Higher Education Personnel (Comissão de Aperfeiçoamento de Pessoal de Nível Superior – CAPES) online source
Besides PIG-A gene mutation, any other genetic abnormality impairing proper synthesis of GPI-anchored proteins (GPI-AP) may lead to PNH, with many possible genetic mutations reported in literature
Summary
Paroxysmal nocturnal haemoglobinuria (PNH) is a haematological condition classically characterized by chronic haemolysis and thrombotic events. RENAL INVOLVEMENT IN PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA: A BRIEF REVIEW OF THE LITERATURE deficiency of two of those extracellular proteins is relevant in PNH: CD55 and CD59. Both proteins are responsible to prevent complement-mediated RBCs opsonization and lysis. Most of the kidney impairment in PNH stems from chronic haemolysis, free haemoglobin (Hb) release in the bloodstream, and subsequent Hb renal filtration. Magnetic resonance imaging (MRI) may evidence cortical renal haemosiderosis caused by chronic haemolysis and haemoglobin filtration[5]. In the development of PNH-related CKD, renal thrombotic events apparently play an even more important role than Hb filtration[5]
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