Styliani I Kokoris1, Eleni Gavriilaki2, Aggeliki Miari3, Αnthi Travlou3,4, Elias Kyriakou1, Achilles Anagnostopoulos2, Elissavet Grouzi5. 1. a Laboratory of Hematology and Hospital Blood Transfusion Department , University General Hospital 'Attikon', Medical School, National and Kapodistrian University of Athens , Chaidari Attica , Greece. 2. b Hematology Department-BMT Unit , G. Papanicolaou Hospital , Thessaloniki , Greece. 3. c Medical School , University of Athens , Athens , Greece. 4. d Laboratory of Thrombosis, Bleeding Disorders and Anticoagulation Monitoring , Medical Centre of Psychico , Athens , Greece. 5. e Department of Transfusion Service and Clinical Hemostasis , 'Saint Savvas' Oncology Hospital , Athens , Greece.
Abstract
OBJECTIVES: The present review summarizes the available knowledge regarding acute and chronic kidney dysfunction in patients with paroxysmal nocturnal hemoglobinuria (PNH) focusing on its clinical features, pathophysiology and treatment. METHODS: A thorough PubMed search was performed using as main keywords: 'paroxysmal nocturnal hemoglobinuria', 'acute kidney injury', 'chronic kidney disease' and 'eculizumab'. RESULTS: PNH's etiopathogenesis is based on acquired mutations that lead to the reduction or absence of CD55 and CD59 complement regulators, which are responsible for some of the disease's major clinical features, like intravascular hemolysis, cytopenias and thrombosis. PNH is often underdiagnosed, mainly due to its occasional mild manifestations and to its ability to mimic other severe clinical conditions. Various mechanisms have been proposed for the kidney damage attributed to the release of cell-free heme and free iron, including inflammatory response, oxidative stress, nitric oxide depletion, renal ischemia, membrane damage and apoptosis. Eculizumab, a terminal complement inhibitor, provides a safe and effective treatment option, especially when it is initiated early in the presence of kidney damage. DISCUSSION: Kidney injury is a poorly investigated clinical feature of PNH that affects a significant portion of patients. Increased awareness is needed by physicians to recognize the early signs and symptoms of acute and chronic renal insufficiency, so as to initiate the necessary therapy. It is also important to re-evaluation of PNH-specific treatments during the course of the disease. CONCLUSION: Understanding the difficult but at the same time impressive mechanisms behind PNH remains a challenge for treating physicians.
OBJECTIVES: The present review summarizes the available knowledge regarding acute and chronic kidney dysfunction in patients with paroxysmal nocturnal hemoglobinuria (PNH) focusing on its clinical features, pathophysiology and treatment. METHODS: A thorough PubMed search was performed using as main keywords: 'paroxysmal nocturnal hemoglobinuria', 'acute kidney injury', 'chronic kidney disease' and 'eculizumab'. RESULTS: PNH's etiopathogenesis is based on acquired mutations that lead to the reduction or absence of CD55 and CD59 complement regulators, which are responsible for some of the disease's major clinical features, like intravascular hemolysis, cytopenias and thrombosis. PNH is often underdiagnosed, mainly due to its occasional mild manifestations and to its ability to mimic other severe clinical conditions. Various mechanisms have been proposed for the kidney damage attributed to the release of cell-free heme and free iron, including inflammatory response, oxidative stress, nitric oxide depletion, renal ischemia, membrane damage and apoptosis. Eculizumab, a terminal complement inhibitor, provides a safe and effective treatment option, especially when it is initiated early in the presence of kidney damage. DISCUSSION: Kidney injury is a poorly investigated clinical feature of PNH that affects a significant portion of patients. Increased awareness is needed by physicians to recognize the early signs and symptoms of acute and chronic renal insufficiency, so as to initiate the necessary therapy. It is also important to re-evaluation of PNH-specific treatments during the course of the disease. CONCLUSION: Understanding the difficult but at the same time impressive mechanisms behind PNH remains a challenge for treating physicians.
Authors: Anna Felberg; Aleksandra Urban; Anna Borowska; Grzegorz Stasiłojć; Michał Taszner; Andrzej Hellmann; Anna Maria Blom; Marcin Okrój Journal: Cancer Immunol Immunother Date: 2019-02-06 Impact factor: 6.968
Authors: M Jalink; E C W de Boer; D Evers; M Q Havinga; J M I Vos; S Zeerleder; M de Haas; I Jongerius Journal: Semin Immunopathol Date: 2021-06-30 Impact factor: 9.623