Kokoris Styliani I, Gavriilaki Eleni, Miari Aggeliki, Travlou Αnthi, Kyriakou Elias, Anagnostopoulos Achilles, Grouzi Elissavet
a Laboratory of Hematology and Hospital Blood Transfusion Department , University General Hospital 'Attikon', Medical School, National and Kapodistrian University of Athens , Chaidari Attica , Greece.
b Hematology Department-BMT Unit , G. Papanicolaou Hospital , Thessaloniki , Greece.
Hematology. 2018 Sep;23(8):558-566. doi: 10.1080/10245332.2018.1444563. Epub 2018 Feb 28.
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.
A thorough PubMed search was performed using as main keywords: 'paroxysmal nocturnal hemoglobinuria', 'acute kidney injury', 'chronic kidney disease' and 'eculizumab'.
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.
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.
Understanding the difficult but at the same time impressive mechanisms behind PNH remains a challenge for treating physicians.
本综述总结了阵发性睡眠性血红蛋白尿（PNH）患者急性和慢性肾功能不全的现有知识，重点关注其临床特征、病理生理学和治疗。
使用“阵发性睡眠性血红蛋白尿”“急性肾损伤”“慢性肾病”和“依库珠单抗”作为主要关键词，在PubMed上进行全面检索。
PNH的发病机制基于获得性突变，导致CD55和CD59补体调节因子减少或缺失，这些因子是该疾病一些主要临床特征的原因，如血管内溶血、血细胞减少和血栓形成。PNH常常诊断不足，主要是由于其偶尔出现的轻微表现以及它模拟其他严重临床病症的能力。对于因游离血红素和游离铁释放导致的肾损伤，已提出多种机制，包括炎症反应、氧化应激、一氧化氮耗竭、肾缺血、膜损伤和细胞凋亡。依库珠单抗是一种末端补体抑制剂，提供了一种安全有效的治疗选择，尤其是在肾损伤早期开始使用时。
肾损伤是PNH研究较少的临床特征，影响相当一部分患者。医生需要提高认识，以识别急性和慢性肾功能不全的早期体征和症状，从而启动必要的治疗。在疾病过程中重新评估PNH特异性治疗也很重要。
理解PNH背后艰难但同时令人印象深刻的机制对治疗医生来说仍然是一项挑战。
