噬血细胞性淋巴组织细胞增生症(HLH)是一种以过度和病理性炎症反应为特征的免疫功能障碍,可能导致全身炎症反应和多器官功能衰竭,包括肾脏受累.HLH可以分为原发性或继发性,与影响细胞脱颗粒能力的基因突变相关的原发性HLH,继发性HLH通常与感染有关,肿瘤,和自身免疫性疾病。HLH的发病机制尚不完全清楚,但是原发性HLH通常是由遗传缺陷驱动的,而继发性HLH涉及CD8+T细胞和巨噬细胞的激活,导致炎症细胞因子的释放和全身炎症反应综合征(SIRS)。HLH的临床表现包括非特异性表现,这使得区分严重的败血症具有挑战性,特别是继发性HLH由于感染。共同特征包括长时间发烧,肝脾肿大,血细胞减少症,肝功能障碍,高甘油三酯血症,和低纤维蛋白原血症,伴随着组织细胞增多和噬血细胞增多。然而,独特的标志物,如双重血细胞减少症,高甘油三酯血症,低纤维蛋白原血症,和升高的sCD25水平可能有助于区分HLH和脓毒症。的确,没有单一的生物标志物能有效区分噬血细胞淋巴组织细胞增多症和感染.然而,对组合生物标志物的研究提供了对鉴别诊断的见解。在HLH和脓毒症中经常遇到肾功能损害。它可能是由炎症介质的涌入引发的全身性炎症反应引起的,这些因素造成的直接损害,或作为主要疾病过程的结果。例如,肾脏的巨噬细胞浸润可导致影响各种肾脏成分的结构损伤,诱发疾病。目前,在HLH相关急性肾损伤(HLH-AKI)中,肾小管坏死仍然是肾脏受累的主要形式.然而,组织病理学变化也可能包括间质性炎症,肾小球异常,微观病变,和血栓性微血管病.HLH和脓毒症的治疗方法存在显著差异。HLH主要通过重复化疗来消除免疫激活刺激并抑制细胞过多。脓毒症的治疗方法主要集中在抗感染治疗和强化对症支持治疗。肾功能显著影响临床决策,特别是关于化疗和抗生素剂量的选择,会对患者预后产生深远的影响。相反,肾功能恢复是一个复杂的过程,受疾病严重程度等因素的影响,及时诊断,以及治疗的强度。管理HLH-AKI的一个关键方面是及时诊断,它在逆转肾功能损害和创造干预治疗窗口中起着关键作用,可能有机会改善患者预后。了解临床特征,根本原因,生物标志物,免疫发病机制,与急性肾损伤相关的噬血细胞性淋巴组织细胞增多症(HLH-AKI)的治疗选择对于改善患者预后至关重要。
Hemophagocytic lymphohistiocytosis (HLH) is an immune dysfunction characterized by an exaggerated and pathological inflammatory response, potentially leading to systemic inflammatory reactions and multiple-organ failure, including renal involvement. HLH can be classified as primary or secondary, with primary HLH associated with genetic mutations affecting cell degranulation capacity, and secondary HLH often linked to infections, tumors, and autoimmune diseases. The pathogenesis of HLH is not fully understood, but primary HLH is typically driven by genetic defects, whereas secondary HLH involves the activation of CD8+ T cells and macrophages, leading to the release of inflammatory cytokines and systemic inflammatory response syndrome (SIRS). The clinical presentation of HLH includes non-specific manifestations, making it challenging to differentiate from severe sepsis, particularly secondary HLH due to infections. Shared features include prolonged fever, hepatosplenomegaly, hematopenia, hepatic dysfunction, hypertriglyceridemia, and hypofibrinogenemia, along with histiocytosis and hemophagocytosis. However, distinctive markers like dual hemocytopenia, hypertriglyceridemia, hypofibrinogenemia, and elevated sCD25 levels may aid in differentiating HLH from sepsis. Indeed, no singular biomarker effectively distinguishes between hemophagocytic lymphohistiocytosis and infection. However, research on combined biomarkers provides insights into the differential diagnosis. Renal impairment is frequently encountered in both HLH and sepsis. It can result from a systemic inflammatory response triggered by an influx of inflammatory mediators, from direct damage caused by these factors, or as a consequence of the primary disease process. For instance, macrophage infiltration of the kidney can lead to structural damage affecting various renal components, precipitating disease. Presently, tubular necrosis remains the predominant form of renal involvement in HLH-associated acute kidney injury (HLH-AKI). However, histopathological changes may also encompass interstitial inflammation, glomerular abnormalities, microscopic lesions, and thrombotic microangiopathy. Treatment approaches for HLH and sepsis diverge significantly. HLH is primarily managed with repeated chemotherapy to eliminate immune-activating stimuli and suppress hypercellularity. The treatment approach for sepsis primarily focuses on anti-infective therapy and intensive symptomatic supportive care. Renal function significantly influences clinical decision-making, particularly regarding the selection of chemotherapy and antibiotic dosages, which can profoundly impact patient prognosis. Conversely, renal function recovery is a complex process influenced by factors such as disease severity, timely diagnosis, and the intensity of treatment. A crucial aspect in managing HLH-AKI is the timely diagnosis, which plays a pivotal role in reversing renal impairment and creating a therapeutic window for intervention, may have opportunity to improve patient prognosis. Understanding the clinical characteristics, underlying causes, biomarkers, immunopathogenesis, and treatment options for hemophagocytic lymphohistiocytosis associated with acute kidney injury (HLH-AKI) is crucial for improving patient prognosis.