噬血细胞性淋巴组织细胞增多症（HLH）是一种免疫功能障碍，其特征是过度的病理性炎症反应，可能导致全身炎症反应和多器官衰竭，包括肾脏受累。 HLH 可分为原发性或继发性，原发性 HLH 与影响细胞脱颗粒能力的基因突变有关，继发性 HLH 通常与感染、肿瘤和自身免疫性疾病有关。 HLH 的发病机制尚不完全清楚，但原发性 HLH 通常由遗传缺陷驱动，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，因此很难与严重脓毒症特别是感染引起的继发性 HLH 区分开来。共同特征包括长期发热、肝脾肿大、血减少、肝功能障碍、高甘油三酯血症和低纤维蛋白原血症，以及组织细胞增多症和噬血细胞增多症。然而，双重血细胞减少症、高甘油三酯血症、低纤维蛋白原血症和 sCD25 水平升高等独特标志物可能有助于区分 HLH 和脓毒症。事实上，没有单一的生物标志物可以有效地区分噬血细胞性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为鉴别诊断提供了见解。 HLH 和脓毒症中经常会出现肾功能损害。它可能是由炎症介质涌入引发的全身炎症反应、这些因素造成的直接损伤或原发性疾病过程的结果引起的。例如，巨噬细胞浸润肾脏可导致结构损伤，影响肾脏的各个组成部分，从而引发疾病。目前，肾小管坏死仍然是 HLH 相关急性肾损伤 (HLH-AKI) 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、显微镜下病变和血栓性微血管病。 HLH 和脓毒症的治疗方法存在显着差异。 HLH 主要通过重复化疗来治疗，以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于抗感染治疗和强化对症支持治疗。肾功能显着影响临床决策，特别是化疗和抗生素剂量的选择，这可以深刻影响患者的预后。相反，肾功能恢复是一个复杂的过程，受疾病严重程度、诊断及时性和治疗强度等因素的影响。管理 HLH-AKI 的一个重要方面是及时诊断，这在逆转肾功能损害和创造干预治疗窗口方面发挥着关键作用，可能有机会改善患者预后。了解急性肾损伤相关噬血细胞性淋巴组织细胞增多症 (HLH-AKI) 的临床特征、根本原因、生物标志物、免疫发病机制和治疗选择对于改善患者预后至关重要。版权所有 © 2024 赵、关、林、邱、赵和段。

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.Copyright © 2024 Zhao, Guan, Lin, Qiu, Zhao and Duan.