Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA; Division of Nephrology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Kidney Int. 2024 Dec;106(6):1062-1071. doi: 10.1016/j.kint.2024.07.036. Epub 2024 Sep 18.
Clonal monocytosis reflects a preneoplastic or neoplastic sustained increase in the absolute monocyte count in the absence of reactive causes. Causes of clonal monocytosis include clonal cytopenias with monocytosis and acute and chronic myeloid neoplasms. Chronic myelomonocytic leukemia is a prototypical myelodysplastic/myeloproliferative overlap neoplasm in adults, characterized by sustained peripheral blood monocytosis. Kidney abnormalities, including acute kidney injury and chronic kidney disease, are frequent in patients with chronic myelomonocytic leukemia and are predictors of worse outcomes. In addition, acute kidney injury/chronic kidney disease often limits eligibility for allogeneic stem cell transplantation or enrollment in clinical trials. In this review, we highlight clonal monocytosis-related etiologies that give rise to acute kidney injury and chronic kidney disease, with special emphasis on chronic myelomonocytic leukemia and lysozyme-induced nephropathy. Monocytes produce lysozyme, which, in excess, can accumulate in and damage the proximal renal tubular epithelium. Early identification of this etiology and a timely reduction in monocyte counts can salvage kidney function. Other etiologies of kidney injury associated with clonal monocytosis include direct renal infiltration by monocytes, renal extramedullary hematopoiesis, myeloproliferative neoplasm-associated glomerulopathy, autoimmune (membranous nephropathy, minimal change disease) and paraneoplastic manifestations, thrombotic microangiopathy, obstructive nephropathy due to myeloproliferation, and urate nephropathy due to tumor lysis syndrome. We propose to group these mechanistic etiologies of kidney injury as clonal monocytosis of renal significance and provide guidance on their diagnosis and management.
克隆性单核细胞增多症反映了在不存在反应性原因的情况下，绝对单核细胞计数持续增加的肿瘤前或肿瘤性疾病。克隆性单核细胞增多症的病因包括伴有单核细胞增多的克隆性血细胞减少症以及急性和慢性髓系肿瘤。慢性髓系单核细胞白血病是一种典型的成人骨髓增生异常/骨髓增殖性肿瘤重叠疾病，其特征为外周血单核细胞持续增多。肾脏异常，包括急性肾损伤和慢性肾脏病，在慢性髓系单核细胞白血病患者中很常见，并且是预后不良的预测因素。此外，急性肾损伤/慢性肾脏病常限制异体干细胞移植或临床试验的入组资格。在这篇综述中，我们强调了与克隆性单核细胞增多症相关的病因，这些病因可导致急性肾损伤和慢性肾脏病，特别强调了慢性髓系单核细胞白血病和溶菌酶诱导的肾病。单核细胞产生溶菌酶，过多的溶菌酶会在近端肾小管上皮细胞内积聚并造成损伤。早期识别这种病因并及时降低单核细胞计数可以挽救肾功能。与克隆性单核细胞增多症相关的其他肾脏损伤病因包括单核细胞对肾脏的直接浸润、肾髓外造血、骨髓增生性肿瘤相关肾小球病、自身免疫性疾病（膜性肾病、微小病变病）和副肿瘤表现、血栓性微血管病、骨髓增生引起的梗阻性肾病以及肿瘤溶解综合征引起的尿酸肾病。我们建议将这些与克隆性单核细胞增多症相关的肾脏损伤机制病因归为具有肾脏意义的克隆性单核细胞增多症，并提供其诊断和管理的指导。
