Alpers Charles E, Smith Kelly D
Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
Curr Opin Nephrol Hypertens. 2008 May;17(3):243-9. doi: 10.1097/MNH.0b013e3282f8afe2.
Cryoglobulinemia occurs in a variety of clinical settings including lymphoproliferative disorders, infection and autoimmune disease. The worldwide pandemic of hepatitis C virus infection has resulted in a significant increase in its extrahepatic complications including cryoglobulinemia and renal disease. Here we review the types of cryoglobulins, mechanisms of cryoglobulin formation, links between hepatitis C virus and renal disease, and current approaches to therapy.
The prevalence of cryoglobulinemia in hepatitis C virus-infected individuals is surprisingly large and may be found in more than 50% of some infected subpopulations. Most of these patients will not have overt renal disease, but there is a population of unknown size of patients with subclinical glomerular disease that has the potential to become clinically significant. In cases of hepatitis C virus-associated cryoglobulinemia, treatment remains focused on eradication of viremia, but interventions directed at B lymphocytes are increasingly utilized. The mechanisms of cryoglobulin formation and renal injury remain largely obscure, but recent evidence implicates the innate immune system in the initiation of disease.
The most common renal injury associated with hepatitis C virus infection, in patients both with and without evidence of cryoglobulinemia, is membranoproliferative glomerulonephritis. There has been increasing focus on defining the mechanisms that link these processes and the evolution of renal injury in all clinical settings of cryoglobulinemia.
冷球蛋白血症发生于多种临床情况,包括淋巴增殖性疾病、感染及自身免疫性疾病。丙型肝炎病毒感染的全球大流行导致其肝外并发症显著增加,包括冷球蛋白血症和肾脏疾病。在此,我们综述冷球蛋白的类型、冷球蛋白形成机制、丙型肝炎病毒与肾脏疾病的关联以及当前的治疗方法。
丙型肝炎病毒感染个体中冷球蛋白血症的患病率惊人地高,在某些受感染亚群中可能超过50%。这些患者大多不会有明显的肾脏疾病,但有一部分亚临床肾小球疾病患者数量不明,他们有发展为具有临床意义疾病的可能。在丙型肝炎病毒相关冷球蛋白血症病例中,治疗仍主要集中于清除病毒血症,但针对B淋巴细胞的干预措施使用得越来越多。冷球蛋白形成和肾损伤的机制在很大程度上仍不清楚,但最近的证据表明先天性免疫系统在疾病起始中起作用。
在有和没有冷球蛋白血症证据的丙型肝炎病毒感染患者中,最常见的肾损伤是膜增生性肾小球肾炎。人们越来越关注确定在冷球蛋白血症的所有临床情况下将这些过程与肾损伤演变联系起来的机制。