Sethi Sanjeev, Fervenza Fernando C, Rajkumar S Vincent
aDivision of Anatomic Pathology, Department of Laboratory Medicine and Pathology bDivision of Hypertension and Nephrology, Department of Internal Medicine cDivision of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Curr Opin Nephrol Hypertens. 2016 Mar;25(2):127-37. doi: 10.1097/MNH.0000000000000201.
Monoclonal gammopathies result from an overt malignant process, such as multiple myeloma, or a premalignant process, such as monoclonal gammopathy of undetermined significance. The kidney is often affected in the setting of a monoclonal gammopathy. The term 'monoclonal gammopathy of renal significance (MGRS)' was recently introduced to draw attention to renal diseases related to the monoclonal gammopathy. In this review, we define the pathology of these monoclonal gammopathy-associated kidney diseases.
Renal disease can be caused by deposition of the monoclonal immunoglobulin (direct mechanism) or by activation of the alternative pathway of complement by the monoclonal immunoglobulin (indirect mechanism). The deposition of monoclonal immunoglobulin can affect the glomeruli, tubules, and the interstitium and vessels. The glomerular diseases include proliferative glomerulonephritis with monoclonal immunoglobulin deposits, immunotactoid glomerulopathy, and, less commonly, fibrillary glomerulonephritis. Tubular lesions associated with monoclonal immunoglobulin include cast nephropathy and light-chain proximal tubulopathy. Lesions involving the glomeruli, tubules, interstitium or vessels include amyloidosis and monoclonal immunoglobulin deposition diseases. Rarely, monoclonal immunoglobulin may also cause C3 glomerulopathy or atypical hemolytic uremic syndrome by interfering with the regulation of the alternative pathway of complement.
Monoclonal gammopathy are associated with a variety of kidney diseases. The monoclonal gammopathy-associated renal diseases are distinct in their pathogenesis, kidney biopsy findings, clinical presentation, progression, prognosis, and treatment. The term monoclonal gammopathy of renal significance helps highlight patients who have renal disease secondary to monoclonal immunoglobulin secreted by a premalignant or malignant clone, but is not a disease or diagnosis in itself.
综述目的：单克隆丙种球蛋白病可由明显的恶性过程引起，如多发性骨髓瘤，或癌前过程，如意义未明的单克隆丙种球蛋白病。肾脏在单克隆丙种球蛋白病的情况下常受影响。最近引入了“具有肾脏意义的单克隆丙种球蛋白病（MGRS）”这一术语，以引起人们对与单克隆丙种球蛋白病相关的肾脏疾病的关注。在本综述中，我们定义了这些与单克隆丙种球蛋白病相关的肾脏疾病的病理学。
最新发现：肾脏疾病可由单克隆免疫球蛋白的沉积（直接机制）或单克隆免疫球蛋白激活补体替代途径（间接机制）引起。单克隆免疫球蛋白的沉积可影响肾小球、肾小管、间质和血管。肾小球疾病包括伴有单克隆免疫球蛋白沉积的增殖性肾小球肾炎、免疫触须样肾小球病，较少见的还有纤维样肾小球肾炎。与单克隆免疫球蛋白相关的肾小管病变包括管型肾病和轻链近端肾小管病。累及肾小球、肾小管、间质或血管的病变包括淀粉样变性和单克隆免疫球蛋白沉积病。很少见的是，单克隆免疫球蛋白也可能通过干扰补体替代途径的调节而导致C3肾小球病或非典型溶血尿毒综合征。
总结：单克隆丙种球蛋白病与多种肾脏疾病相关。与单克隆丙种球蛋白病相关的肾脏疾病在发病机制、肾脏活检结果、临床表现、进展、预后和治疗方面各不相同。具有肾脏意义的单克隆丙种球蛋白病这一术语有助于突出那些因癌前或恶性克隆分泌的单克隆免疫球蛋白而继发肾脏疾病的患者，但它本身并不是一种疾病或诊断。
