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肾移植后新发肾小球疾病

De novo glomerular diseases after renal transplantation.

作者信息

Ponticelli Claudio, Moroni Gabriella, Glassock Richard J

机构信息

Division of Nephrology, Humanitas Scientific Institute, Rozzano, Milan, Italy;

Division of Nephrology, Fondazione Ca' Granda Ospedale Maggiore Istituto Scientifico, Milan, Italy; and.

出版信息

Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1479-87. doi: 10.2215/CJN.12571213. Epub 2014 Apr 3.

Abstract

Glomerular diseases developing in the kidney allograft are more often recurrences of the original disease affecting the native kidneys. However, in an undefined number of cases de novo, glomerular diseases unrelated to the original disease in the native kidneys can develop in the transplanted kidney. The clinical presentation and histologic features of de novo diseases are often similar to those features observed in patients with primary or secondary GN in the native kidneys. However, in transplanted kidneys, the glomerular, vascular, and tubulointerstitial changes are often intertwined with structural abnormalities already present at the time of transplant or caused by antibody- or cell-mediated allograft rejection, immunosuppressive drugs, or superimposed infection (most often of a viral nature). The pathophysiology of de novo glomerular diseases is quite variable. In rare cases of de novo minimal change disease, circulating factors increasing the glomerular permeability likely participate. Maladaptive hemodynamic changes and tissue fibrosis caused by calcineurin inhibitors or other factors may be involved in the pathogenesis of de novo FSGS. The exposure of cryptic podocyte antigens may favor the development of de novo membranous nephropathy. Many cases of de novo membranoproliferative GN are related to hepatitis C virus infection. Patients with Alport syndrome lacking antigenic epitopes in their glomerular basement membrane may develop antibodies against these glomerular basement membrane antigens expressed in the transplanted kidney. Infection may cause acute GN to have a heterogeneous clinical presentation and outcome. De novo pauci-immune GN in renal transplant is rare. Preexisting or acquired intolerance to glucose may, in the long term, cause diabetic nephropathy. The prognosis of de novo diseases depends on the type of GN, the severity of lesions caused by the alloimmune response, or the efficacy of immunosuppressive therapy. In most cases, the management of de novo glomerular diseases is empirical or elusive.

摘要

同种异体肾移植中发生的肾小球疾病更多是原发病累及自身肾脏后的复发。然而,在数量不明的病例中,移植肾可发生与自身肾脏原发病无关的新发肾小球疾病。新发疾病的临床表现和组织学特征通常与自身肾脏原发性或继发性肾小球肾炎患者所观察到的特征相似。然而,在移植肾中,肾小球、血管和肾小管间质的变化常常与移植时已存在的结构异常相互交织,或由抗体或细胞介导的移植排斥反应、免疫抑制药物或叠加感染(最常见的是病毒感染)所致。新发肾小球疾病的病理生理学变化很大。在罕见的新发微小病变病病例中,可能有增加肾小球通透性的循环因子参与其中。钙调神经磷酸酶抑制剂或其他因素引起的适应性血流动力学变化和组织纤维化可能参与新发局灶节段性肾小球硬化的发病机制。隐蔽足细胞抗原的暴露可能有利于新发膜性肾病的发生。许多新发膜增生性肾小球肾炎病例与丙型肝炎病毒感染有关。患有Alport综合征且其肾小球基底膜缺乏抗原表位的患者,可能会产生针对移植肾中表达的这些肾小球基底膜抗原的抗体。感染可能导致急性肾小球肾炎出现异质性临床表现和预后。肾移植中新发寡免疫性肾小球肾炎很少见。长期存在的或后天获得的葡萄糖不耐受可能会导致糖尿病肾病。新发疾病的预后取决于肾小球肾炎的类型、同种免疫反应引起的病变严重程度或免疫抑制治疗的疗效。在大多数情况下,新发肾小球疾病的治疗是经验性的或难以捉摸的。

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