title: Thrombotic microangiopathy in renal allografts: the diagnostic challenge.
abstract: OBJECTIVE
  The diagnosis of thrombotic microangiopathy (TMA) is complex and often difficult. This review provides an approach to the diagnosis with emphasis on recent relevant developments.
  
  
  RESULTS
  There is increasing evidence that most cases of recurrent TMA in renal allografts are secondary to mutations in genes encoding complement regulatory factors and complement components, such as factor H, factor I, membrane cofactor protein, C3, and others. Genetic work-up for these potential complement abnormalities is now available and recommended. Another important cause for recurrent TMA is the presence of autoantibodies, such as antibodies to factor H and antiphospholipid antibodies. De-novo TMA is much more common than recurrent TMA in renal allografts. De-novo TMA can be secondary to calcineurin inhibitor treatment, mammalian target of rapamycin inhibitor treatment, but frequently also to antibody-mediated rejection and less commonly to infections. Systemic signs of TMA are often absent, and the gold standard for diagnosis is the renal allograft biopsy. Unfortunately, diagnostic criteria for TMA are somewhat subjective, and the biopsy provides limited information regarding the exact underlying cause.
  
  
  CONCLUSIONS
  TMA is a serious complication of renal transplantation, usually with poor outcome. However, with improving understanding of underlying pathogeneses, more effective disease-specific therapeutic interventions can be designed. Appropriate treatment depends on the correct diagnosis, which relies primarily on renal allograft biopsy. Standardization of pathologic criteria and introduction of new molecular testing methods in renal biopsy specimens hopefully will improve diagnostic accuracy.
authors.affiliation: Department of Pathology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Tibor
authors.initials: T
authors.lastname: Nadasdy
mesh_terms: D064591:Allografts; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D057049:Thrombotic Microangiopathies / Q000175:diagnosis* / Q000517:prevention & control; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents