Korean J Transplant.  2023 Mar;37(1):11-18. 10.4285/kjt.23.0011.

Characteristics and management of thrombotic microangiopathy in kidney transplantation

• Cho W
• Jo SK
• Jung CW
• Kim MG

• KMID: 2541308
• DOI: http://doi.org/10.4285/kjt.23.0011

Abstract

Thrombotic microangiopathy is not a rare complication of kidney transplantation and is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury with extensive thrombosis of the arterioles and capillaries. Various factors can cause thrombotic microangiopathy after kidney transplantation, including surgery, warm and cold ischemia-reperfusion injury, exposure to immunosuppressants, infection, and rejection. Many recent studies on atypical hemolytic uremic syndrome have described genetic abnormalities related to excessive activation of the alternative complement pathway. The affected patients’ genetic backgrounds revealed significant genetic heterogeneity in several genes involved in complement regulation, including the complement factor H, complement factor H-related proteins, complement factor I, complement factor B, complement component 3, and CD46 genes in the alternative complement pathway. Although clinical studies have provided a better understanding of the pathogenesis of diseases, the diverse triggers present in the transplant environment can lead to thrombotic microangiopathy, along with various genetic predispositions, and it is difficult to identify the genetic background in various clinical conditions. Given the poor prognosis of posttransplant thrombotic microangiopathy, further research is necessary to improve the diagnosis and treatment protocols based on risk factors or genetic predisposition, and to develop new therapeutic agents.

Keyword

Thrombotic microangiopathy; Atypical hemolytic uremic syndrome; Kidney transplantation

Figure

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  Fig. 1 Diagnostic algorithm and therapeutic options for posttransplant TMA. If TMA of unknown cause occurs after kidney transplantation or recurrent TMA is observed, ADAMTS13 and Shiga toxin assay tests need to be performed to differentiate aHUS from TTP and STEC-HUS, along with genetic testing, and consider early initiation of eculizumab. If secondary TMA is suspected, trigger management should be performed first, but if there is no response to treatment for the secondary cause or if plasmapheresis-dependent patterns are observed, the diagnosis and treatment of aHUS should be considered. TMA, thrombotic microangiopathy; PPx, plasma exchange; ABMR, antibody-mediated rejection; RTX, rituximab; IVIG, intravenous immune globulin; STEC, Shiga toxin-producing Escherichia coli; MCP, membrane cofactor protein; CFH, complement factor H; CFI, complement factor I; CFB, complement factor B; THBD, thrombomodulin; TTP, thrombotic thrombocytopenic purpura; HUS, hemolytic uremic syndrome; aHUS, atypical HUS.

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