Post-transplant Thrombotic Microangiopathy.
Thrombotic microangiopathy complicates 0.8%-15% of kidney transplants and significantly affects graft and patient survival; distinguishing complement-mediated disease from other triggers is critical, because complement-mediated TMA does not respond to supportive care, needs long-term anticomplement therapy and carries a high risk of recurrence.
Background
Thrombotic microangiopathy (TMA) is a challenging and serious complication of kidney transplantation, occurring in 0.8%-15% of transplant recipients and significantly affecting graft and patient survival. It is characterized by microangiopathic haemolytic anaemia, thrombocytopenia and organ injury caused by endothelial damage and microthrombus formation in small vessels. Clinical features range from a renal-limited form diagnosed only on kidney biopsy to full systemic manifestations including neurologic, gastrointestinal and cardiovascular injury.
Mechanisms and causes
TMA can arise from genetic or acquired defects, as in complement-mediated TMA, or occur in the context of infections, autoimmune diseases or immunosuppressive drugs, where complement activation may also play a role. Recurrent TMA after kidney transplant is almost always complement-mediated. Complement overactivation may also contribute to de novo post-transplant TMA associated with ischaemia-reperfusion injury, immunosuppressive drugs, antibody-mediated rejection, viral infections and relapse of autoimmune disease such as antiphospholipid antibody syndrome. TMA associated with non-complement genes, often part of a broader syndromic process with distinct clinical features, has also been described.
Clinical implications
Differentiating a complement-mediated process from one triggered by other factors is often challenging but critical to minimize allograft damage, because the former is unresponsive to supportive therapy, requires long-term anticomplement therapy and carries a high risk of recurrence. Given the central role of complement and the effect of genetic defects on recurrence risk, genetic testing for complement disorders is key to proper diagnosis and management. Because complement activation may also contribute to a subset of TMAs associated with other conditions, prompt recognition and timely initiation of anticomplement therapy is equally important, and early identification and treatment are essential to prevent graft failure and other severe complications.
Category
Transplant
Source
J Am Soc Nephrol
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