Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity.

Ana Ávila,Asunción Sancho,Eva Gavela

doi:10.3389/fmed.2021.642864

Abstract

Thrombotic microangiopathy is a rare but serious complication that affects kidney transplant recipients. It appears in 0.8–14% of transplanted patients and negatively affects graft and patient survival. It can appear in a systemic form, with hemolytic microangiopathic anemia, thrombocytopenia, and renal failure, or in a localized form, with progressive renal failure, proteinuria, or arterial hypertension. Post-transplant thrombotic microangiopathy is classified as recurrent atypical hemolytic uremic syndrome or de novo thrombotic microangiopathy. De novo thrombotic microangiopathy accounts for the majority of cases. Distinguishing between the 2 conditions can be difficult, given there is an overlap between them. Complement overactivation is the cornerstone of all post-transplant thrombotic microangiopathies, and has been demonstrated in the context of organ procurement, ischemia-reperfusion phenomena, immunosuppressive drugs, antibody-mediated rejection, viral infections, and post-transplant relapse of antiphospholipid antibody syndrome. Although treatment of the causative agents is usually the first line of treatment, this approach might not be sufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve renal function. Complement blockade with eculizumab has been shown to be an effective therapy in post-transplant thrombotic microangiopathy, but it is necessary to define which patients can benefit from this therapy and when and how eculizumab should be used.

Highlights

Thrombotic microangiopathy (TMA) is a life-threatening disease, characterized by endothelial dysfunction and the presence of thrombi in small blood vessels
Post-transplant Thrombotic Microangiopathy or acquired abnormalities in complement proteins leading to unregulated activation of the alternative pathway of the complement system and the formation of the membrane attack complex (MAC) [11, 12]
Secondary TMA syndromes occur in the context of infections, organ transplantation, drugs, malignancies, pregnancy, malignant hypertension, and autoimmune diseases [3, 5, 6]

Summary

INTRODUCTION

Thrombotic microangiopathy (TMA) is a life-threatening disease, characterized by endothelial dysfunction and the presence of thrombi in small blood vessels. Post-transplant Thrombotic Microangiopathy or acquired abnormalities in complement proteins leading to unregulated activation of the alternative pathway of the complement system and the formation of the membrane attack complex (MAC) [11, 12] Other genetic causes, such as diacylglycerol kinase ε, an endothelial cell and podocyte protein, and cobalamin C deficiency have been described as causes of primary aHUS, mainly in children [13, 14]. Post-transplant thrombotic microangiopathy (PT-TMA) is a rare but devastating condition that can lead to poor patient and graft outcomes. It can occur as a de novo disease or as a recurrence of a previous aHUS (sometimes undiagnosed before kidney transplantation).

Caused by complement protein mutations: atypical hemolytic uremic syndrome

16 Early 6 Late

Findings

CONCLUSION