Thrombotic microangiopathy after renal transplantation: Current insights in de novo and recurrent disease

Abstract

Thrombotic microangiopathy (TMA) is one of the most devastating sequalae of kidney transplantation. A number of published articles have covered either de novo or recurrent TMA in an isolated manner. We have, hereby, in this article endeavored to address both types of TMA in a comparative mode. We appreciate that de novo TMA is more common and its prognosis is poorer than recurrent TMA; the latter has a genetic background, with mutations that impact disease behavior and, consequently, allograft and patient survival. Post-transplant TMA can occur as a recurrence of the disease involving the native kidney or as de novo disease with no evidence of previous involvement before transplant. While atypical hemolytic uremic syndrome is a rare disease that results from complement dysregulation with alternative pathway overactivity, de novo TMA is a heterogenous set of various etiologies and constitutes the vast majority of post-transplant TMA cases. Management of both diseases varies from simple maneuvers, e.g., plasmapheresis, drug withdrawal or dose modification, to lifelong complement blockade, which is rather costly. Careful donor selection and proper recipient preparation, including complete genetic screening, would be a pragmatic approach. Novel therapies, e.g., purified products of the deficient genes, though promising in theory, are not yet of proven value.

Keywords: Kidney transplantation; De novo thrombotic microangiopathy; Thrombotic microangiopathy; Recurrent thrombotic microangiopathy; Atypical hemolytic uremic syndrome

Core tip: Many articles in the literature have covered either de novo or recurrent thrombotic microangiopathy (TMA) in an isolated manner; we tried here in this article to gather the criteria of both types in one review for comparison. Contrary to what was believed in the past, de novo TMA is more common and its prognosis is poorer. On the other hand, recurrent TMA relies on a wide base of genetic backgrounds, with mutation errors differing in their impact on disease behavior and consequently on allograft and patient survival. This base for instance is rapidly expanding, and ultimately warrants a parallel robust work up regimen.