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  • Title: De novo thrombotic microangiopathy after kidney transplantation.
    Author: Garg N, Rennke HG, Pavlakis M, Zandi-Nejad K.
    Journal: Transplant Rev (Orlando); 2018 Jan; 32(1):58-68. PubMed ID: 29157988.
    Abstract:
    Thrombotic microangiopathy (TMA) is a serious complication of transplantation that adversely affects kidney transplant recipient and allograft survival. Post-transplant TMA is usually classified into two categories: 1) recurrent TMA and 2) de novo TMA. Atypical hemolytic uremic syndrome (aHUS) resulting from dysregulation and over-activation of the alternate complement pathway is a rare disease but the most common diagnosis associated with recurrence in the allografts. De novo TMA, on the other hand, represents an overwhelming majority of the cases of post-transplant TMA and is a substantially more heterogeneous entity than recurrent aHUS. Here, we review the etio-pathogenesis, diagnosis and treatment options for de novo post-transplant TMA. It is usually in the setting of calcineurin inhibitor use, mammalian target of rapamycin inhibitor use, or antibody mediated rejection; recently genetic mutations in complement regulatory genes for Factor H and Factor I similar to those described in aHUS have been reported in up to a third of these patients. Systemic signs of TMA are frequently absent, and a renal allograft biopsy is often needed to establish the diagnosis. Although withdrawal of the offending agents is usually the first line of treatment and resolution of laboratory abnormalities has been documented with this approach in several case reports and case series, available retrospective data demonstrate lack of benefit in long-term graft outcomes. Co-stimulation blockage with belatacept provides an effective alternate immunosuppressive strategy for these patients. Anti-complement therapy with eculizumab is effective in some cases; further work is required to define which patients with TMA (with and without concomitant antibody-mediated rejection) would benefit from receiving this treatment, and what biomarkers can be used to identify them.
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