Atypical HUS associated with severe, unexpected antibody-mediated rejection post kidney transplant

Journal Publication ResearchOnline@JCU
Stevenson, Sarah;Mallett, Andrew;Oliver, Kimberley;Hyland, Valentine;Hawley, Carmel;de Malmanche, Theo;Isbel, Nicole
Abstract

We present a case of an unsensitized patient with end-stage kidney disease secondary to atypical haemolytic uremic syndrome (aHUS) with mutations in CD46/MCP and CFH who developed severe, intractable antibodymediated rejection (ABMR) unresponsive to therapy post kidney transplantation. There were no haematological features of thrombotic microangiopathy. The patient received standard induction therapy and after an initial fall in serum creatinine, severe ABMR developed in the setting of urosepsis. Despite maximal therapy with thymoglobulin, plasma exchange and methylprednisolone, rapid graft loss resulted and transplant nephrectomy was performed. Luminex at 4 weeks showed a new DSA and when repeated after nephrectomy showed antibodies to each of the 5 mismatched antigens with high MFI. The rate of recurrence of disease in patients with aHUS referred for transplantation is 50% and is associated with a high rate of graft loss. It is dependent in part on the nature of the mutation with circulating factors CFH and CFI more likely to cause recurrent disease than MCP which is highly expressed in the kidney. There is increasing interest in the role of complement in the development and propagation of ABMR via terminal complement activation. This case suggesting that dysregulation of the alternative complement pathway within the transplant kidney may have contributed to the severe AMR. Very little is known about the impact of complement dysregulation and the development of anti HLA antibodies however the strength of HLA antibody formation was prominent in this case.

Journal

Nephrology

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Volume

19

ISBN/ISSN

1440-1797

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Issue

S1

Pages Count

5

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Publisher

Wiley-Blackwell Publishing Asia

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DOI

10.1111/nep.12195