ABO incompatible kidney transplantations have previously only been performed after several preoperative sessions of plasmapheresis and splenectomy, with the conventional triple-drug immunosuppressive protocol being reinforced with antilymphocyte globulin and Bcell-specific drugs, such as cyclophosphamide or deoxyspergualine. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. The protocol calls for a 10-day pretransplantation conditioning period, starting with one dosage of rituximab and followed by full dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pretransplantation days −6, −5, −2 and −1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. Furthermore, if there was a significant increase in the antibody titers, extra sessions were considered. Eleven patients have received transplants with this protocol. The ABO antibodies were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects and all patients have normal renal transplant function. We conclude that after an infusion each of rituximab and IVIG, and antigen-specific immunoadsorption; blood groupincompatible renal transplantations can be performed with excellent results using standard immunosuppression and no splenectomy.

We conclude that after one infusion each of rituximab and intravenous immunoglobulin and antigen-specific immunoadsorption, blood-group-incompatible renal transplantations can be performed with standard immunosuppression and without splenectomy.

Background. Atypical haemolytic uraemic syndrome (aHUS) is a rare, life-threatening disorder for which eculizumab is the only approved treatment. Life-long treatment is indicated; however, eculizumab discontinuation has been reported. Methods. Unpublished authors’ cases and published cases of eculizumab discontinuation are reviewed. We also report eculizumab discontinuation data from five clinical trials, plus long-term extensions and the global aHUS Registry. Results. Of six unpublished authors’ cases, four patients had a subsequent thrombotic microangiopathy (TMA) manifestation within 12 months of discontinuation. Case reports of 52 patients discontinuing eculizumab were identified; 16 (31%) had a subsequent TMA manifestation. In eculizumab clinical trials, 61/130 patients discontinued treatment between 2008 and 2015. Median follow-up post-discontinuation was 24 weeks and during this time 12 patients experienced 15 severe TMA complications and 9 of the 12 patients restarted eculizumab. TMA complications occurred irrespective of identified genetic mutation, high risk polymorphism or auto-antibody. In the global aHUS Registry, 76/296 patients (26%) discontinued, 12 (16%) of whom restarted. Conclusions. The currently available evidence suggests TMA manifestations following discontinuation are unpredictable in both severity and timing. For evidence-based decision making, better risk stratification and valid monitoring strategies are required. Until these exist, the risk versus benefit of eculizumab discontinuation, either in specific clinical situations or at selected time points, should include consideration of the risk of further TMA manifestations.

Leukocyte apheresis is a novel and safe nonpharmacological adjunct therapy that may prove useful in steroid refractory or dependent patients when conventional drugs have failed. Down-regulation of IFN-gamma in mucosal biopsies and in peripheral leukocytes may be a predictive marker for sustained, long-term response.