**6. Treatment**

There has been significant development of newer and more specific therapies for ABMR. These are aimed at depleting B cells, antibodies and inhibiting complement, owing to the unique role of antibody and effector molecules in the process of ABMR. The therapeutic options include intensification of maintenance immunosuppression (e.g. tacrolimus and mycophenolate), plasmapheresis/plasma exchange, intravenous immunoglobulin (IVIg), corticosteroids and antilymphocyte antibodies. Rituximab, splenectomy, bortezomib, and eculizumab have also emerged as adjunctive or experimental therapies.

depletion with rituximab as an induction agent had significant reductions in DSA generation and rates of chronic transplant glomerulopathy over 5 years compared with ABO-compatible

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Drugs that inhibit compliment and C1 are likely to show benefit in the prevention and treatment of ABMR and currently they are many human trials being conducted to evaluate

Eculizumab is an antibody against complement protein C5, and hence, inhibits the formation of the membrane attack complex (MAC). It is approved for use in paroxysmal nocturnal hemoglobinuria (PNH) and has had promising results in treatment and ongoing management of atypical haemolytic uraemic syndrome, for which it has also recently been approved for use. It is, however, and extremely expensive therapy. A single case reported the use of eculizumab in combination with plasmapheresis/IVIg to rescue a renal allograft undergoing severe ABMR, and showed significant reduction in C5b-C9 (MAC) complex deposition in the

The role of splenectomy in treating ABMR is not yet known. Case reports have demonstrated that it may be useful as a rescue treatment in severe ABMR.[53] Majority of its use has been in preventing hyperacute rejection in ABOI transplants [54, 55]. There remains concern over the increased infection risk in splenectomised patients, particularly due to encapsulated organ‐ isms, and vaccination against Meningococcus and Pneumococcus is warranted where possible

Significant progress has occurred in the understanding of ABMR. Diagnosis, classification and treatment of this process have evolved greatly. However, standardisation of diagnostic tests (DSA-testing), and development of evidence-based treatment guidelines is still lacking. Currently, protocols are individualised among different centres and based largely on anecdotal and/or local experience. ABOI and HLA desensitisation protocols (not detailed in this chapter) also need to gain excellent long term results to justify the tremendous cost involved in order to reduce the growing number of sensitised potential recipients on the waiting list. Paired donor exchange programs, although fraught with major logistic as well as some ethical and occasionally legal concerns, may be part of the solution to provide allografts to some of these difficult-to-transplant individuals in order to improve their quality and quantity of life. Such recipients, after successful transplantation, will be at increased risk of ABMR and will need

good monitoring and treatment strategies to enable successful long-term outcomes.

low-risk transplant recipients who did not receive rituximab.[50]

**6.4. Eculizumab**

their effect.[3, 51]

kidney.[52]

**6.5. Splenectomy**

**7. Conclusion**

prior to splenectomy to mitigate this risk.
