**Author details**

In the absence of large randomized controlled trials, the optimal desensitization protocol is unclear. Observational data have reported desensitization protocols comprising of high or low-dose IVIg and plasmapheresis with or without rituximab and othetr newer agents such as bortezomib and eculizumab may be beneficial in selected patients, the rate of AMR remains extremely high (up to 50% in pre-sensitized positive cross-match patients undergoing desensitization) and may not be justified in circumstances such as in patients with very strong pre-transplant DSA levels [19]. The lack of treatment effectiveness among highly sensitised individuals is not unexpected, because most recommended treatment options such as plas‐ mapheresis, IVIg and rituximab have minimal effects on plasma cells, the critical element of anti-HLA antibodies production, and AMR. Clinicians should discuss with their patients about the complexities and the potential side effects associated with any desensitisation protocols, taking into considerations the underlying immunological risks of the potential transplant candidates, the potential benefits against the short and longer-term harms such as infection and cancer risks. Specifically transplant candidates with prior sensitizing events and have DSA (even at low levels) against potential donor (e.g. husband to wife transplant) are at significant risk of AMR after transplantation despite r adequate desensitization. If desensitization is undertaken, this should be initiated 2-3 weeks post-transplant to ensure adequate removal of anti-HLA DSA pre-transplant with at least a negative CDC cross-match (or reduction in flow cytometric cross-match results) and persistent reduction in DSA MFI below 2000-5000. Transplantation should be abandoned if there is rebound of high titres DSA and/or the crossmatches remained unchanged/positive following desensitisation protocols. Although the benefit or cost-effectiveness of post-transplant DSA monitoring ± protocol biopsies in improv‐ ing post-transplant graft outcomes remains unclear, it is well established that *de novo* DSA and rising pre-transplant DSA are associated with a greater risk of rejection and poorer graft survival [32, 92, 93]. However, there is no data suggesting that early interventions in renal transplant recipients who develop *de novo* DSA or rising DSA would result in an improvement in graft outcomes. Nevertheless, prospective monitoring of pre-existing DSA or for *de novo* DSA ± protocol biopsies should be considered and appropriate treatment instituted in those who develop histological evidence of rejection. Several proposed desensitization and posttransplant follow-up algorithms for positive cross-match highly sensitized recipients are available but the cost-effectiveness and outcomes of these programs remains unknown [80].

122 Current Issues and Future Direction in Kidney Transplantation

Despite the availability of more potent immunosuppression, the incidence of AMR continues to be an important cause of graft loss. Nevertheless, with the evolution of more sensitive molecular-based HLA-typing and the ability to detect DSA, clinicians have the necessary facts to critically appraise the immunological risk of each transplant candidate. However, there continues to be debate on several major issues including the role of non-DSA in transplantation, the appropriate DSA threshold, complexity in the diagnosis of acute and chronic AMR and the optimal desensitization protocol for highly sensitized patients. As there continues to be an increase in the number of highly sensitized renal transplant candidates on the transplant wait-

**7. Conclusion**

Shyam Dheda1,2, Siew Chong1 , Rebecca Lucy Williams1 , Germaine Wong3 and Wai Hon Lim1,2\*

\*Address all correspondence to: wai.lim@health.wa.gov.au

1 Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia

2 School of Medicine and Pharmacology, University of Western Australia, Perth, Australia

3 Sydney School of Public Health, University of Sydney; Centre for Kidney Research, The Children's Hospital at Westmead; Centre for Transplant and Renal Research, Westmead Hospital, Sydney, Australia
