*Purpose: International guidelines indicate Living Donor Kidney Transplantation (LDKT) as the best option for ESRD patients. Immunological barriers like AB0 incompatibility (AB0i) and donor specific antibodies (DSAs) against donor’s HLA antigens represent the main hitch to LDKT. In order to overcome these immunological barriers and to spread LKDT, there are two main strategies: desensitization therapy and Kidney Paired Donation (KPD) Programs.

*Methods: In our Center both these strategies are applied, PKD since 2005 and AB0i and DSA desensitization protocols for direct transplantation since 2009. This study analyzes the outcomes in 54 patients transplanted between 2005 and 2017 applying the KPD strategy (n=21; 10 AB0i, 8 DSA and 3 AB0i+DSA) or the desensitization therapy (n=33; 10 AB0i, 18 DSA and 5 AB0i+DSA) followed by similar maintenance immunosuppressive therapy, and compares the results of the main groups: KPD vs desensitization and those of the subgroups stratified according reasons for incompatibility: AB0i vs DSA. All the groups were comparable for recipient and donor characteristics at baseline without statistical differences in the main demographics, pathological, and surgical parameters.

*Results: Any significant differences between the KPD group and the desensitization one in term of patient survival and graft survival were recorded: patient survival rates at 1 and 4 years after LKDT are 100% and 97% in the desensitization group and 100% and 95% in the KPD one; graft survival rates at 1 and 4 years after LKDT are 100% and 91% in the desensitization group and 100% and 100% in the KPD one. There are also no significant differences in term of clinical complications during postoperative period and follow-up. No significant differences have been detected in the comparison between the AB0i and DSA subgroups in the desensitization and in the KPD group. The analysis of the immunological profile during follow-up shows that LKDTx DSA desensitized patients are more prone to produce denovo DSA and when they are high titer DSA (>3,000 mfi) recipients have higher risk of acute rejection (50% vs 14%). Cost analysis highlights a significant difference: desensitization strategies involve an additional cost equal to three months of dialysis.

*Conclusions: We propose a decisional algorithm including and integrating both strategies in an unique flowchart that gives priority in any cases to the KPD for couples with DSAs. In case of AB0i, results of direct LKDTx after desensitization protocols or KPD are comparable differing only for cost, however reasonable if compared to dialysis prolongation waiting for a compatible KPD over 3 months.

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