1. Desensitization in the Era of Kidney Paired Donation Mark D. Stegall, M.D.

2. Institution : Mayo Clinic, Rochester. Research contracts with Alexion and Millenium My presentation includes discussion of off-label and investigational. YesEculizumab, Alexion Pharmaceuticals; Disclosure.

3. The Limits of Paired Donation: Who Doesnt Get Transplanted?

4. Deceased Donor List

5. 9000 cPRA>95%

6. Transplant Rates by cPRA 4400/6 mos

7. Actual Death-Censored 5 Year Graft Survival 70.7% vs 88.0%, p= 0.0006

8. Paired Donation

9. 63% cPRA>95% National Kidney Registry

10. Mayo Foundation 3-Site KPD Program Cooperative: virtually one cost center and one protocol Screen multiple donors (HLA type) and do full workup when a chain emerges Cooperative: virtually one cost center and one protocol Screen multiple donors (HLA type) and do full workup when a chain emerges

11. Two Eras Phase I: Avoid desensitization Accept +XM up to channel shift of 200 (3000 MFI or so) 8/2009-12/2012 (90 KPDs) Phase II: Allow desensitization 3 months is KPD If no chain, then allow +XMKTx with desentization 1/2013--present Phase I: Avoid desensitization Accept +XM up to channel shift of 200 (3000 MFI or so) 8/2009-12/2012 (90 KPDs) Phase II: Allow desensitization 3 months is KPD If no chain, then allow +XMKTx with desentization 1/2013--present

12. Figure 1 Time (Days) cPRA

13. cPRA by MFI

14. Phase II KPD + Desensitization PatientcPRA (%) Waiting time (days) Transplant group Desensitization (Y/N) B-Flow XM 199495 Original Intended Donor N123 2991018Paired DonorN191 3991019Paired DonorY305 4991147 Deceased Donor N0 599187 Original Intended Donor Y160 699723 Deceased Donor Y206 7991263Paired DonorY215 891428 Original Intended Donor Y248 99520Paired DonorN137 1099236 Original Intended Donor Y316 Recipients with cPRA >90 who received a Transplant in Phase 2

15. Phase II KPD + Desensitization 10 cPRA >95% transplanted

16. Phase II KPD + Desensitization 10 cPRA >95% transplanted 4 KPD 2 no desensitization 2 desensitization (lower +XM)

17. Phase II KPD + Desensitization 10 cPRA >95% transplanted 4 KPD 2 no desensitization 2 desensitization (lower +XM) 4 original donor

18. Phase II KPD + Desensitization 10 cPRA >95% transplanted 4 KPD 2 no desensitization 2 desensitization (lower +XM) 4 original donor 2 deceased donors

19. Conclusions Sensitized patients have more transplant options than before

20. Conclusions Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation

21. Conclusions Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation Donor with lowest level of antibody is the next best option Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation Donor with lowest level of antibody is the next best option

22. Conclusions Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation Donor with lowest level of antibody is the next best option +Crossmatch Kidney Transplant may be the only viable option Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation Donor with lowest level of antibody is the next best option +Crossmatch Kidney Transplant may be the only viable option

23. Conclusions Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation Donor with lowest level of antibody is the next best option +Crossmatch Kidney Transplant may be the only viable option New therapies are needed to control antibody and its effects on the kidney transplant Sensitized patients have more transplant options than before Donor without antibody is idealpaired donation/deceased donation Donor with lowest level of antibody is the next best option +Crossmatch Kidney Transplant may be the only viable option New therapies are needed to control antibody and its effects on the kidney transplant