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

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

The Limits of Paired Donation: Who Doesnt Get Transplanted?

Deceased Donor List

9000 cPRA>95%

Transplant Rates by cPRA 4400/6 mos

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

Paired Donation

63% cPRA>95% National Kidney Registry

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

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

Figure 1 Time (Days) cPRA

cPRA by MFI

Phase II KPD + Desensitization PatientcPRA (%) Waiting time (days) Transplant group Desensitization (Y/N) B-Flow XM Original Intended Donor N Paired DonorN Paired DonorY Deceased Donor N Original Intended Donor Y Deceased Donor Y Paired DonorY Original Intended Donor Y Paired DonorN Original Intended Donor Y316 Recipients with cPRA >90 who received a Transplant in Phase 2

Phase II KPD + Desensitization 10 cPRA >95% transplanted

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

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

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

Conclusions Sensitized patients have more transplant options than before

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

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

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

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