Peak DSA Levels Pre-Transplant but Not at Transplant Predict Graft Survival

A. Y. Choi¹, D. Olaso¹, T. Risoli Jr², M. Kuchibhatla², Z. Fitch³, R. Schmitz³, P. M. Schroder³, A. Jackson³, M. Manook³, J. Yoon³, A. B. Farris⁴, J. Kwun³, S. J. Knechtle³

¹Duke University School of Medicine, Durham, NC, ²Duke Biostatistics, Epidemiology, and Research Design Core, Duke University, Durham, NC, ³Department of Surgery, Duke University Medical Center, Durham, NC, ⁴Department of Pathology, Emory University Hospital, Atlanta, GA

Meeting: 2020 American Transplant Congress

Abstract number: 574

Keywords: Antibodies, Graft failure, Kidney transplantation, Primates

Session Information

Session Name: Kidney Immunosuppression: Desensitization

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

Presentation Time: 4:27pm-4:39pm

Location: Virtual

*Purpose: Immunization to major histocompatibility complex (MHC) antigens is a barrier in kidney transplantation (KTx) due to higher risk of antibody-mediated rejection (AMR) and graft loss. Desensitization regimens aim to reduce donor-specific antibodies (DSA) prior to KTx. We examined correlations between pre-transplant DSA and KTx outcomes in nonhuman primates.

*Methods: Maximally MHC mismatched rhesus macaques (n=41) were sensitized with 2 sequential skin transplants. Primates were desensitized with experimental protocols including carfilzomib (CFZ), CFZ+tocilizumab, CFZ+daratumumab+plerixafor, CFZ+tabalumab, CFZ+anti-CD28dAb, and CFZ+belatacept. Serum DSA was measured by flow crossmatch (FXM). We defined peak DSA as the highest level measured after the second skin transplant and calculated the change from peak DSA to DSA at KTx. We used the log-rank test to compare graft survival among peak DSA quartiles (Kaplan-Meier curves). We used Spearman correlations to characterize the relationship between DSA and both graft survival and AMR severity (clustered Banff, g+ptc+C4d).

*Results: Graft survival varied significantly among peak DSA quartiles (log-rank p<0.001, Figure 1A). Greater drop in DSA levels prior to KTx correlated with shorter graft survival in both T cell and B cell FXM (r_s = -0.59, p<0.001 and r_s = -0.48, p=0.002). Peak DSA levels and change in DSA from peak to time of KTx negatively correlated with AMR severity. Finally, DSA levels at KTx did not significantly correlate with graft survival or AMR severity (r_s= -0.29, p=0.13; log-rank p=0.112, Figure 1B).

*Conclusions: DSA levels negatively correlated with graft survival and AMR severity. Under pharmacologic influence, the magnitude and change in DSA levels between sensitization and KTx may be a better prognostic tool than DSA levels at KTx. Given differences in regimens and timelines in this cohort, these findings deserve further investigation.

To cite this abstract in AMA style:

Choi AY, Olaso D, Jr TRisoli, Kuchibhatla M, Fitch Z, Schmitz R, Schroder PM, Jackson A, Manook M, Yoon J, Farris AB, Kwun J, Knechtle SJ. Peak DSA Levels Pre-Transplant but Not at Transplant Predict Graft Survival [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/peak-dsa-levels-pre-transplant-but-not-at-transplant-predict-graft-survival/. Accessed November 21, 2024.

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