J. Lambdin1, N. Koizumi2, K. Mahendran1, J. K. Melancon1 1George Washington University School Of Medicine And Health Sciences,Transplant Institute And Division Of Transplant Surgery,Washington, DC, USA 2George Mason University,School Of Policy, Government And International Affairs,Arlington, VIRGINIA, USA
Introduction: Over 100 000 candidates await a kidney transplant on the national United Network for Organ Sharing (UNOS) waitlist. Among these candidates, one-third have preformed antibodies against human leukocyte antigens (HLA). These patients fall under the category of high risk kidney transplantation compared to non-sensitized patients. Those patients: 1) undergoing ABO incompatible kidney transplant; 2) with donor specific antibodies; 3) with a low level of nonspecific antibodies; or 4) with a prior transplant/s also fall into this category. These high risk transplant recipients demonstrate a higher rate of delay graft function and graft failure.
Our objective was to demonstrate that our unique Bortezomib based desensitization protocol could be an effective induction therapy among high risk kidney transplant candidates to reduce delayed graft function and acute antibody mediated rejections. Our hypothesis is that humoral responses has been an underappreciated culprit in both delayed graft function and as an interface with cell medicated rejection responses. Bortezomib's anti humoral mechanism we belive to be an important adjunct in the immunospressive armamentraium.
Methods: A total of 126 patients underwent deceased-donor kidney transplants at our center between 01/01/2015 and 04/23/2018. Of these, 65 patients received Bortezomib based induction therapy as they were high risk candidates. All patients were given maintenance immunosuppression with Tacrolimus, Mycophenolate Mofetil and Prednisone as per standard of care, regardless of their risk stratification. The outcomes were assessed based on: 1) occurrence of delayed graft function; and 2) presence of protocol biopsy proven rejection; and 3) graft survival. Using the UNOS data, we performed a propensity score analysis to extract high risk transplant recipients from the SRTR national transplant database who are similar to the recipients who received the Bortezomib based induction therapy at our center. Logistic regression and survival analyses were performed to compare the outcomes between the intervention recipients and the matched sample.
Results: The Bortezomib based desensitization therapy was effective (p=0.01) in the matched sample analysis. Adjusting for the common covariates and the propensity score, those recipients who received the therapy was about 36% less likely to experience a delayed graft function.
Conclusion: We conclude that our Bortezomib based desensitization/induction therapy decreases delayed graft function in high risk kidney transplant recipients. We belive that this will impact very favorably on the long term graft and patient survial.