Introduction: Sensitization to human leukocyte antigen (HLA) resulting from pregnancy, blood transfusions, or prior transplantation is a significant impediment to kidney transplantation (KT). Our previous report outlined a phased desensitization strategy using rituximab, followed by bortezomib, and demonstrated its safety in highly sensitized kidney transplant candidates. Herein, we present the medium- and long-term outcomes of patients who underwent KT according to our desensitization protocol.
Methods: Between January 2009 and December 2018, 25 crossmatch (XM)-positive kidney transplant candidates underwent desensitization therapy. Patient demographics, sensitization history, XM results, and mean fluorescent intensity (MFI) of donor-specific antibodies (DSAs) values were examined. Our desensitization regimen initially comprised rituximab (RTX), tacrolimus, and mycophenolate mofetil, followed by double-filtration plasmapheresis (DFPP). KT was performed if the patients remained XM-negative and the DSA MFI decreased. For patients that were persistently XM-positive with an increased DSA MFI, bortezomib (BTZ) was administered after RTX administration upon B cell recovery. KT was performed if the patients remained XM-negative, with repeat BTZ administration for those that were positive.
Results: No serious complications related to the desensitization therapy were observed. Fifteen of the 25 patients successfully underwent KT after desensitization. Among the patients that underwent transplantation, 11 were female, 6 had undergone prior transplantation, and 11 received organs from their spouses. The MFI values of DSAs ranged from 4,000 to 20,000, and eight patients tested positive for CDC-XM. Six patients were desensitized using RTX alone, whereas nine received BTZ. Patients with prior transplants and high DSA MFI values typically required BTZ, especially HLA class II DSA-positive patients (who required multiple doses of BTZ). Desensitization was difficult to achieve in patients with DSA MFI values greater than 18,000 and male recipients with a history of transplantation. Successful desensitization and KT were achieved in all patients with pregnancy-associated sensitization. Following our desensitization therapy, the death-censored graft survival rates were 100% at 5 years and 88% at 10 years, whereas the patient survival rates were 93% at 5 years and 80% at 10 years.
Conclusion: Although the short-term outcomes of KT after desensitization using our approach are promising, it is imperative to improve mid-to-long-term outcomes. Novel treatment modalities are warranted for patients for whom desensitization is difficult to achieve.