Kidney Transplantation: A New Perioperative Approach for Presensitized Recipients

Kidney transplantation is a surgical procedure where a healthy kidney from a donor is transplanted into a patient with end-stage renal disease (ESRD). ESRD is the final stage of chronic kidney disease, where the kidneys can no longer support the body’s needs. The transplanted kidney takes over the functions of the failing kidneys, including filtering waste products, balancing electrolytes, and regulating blood pressure. Presensitization in kidney transplantation refers to the presence of pre-existing antibodies in a recipient, directed against human leukocyte antigens (HLAs) of the donor. These antibodies can develop due to previous exposures to foreign HLAs through blood transfusions, pregnancies, or prior transplants. Presensitized recipients have an elevated Panel Reactive Antibody (PRA) level, indicating a heightened immune response against donor organs. the presence of presensitized recipients presents unique and significant challenges in transplant medicine. Managing these challenges requires specialized approaches to immunosuppression, donor-recipient matching, and monitoring to improve outcomes for these high-risk patients. To address these challenges, a new study published in Frontiers in Immunology by Zhiliang Guo, Daqiang Zhao, Rula Sa, Lu Wang, Songxia Li, Guangyuan Zhao, Lan Zhu, and led by Professor Gang Chen from the Institute of Organ Transplantation at Huazhong University of Science and Technology, the researchers conducted a retrospective study to evaluate a modified perioperative regimen for deceased donor kidney transplantation in presensitized recipients without prior desensitization therapy.

The clinical research team included 51 PRA-positive recipients and 62 control recipients who underwent deceased donor renal transplantation. The presensitized group was further divided based on donor-specific antibody (DSA) status into DSA-positive and DSA-negative subgroups. The presensitized patients, regardless of DSA status, received a modified perioperative treatment starting on day 0 or -1, which included:

Rituximab: A single dose preoperatively.

Thymoglobulin: Administered as induction therapy over five days.

Intravenous Immunoglobulin (IVIG): Administered at low daily doses (10-20 g/d) for 14 days.

For DSA-positive recipients, the authors performed plasmapheresis once before the surgery. This approach was designed to manage the risk of antibody-mediated rejection (AMR) which is higher in presensitized patients, particularly those with DSA. They monitored post-transplant, DSA levels weekly for the first month, and renal biopsies were considered based on changes in DSA levels and renal graft function. Additional plasmapheresis/IVIG therapy was provided to patients with biopsy-diagnosed AMR or those with persistently high DSA levels affecting renal function recovery.

The researchers reported higher incidences of early acute rejection and AMR in the presensitized group, especially in the DSA-positive subgroup. All rejections were successfully reversed with the treatment protocol. Moreover, stable graft function was maintained during the follow-up period and the survival rates for grafts and recipients in the presensitized group were notably high at 98%.

The authors concluded that with the new modified IVIG-based perioperative regimen, excellent intermediate-term graft and recipient survival outcomes can be achieved in presensitized patients who receive deceased donor kidney transplantation without prior desensitization.

The study’s outcomes are groundbreaking. The modified regimen demonstrated not only the feasibility but also the effectiveness of conducting deceased donor kidney transplantation in presensitized patients, who traditionally face daunting prospects due to the high risk of AMR. This approach opens new doors for a demographic that has historically been marginalized in transplant medicine, offering them hope and a viable path to transplantation. The clinical study highlights the importance of a comprehensive AMR management strategy in presensitized recipients. The utilization of a modified IVIG-based perioperative regimen was pivotal in achieving favorable outcomes. This research is significant as it offers a viable and effective strategy for managing high-risk transplant recipients, potentially transforming clinical practices in the field of transplant immunology.