Antibody-Mediated Rejection in Kidney Transplantation: From Pathogenesis to Emerging Therapies and Long-Term Graft Outcomes.

Abstract

Background: One of the main causes of kidney allograft dysfunction and late graft failure is antibody-mediated rejection (ABMR). Even with recent improvements in immunosuppressive therapy, donor-specific antibodies (DSAs) still play a major role in causing acute and chronic rejection episodes. The timely and successful diagnosis and treatment of ABMR is critical in maintaining graft function and optimizing transplant outcomes.
Objective: To compare the clinical, treatment, and graft function at follow-up of kidney transplant recipients with ABMR and to determine factors that correlate with graft survival.
Methodology: A prospective study was conducted at Begum Akhtar Rukhsana Memorial Trust and Hospital, Rawalpindi, from June 2022 to November 2022. Fifty kidney transplant recipients with biopsy-confirmed antibody-mediated rejection were enrolled. Demographic characteristics, donor-specific antibody status, serum creatinine, estimated glomerular filtration rate (eGFR), treatment modalities, and graft outcomes were recorded prospectively. Patients received standard treatment including plasmapheresis, intravenous immunoglobulin, corticosteroids, and biologic therapies when indicated. Statistical analysis was performed using SPSS version 26. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages.
Results: A total of 50 kidney transplant recipients with antibody-mediated rejection (ABMR) were included in the study. The mean age of the participants was 42.8 ± 11.6 years, with 31 (62.0%) males and 19 (38.0%) females. Acute ABMR was diagnosed in 32 (64.0%) patients, while 18 (36.0%) had chronic active ABMR. Donor-specific antibodies (DSAs) were detected in 41 (82.0%) recipients. Following treatment, the mean serum creatinine level improved significantly from 2.8 ± 0.9 mg/dL at baseline to 2.1 ± 0.8 mg/dL (p=0.003), while the mean estimated glomerular filtration rate (eGFR) increased from 34.5 ± 12.1 mL/min/1.73 m² to 42.7 ± 13.4 mL/min/1.73 m² (p=0.001). Patients who received combined plasmapheresis and intravenous immunoglobulin (IVIG) therapy demonstrated significantly better graft function compared with other treatment approaches (p=0.021). During the follow-up period, graft survival was achieved in 42 (84.0%) patients, whereas 8 (16.0%) experienced graft loss. Chronic active ABMR and persistent DSAs were identified as significant predictors of adverse graft outcomes (p=0.014 and p=0.008, respectively).
Conclusion: ABMR is still a significant factor in the poor outcomes of kidney transplants. Early recognition, timely therapeutic interventions, and successful DSA suppression are linked to better graft function and survival. New targeted therapies are in development and could further improve long-term allograft results and minimize the risk of graft failure.