Work

#3873 Beyond DSAs: unraveling the complexities of antibody-mediated rejection in kidney transplants

Year: 2025

Type: article

Abstract: Background and Aims Kidney transplantation is the gold standard treatment for end-stage renal disease, significantly improving survival and quality of life compared to dialysis. However, long-term graft survival remains a challenge due to factors like antibody-mediated rejection (AMR). AMR is characterized by the presence of donor-specific antibodies (DSAs), which are integral to both the pathogenesis and diagnosis of rejection. However, not all patients with AMR show detectable DSAs, leading to questions about the role of DSAs in graft loss and patient survival. This study aims to assess the impact of AMR histological changes in patients with and without DSAs. Method This retrospective study included adult kidney transplant patients from two Portuguese centers, focusing on those who exhibited AMR histology. Data on demographics, clinical history, and laboratory results were collected. DSAs and non-donor-specific antibodies (NDSAs) were assessed through Luminex® assays, while histological analysis followed Banff 2019 criteria, focusing on features such as glomerulitis, peritubular capillaritis, and C4d deposition. Statistical tests included the Chi-squared test for categorical variables, the Mann-Whitney U test for continuous variables, and Kaplan-Meier survival analysis for graft and patient survival, with a significance threshold of P < 0.05. Results A total of 27 kidney transplant recipients were included, with a median age of 48.3 years. The cohort consisted of 11 (40.7%) female and 16 (59.3%) male patients. The majority were Caucasian (85.2%), and 22.2% had prior kidney transplants. HLA mismatch analysis showed 51.9% of patients had 2 mismatches for HLA-A, -B, and -DR, and 40.7% had 4 mismatches, as indicated in Fig. 1. Donors were mostly male (51.9%), with 33.3% being expanded criteria donors. Seven patients (25.9%) had preformed DSAs. Induction therapy included basiliximab (51.9%) and thymoglobulin (37%), while 96.3% of patients received tacrolimus, mycophenolate mofetil, and prednisone for maintenance. Of the patients, 74.1% were DSA-positive, 22.2% had NDSAs, and 3.7% had neither. Graft loss occurred in 7 DSA-positive patients (35%) compared to 1 (16.7%) in the NDSA group, and mortality was observed in 2 DSA-positive patients (10%) but in none of the NDSA group. However, these differences were not statistically significant (graft loss P = 0.554, mortality P = 0.685). Figure 2 summarizes baseline characteristics by DSA status. Histological analysis showed acute AMR in 70.4%, with no significant differences in AMR between the DSA-positive and -negative groups (P = 0.277). Regarding rejection treatment, patients treated with MPD + IVIG had a significantly higher mortality rate (P = 0.014). Graft loss was significantly associated with male donors (P = 0.016) and Class I DSAs (P = 0.038). At the time of rejection, the median serum creatinine was 3.4 mg/dL, decreasing to 2.075 mg/dL at 6 months and 2.160 mg/dL by the end of follow-up. DSA-positive patients had a significantly lower creatinine at rejection (2.705 mg/dL vs 4.800 mg/dL, P = 0.048), but no significant differences were observed after 6 months (P = 0.377) or at the end of follow-up (P = 0.311). Conclusion This study highlights the complexity of AMR in kidney transplantation, showing that DSA presence alone may not predict graft loss or mortality. Microvascular inflammation and other histopathological changes, as well as donor characteristics, also play a significant role in long-term outcomes. Further research is needed to identify additional biomarkers and refine therapeutic strategies, particularly for DSA-negative patients, to improve graft survival and reduce rejection risk. Enhanced monitoring and individualized treatment regimens based on a patient's immunological and histopathological profile are essential for optimizing AMR management.

Source: Nephrology Dialysis Transplantation

DOI: 10.1093/ndt/gfaf116.0818