#4856 HISTOLOGICAL FINDINGS OF ACUTE HUMORAL REJECTION IN PATIENTS WITH STANDARD IMMUNOLOGICAL RISK: ANTIBODY-MEDIATED DAMAGE OR MICROVASCULAR INJURY?
Authors: Gavela Eva , Kanter Julia , Aristoy Emma Calatayud , Ávila Ana , Alonso Cristina Castro , Calabuig Maria Asuncion Sancho 
Published: June 2023

Abstract

Background and Aims
The development of acute humoral rejection (AHR) is increased in patients with high immunological risk. Taking into account the highly sensitivity from the techniques used to determine anti-HLA antibodies, the histological findings of AHR in the immediate post-transplantation period in patients without preformed anti-HLA antibodies (standard immunological risk) is unexpected. We propose the implication of non-immunological factors as the origin of these findings. Our aim was to evaluate the histological findings of AHR in the immediate post-transplantation period in patients with standard immunological risk and to analyze factors related to its appearance.

Method
A multicenter retrospective study was carried out including renal transplants performed between January-2014 and december-2022, excluding patients with pre-transplant HLA sensitization and failures due to thrombosis. A descriptive analysis of transplant recipients with standard immunological risk who developed histological findings of AHR was made (AHRh) .In addition, we performed a comparative analysis of this group with the patients who developed AHR with pre-transplant HLA sensitization (AHRs).

Results
Of the 351 patients, 18 (5.1%) presented AHRh, all were first transplants without pre-transplant anti-HLA antibodies. Fourteen donors were brain death and four due to controlled circulatory arrest. Banff AHR was grade I in 1 patient, grade II in 13 patients, and III in 3 cases. 50% showed thrombotic microangiopathy (TMA). Seven (38.9%) failed after a mean follow-up of 28.7±26.1 months. The failure etiologies were chronic rejection (3) and primary dysfunction (4). No patient presented anti-HLA antibodies during the follow-up and 3 have received a second transplant without complications. When comparing the AHRh group with the AHRs (n = 14), we observed a greater age of the donor in AHRh (median 71,5 vs 56.5, p = 0.02) a higher percentage of donor due to controlled circulatory arrest (22% vs 0%, p = 0.075) and with history of Hypertension (66.7% vs 42.9%, p = 0.09). Recipient age was higher in AHRh (median 64.5 vs 51, p = 0.025), with a higher proportion of retransplant in AHRs (42.9% vs 0, p = 0.002). In AHRh, DGF (100% vs 57.1%, p = 0.002) and thrombotic microangiopathy (50% vs 14.3%, p = 0.03) were more frequent. Renal function was worse during the follow-up in AHRh (p&lt;0.05). No differences have been observed in graft and patient survival.

Conclusion
The histological finding of RAH in patients with standard immunological risk appears as an aggressive process with negative consequences on graft survival. The absence of anti-HLA antibodies in subsequent follow-up suggests the involvement of non-immunological factors in its developing. Processes related to the maintenance and/or extraction of organs could favor the appearance of microvascular damage, with histological findings suggestive of AHR especially in older grafts and with comorbidity. Studying these cases is essential to identify risk groups and establish appropriate therapeutic strategies.