Donor-Specific Antibodies in Renal Transplantation and Their Impact on Kidney Graft Survival

Donor-specific HLA antibodies (DSA) has been associated with an increased risk of rejection and poorer graft outcomes.Short-term survival following desensitization has been demonstrated with acceptable outcomes.The medium-term graft survival in Uruguay has not been studied. The objective  is analyze the impact of pre-existing DSA in renal transplantation (RT) on medium-term graft survival (SV) and  in the incidence of acute rejection (AR).

A retrospective cohort study was conducted at 2 RT centers in Uruguay, involving 476 patients who underwent RT from January 2016 to May 2021. Patients under 15 years old and those with combined transplants were excluded. All  underwent HLA antibody studies using Luminex with mean fluorescence intensity (MFI), negative crossmatch by XM , and ABO-compatible grouping. Demographic data of recipients, donors, immunosuppression, and RT outcomes were recorded. AR was defined within the first 3 months of RT based on Banff 2019 criteria; graft loss was defined as a return to dialysis, and severe infection requiring hospitalization within the first 12 months of RT. SV was analyzed using Kaplan-Meier, and multivariate analysis was performed using logistic regression for SV and AR risk factors.

476 RT were divided into Group1: Pre-existing DSA positive (11%, n: 52) vs. Group 2: DSA negative (89%, n: 419).

No differences were observed between groups in  post-RT follow-up time (G1 39±25 months vs. G2 41±20 months), recipient age (G1 45±11 vs. G2 48±15 years), donor age (G1 37±15 vs. G2 41±16 years), and cold ischemia time (G1 18 hours vs. G2 17.5 hours). In G1, there were higher proportions of females (69% vs. 35%, p<0.000), dialysis duration (88±61 months vs. 52±42, p<0.000), retransplantation (63% vs. 11%, p<0.000),PRA over 30% (54% vs. 6%, p<0.000), and number of transfusions (4.5±4 vs. 2±2, p<0.000). 

In G1, DSA types were distributed : class I 50%, class II 25%, and class I+II 25%.MFI titers for DSA I were 6393, DSA II 5234 y DSAI+DSAII 19158.Immunosuppression with Thymoglobulin were similar in both groups.The use of Gammaglobulin, Plasmapheresis, and Rituximab was significantly higher in G1 vs. G2 (86% vs. 8% p<0.000, 45% vs. 1.2% p<0.000, and 8% vs. 0.7% p<0.004, respectively).No differences were observed in incidence of DGF, but there was a difference in post-RT hospitalization (G1 26±17 days vs. G2 19±14 days, p<0.001). The incidence of AR was higher in G1 vs. G2 (29% vs. 13%, p<0.04). 

In positive DSA group,AR incidence was higher in DSA II vs. other DSAs (66.7% DSA II vs. 38.5% in DSA I+II vs. 7% in DSA I, p<0.000). Severe infection was higher in G1 vs. G2 (41% vs. 28%, p<0.04). Graft SV censored by death in G1 and G2 was 81% and 93% at 12 months and 62% and 80% at 60 months post-RT (p<0.000).Patient SV at 60 months was similar (G1 80% vs. G2 72%), with no differences between groups in the causes of death. Multivariate analysis revealed risk factors for AR: DGF (p<0.00, 95% CI (2.2-7.4)), DSA class II [p<0.000, 95% CI (3.4-20)], and having 4 incompatibilities in HLA A-B [p<0.03, 95% CI (1.01-4.8)]. Risk factors for renal graft loss censored by death were pre-existing DSA in RT [p<0.000, 95% CI (1.8-6.8)], donor >60 years [p<0.000, 95% CI 1.6-5.2)], and an episode of AR [p<0.017, 95% CI (1.1-

Patients DSA positive and negative XM crossmatch can receive RT with desensitization with acceptable medium-term results. Pre-existing DSAs are associated with lower 5-year renal graft survival and a higher risk of AR, especially with DSA class II.