Class II Alloantibody and Mortality in Simultaneous Liver-Kidney Transplantation

Abstract

Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver-kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for antibody-mediated kidney rejection. To further investigate the risk associated with donor-specific alloantibodies (DSA) in SLKT, we studied 86 consecutive SLKT patients with an available pre-SLKT serum sample. Serum samples were analyzed in a blinded fashion for HLA DSA using single antigen beads (median florescence intensity ≥ 2,000 = positive). Post-SLKT samples were analyzed when available (76%). Thirty patients had preformed DSA, and nine developed de novo DSA. Preformed class I DSA did not change the risk of rejection, patient or allograft survival. In contrast, preformed class II DSA was associated with a markedly increased risk of renal antibody mediated rejection (AMR) (p = 0.006), liver allograft rejection (p = 0.002), patient death (p = 0.02), liver allograft loss (p = 0.02) and renal allograft loss (p = 0.045). Multivariable modeling showed class II DSA (preformed or de novo) to be an independent predictor of patient death (HR = 2.2; p = 0.043) and liver allograft loss (HR = 2.2; p = 0.044). These data warrant reconsideration of the approach to DSA in SLKT.

Prevalence, Incidence and Risk Factors for Donor-Specific Anti-HLA Antibodies in Maintenance Liver Transplant Patients

“…In our study, persistent DSAs were more frequently anti-class-II DSAs (23/25 vs. 5/10, p < 0.0001). These data are consistent with previous studies (10,17), and may be explained by the ubiquitous expression of class-I DSAs on hepatocytes, which can lead to their rapid clearance (10).…”

“…The difference observed between Fontana et al's (15) study and ours is probably because we used a more sensitive assay. Recently, Miyagawa-Hayashino et al (16) assessed the prevalence of DSAs among stable pediatric LT patients who had survived for >5 years: they found a prevalence of 48% at 11 years (min-max: [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] posttransplantation. This high prevalence of DSAs is probably related to the very long follow-up in this Japanese study (16).…”

Incidence and impact of rejection following simultaneous liver-kidney transplantation

“…Finally, while all biopsies suggestive of antibody-mediated rejection stained positive for C4d and were re-confirmed as such by a renal transplant pathologist, we did not perform confirmatory donor specific antibody (DSA) testing until after 2007. As some of our SLK recipients developed antibody-mediated rejection and recently an association between class II DSA, liver/kidney rejection and graft survival was described [20], we now perform cross matches at the time of SLK and, if positive, monitor for DSA development. Since this protocol was initiated in 2010, we have had a number of SLK recipients with positive cross-matches and high titre DSA at SLK, who later developed antibody-mediated kidney rejection [21].…”

Impact of IgG3 Subclass and C1q-Fixing Donor-Specific HLA Alloantibodies on Rejection and Survival in Liver Transplantation

“…Historically, it has been recognized that the liver is relatively resistant to the pathologic effects of DSA compared to other solid organs (12)(13)(14)(15). However, with improved shortand long-term outcome in liver transplant recipients there has been a resurgence of interest in understanding the role of DSA in liver transplantation (16)(17)(18)(19)(20)(21)(22)(23)(24).…”