Introduction. Pre-transplant DSAII is associated with chronic antibody mediated rejection/transplant glomerulopathy (TG) and high risk of graft loss (GL). However, not all DSAII result in TG and/or GL. The goal of this study was to search for factors that identify early, progressive DSAII injury that may be amenable to therapy.
Methods. Included were 1153 crossmatch negative, adult recipients, transplanted from 1998-2010 with 1-year protocol biopsies. Patients with recurrent disease were excluded. Age, 52±14, 75% living donors, follow up 76±39 months. 77% received thymoglobulin induction and 87% triple immunosuppression with tacrolimus.
Results. 19.8% of recipients had DSAII pre-transplant. At 1 year compared to DSAII-, DSAII+ recipients did not differ in graft function, blood pressure or proteinuria. However, the incidence of biopsy-proven TG was higher in DSAII+ than in DSAII- recipients (9.3% vs 2.2%, p<0.0001). DSAII related to GL. Thus, 5 and 10 year GL were 3.7 and 13.2% in DSAII- and 14.3 and 26.8% in DSAII+ recipients (HR=2.52 (1.44-4.39), p=0.001) independently of recipient age, acute rejection, graft function and proteinuria. The DSAII/GL relationship was modified by TG and by proteinuria. Thus, TG at 1 year was associated with very high risk of GL (HR=15.2, p<0.0001) but in DSAII+/TG- patients the DSAII/GL relationship was variable and statistically not significant (HR=1.76 (0.85-3.63), p=0.127). Similarly, in DSAII+ patients only those with proteinuria, even at low levels (>150-500 mg/day), were at risk of GL (HR=4.93 (2.47-9.83), p<0.0001) while in the absence of proteinuria DSAII did not related to GL (p=0.166). Furthermore, among DSAII+/TG- patients proteinuria identified a subgroup at high risk of GL (HR=2.78, p=0.020). Proteinuria related to glomerulitis and had a weak correlation with podocyte foot process fusion (p=0.071) but it did not relate to capillary endothelial cell reactive changes (electron microscopy in TG-, N=47).
Conclusions. In DSAII+ recipients, TG and/or low level proteinuria are early signs of a graft in trouble. Conversely, absence of proteinuria, even with DSAII+, suggests very low risk of graft loss. Early identification of DSAII+ patients at high risk of GL will help to target interventions to ameliorate chronic antibody mediated injury.
To cite this abstract in AMA style:Rodrigo E, Cornell L, Chopra B, Amer H, Dean P, Stegall M, Cosio F. Early Indicators of Kidney Graft Injury Mediated by Class II Donor Specific Antibodies (DSAII) [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/early-indicators-of-kidney-graft-injury-mediated-by-class-ii-donor-specific-antibodies-dsaii/. Accessed June 20, 2021.
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