Analysis of Renal Transplant Protocol Biopsies in ABO-Incompatible Kidney Transplantation

Abstract

All contributing authors have declared that there is no relationship with any companies and no conflict of interest in this study.Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance.

Banff 2013 Meeting Report: Inclusion of C4d-Negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions

“…An elastic stain may be helpful as absence of elastic lamellae is more typical of chronic rejection and multiple elastic lamellae are most typical of arteriosclerosis, although these findings are not definitive. 11 The clinical significance of these findings may be quite different in grafts exposed to anti-blood-group antibodies (ABO-incompatible allografts), where they do not appear to be injurious to the graft (18,19) and may represent accommodation. However, with anti-HLA antibodies such lesions may progress to chronic ABMR (20) and more outcome data are needed.…”

C4d Deposition without Rejection Correlates with Reduced Early Scarring in ABO-Incompatible Renal Allografts

“…In the absence of early T cell help (possibly prevented by multidrug immunosuppressive therapy), antibodies produced against a carbohydrate antigen structurally similar to human blood group antigens in a mouse heart xenograft model result in graft accommodation, with these antibodies binding to the carbohydrate antigen on the graft but not producing AMR. 29,30 Still, in this model, AMR did occur when antibodies to the same carbohydrate antigen were produced in the setting of early T cell help, 29 and AMR (both clinical and subclinical) does occur in some ABO-incompatible renal allografts, [12][13][14]16,31,32 including four (12%) of 33 in this study. Conversely, a small number of ABO-compatible, positive cross-match (HLA-incompatible) grafts showed C4d staining on protocol biopsies without histologic changes of AMR or subsequent development of graft dysfunction or scarring, including TG.…”

“…11 By contrast, we and others have noted that the majority of protocol biopsies of ABO-incompatible grafts show PTC C4d deposition that is often diffuse but only infrequently associated with histologic changes of AMR. [12][13][14] The significance of C4d staining in the absence of these histologic changes remains unclear. 15 In this study, we retrospectively examined renal allograft biopsies and clinical data from 33 patients who received an ABO-incompatible renal allograft after desensitization to remove blood group antibodies (BGA).…”

A Case of Desensitization, Transplantation, and Allograft Dysfunction

“…Second, in the setting of ABO-incompatible transplantation, the presence of C4d alone does not imply rejection. Its presence has been well described in the setting of stable/good allograft function and in the absence of light microscopic changes of AMR (18). The reasons why C4d positivity is poorly correlated with "true" AMR in ABO-incompatible, as opposed to HLA-incompatible, renal transplantation are not clear.…”