Subclinical Rejection in Stable Positive Crossmatch Kidney Transplant Patients: Incidence and Correlations

Abstract

We reviewed 116 surveillance biopsies obtained approximately 1, 3, 6 and 12 months posttransplantation from 50 +XM live donor kidney transplant recipients to determine the frequency of subclinical cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). Subclinical CMR was present in 39.7% of the biopsies at 1 month and >20% at all other time points. The presence of diffuse C4d on biopsies obtained at each time interval ranged from 20 to 30%. In every case, where histological and immunohistological findings were diagnostic for AMR, donor-specific antibody was found in the blood, challenging the longheld belief that low-level antibody could evade detection due to absorption on the graft. Among clinical factors, only recipient age was associated with subclinical CMR. Clinical factors associated with subclinical AMR were recipient age, positive cytotoxic crossmatch prior to desensitization and two mismatches of HLA DR 51, 52 and 53 alleles. Surveillance biopsies during the first year post-transplantation for these high-risk patients uncover clinically occult processes and phenotypes, which without intervention diminish allograft survival and function.

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

“…Studies conducted in an era preceding DQ typing and antibody detection also found that HLA-DR compatibility, at the antigen level, carried the greatest influence on allograft outcomes (21,26). In a more recent study, two mismatches in HLA-DR51, -DR52 and -DR53 alleles conferred a greater risk of subclinical antibodymediated rejection among desensitization patients (62). Similarly, in re-transplant candidates greater DSA reactivity was observed in response to mismatches in HLA-DR53 followed by -DR51 and -DR52 and less so with HLA-DRB1 mismatches (37).…”

Antibody-Mediated Rejection in Cardiac Transplantation: Emerging Knowledge in Diagnosis and Management

“…6 Studies report that complement activation (C4d deposition) can be present in the absence of organ dysfunction in renal and cardiac allograft recipients, and thus, the term subclinical AMR has been introduced. 28,81,82 It is suggested that complement regulatory proteins can successfully terminate the complement cascade after activation in renal and heart allografts teleologically in an attempt to achieve a state of accommodation. 83 In some heart transplant recipients, complement deposition without allograft dysfunction represents accommodation.…”

Desensitization Protocols and Their Outcome

“…The Johns Hopkins group obtained surveillance biopsies in crossmatch-positive recipients at 1, 3, 6, and 12 months posttransplant (44,45). The frequency of subclinical cell-mediated rejection was 40% at 1 month and Ͼ20% at all other time points (44).…”