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

Abstract

C4d deposition in peritubular capillaries is a specific marker for the presence of antidonor antibodies in renal transplant recipients and is usually associated with antibody-mediated rejection (AMR) in conventional allografts. In ABO-incompatible grafts, however, peritubular capillary C4d is often present on protocol biopsies lacking histologic features of AMR; the significance of C4d in this setting remains unclear. For addressing this, data from 33 patients who received ABO-incompatible renal allografts (after desensitization) were retrospectively reviewed. Protocol biopsies were performed at 1 and/or 3 and 6 mo after transplantation in each recipient and at 12 mo in 28 recipients. Twenty-one patients (group A) had strong, diffuse peritubular capillary C4d staining without histologic evidence of AMR or cellular rejection on their initial protocol biopsies. The remaining 12 patients (group B) had negative or weak, focal peritubular capillary C4d staining. Three grafts (two in group B) were lost but not as a result of AMR. Excluding these three patients, serum creatinine levels were similar in the two groups at 6 and 12 mo after transplantation and at last follow-up; however, recipients in group A developed significantly fewer overall chronic changes, as scored by the sum of Banff chronic indices, than group B during the first year after transplantation. These results suggest that diffuse peritubular capillary C4d deposition without rejection is associated with a lower risk for scarring in ABO-incompatible renal allografts; the generalizability of these results to conventional allografts remains unknown.

Glomerular damage as a predictor of renal allograft loss

“…This finding agrees with recently published studies (25)(26)(27)(28)(29). Wavamunno et al (30) showed that endothelial and subendothelial ultrastructural abnormalities in glomerular and peritubular capillaries are sensitive early markers of CTG.…”

Incidence and Outcomes of BK Virus Allograft Nephropathy among ABO- and HLA-Incompatible Kidney Transplant Recipients

“…One possibility is an interaction between BK virus and the immune system, which occurs at many different levels (21) and may be altered in the milieu of blood group incompatibility. The occurrence of a graft accommodation phenotype, an acquired resistance of an organ to immune-mediated damage, is more frequently observed in ABO-incompatible kidney recipients than in HLAincompatible recipients (22)(23)(24)(25). The results of this study suggest that ABO-incompatible kidney recipients who do not develop the accommodation phenotype are more likely to develop BKVAN than are HLA-incompatible and ABOcompatible patients.…”

Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

“…A European study including protocol biopsy samples from early and late time points found no reduction in allograft survival in C4d ϩ versus C4d Ϫ biopsy samples. 13 Recently, a study by Haas et al 26 of ABO-incompatible renal allografts showed that diffuse PTC C4d deposition without histologic evidence of AMR or cellular rejection in their initial protocol biopsies was associated with a lower risk for scarring at 1 yr. Several factors may explain the conflicting conclusions in these studies, including limitations as a result of highly selected patient groups, 12 short follow-up, 24 -26 and the inclusion of both early and late allograft biopsies. 13,22,23,25 In this study, we identified a unique cohort of renal transplant recipients with allografts surviving Ն10 yr after transplantation with biopsies performed for evaluation of graft dysfunction with or without proteinuria at these later time points.…”