Evaluation of Renal Allograft Biopsies for Graft Dysfunction and Relevance of C4d Staining in Antibody Mediated Rejection

Abstract

Introduction: Biopsy remains gold standard for diagnosis of Graft Dysfunction (GD). It guides clinical management, provides valuable insights into pathogenesis of early and late allograft injury and is indispensable for distinguishing rejection from non- rejection causes of GD.

Aim: The primary aim of the study was to evaluate the diverse histomorphological lesions in renal allograft biopsy (RAB). Further, we determined the frequency of peritubular capillary (PTC) C4d positivity and its correlation with microvascular inflammation in Antibody Mediated Rejection (AMR).

Materials and methods: This was a prospective study on RAB over a period of 2 months. Histopathological evaluation was undertaken as per revised Banff'13 schema. Immunohistochemistry was performed to detect PTC C4d deposition.

Results: Sixty five diagnostic biopsies were evaluated. Mean patient age was 34 years and males were predominant. The time interval between graft biopsy and transplantation ranged from 5 days to 8 years, with 52.3% biopsies belonging to period of ≤ 6 months post-transplant. Immune injuries were observed in 40 biopsies out of which AMR was observed in 35 biopsies. Calcineurin inhibitor toxicity (CNI Toxicity) was the second commonest cause observed in 12 biopsies and other lesions including de novo glomerulopathies were observed in the remaining biopsies. The sensitivity of C4d in detecting acute AMR was 55% and chronic AMR was 23.5.

Conclusion: AMR and CNI Toxicity account for majority of graft dysfunction. C4d is not as sensitive a marker of AMR, as was initially thought. Higher proportion of moderate microvascular inflammation is found in diffuse C4d positive cases compared to focal C4d positive cases.

Keywords: CNI Toxicity; Peritubular capillary C4d deposition; Renal biopsy; Renal transplantation.

[Table/Fig-1]:

Timing of allograft biopsies post transplantation. x axis indicates time of biopsy, y indicates No. of cases..

[Table/Fig-3]:

Types of rejection with or without superimposed non-rejection causes. ABMR- Antibody mediated rejection, Others- non-rejection causes, TCMR- T-cell-mediated rejection. The 2 cases of borderline rejection were amenable to steroid therapy and hence were considered to be earliest evidence of immunological activity.

[Table/Fig-8]:

(A) AMR with moderate transplant glomerulitis (long arrow) and moderate peritubular capillaritis (short arrow) PAS X 200. (B) C4d immunohistochemistry with diffuse peritubular capillary deposits of C4d (Score: C4d3) (arrow) X200.