title: Evaluation of Renal Allograft Biopsies for Graft Dysfunction and Relevance of C4d Staining in Antibody Mediated Rejection.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Associate Professor, Department of Pathology, M.S Ramaiah Medical College and Hospitals , MSRIT Post, MSRNagar, Bangalore, India .
authors.forename: Clement Wilfred
authors.initials: CW
authors.lastname: Devadass
authors.affiliation: ICMR Mentor and Guide, Professor & Head, Department of Pathology, Lab Medicine, Tranfusion Services & Immunohematology, Institute of Kidney Diseases and Research Centre & DR. H.L Trivedi Institute of Transplantation Sciences , B.J. Medical College & Civil Hospital Campus, Asarwa, Gujarat, India .
authors.forename: Aruna Vishwanth
authors.initials: AV
authors.lastname: Vanikar
authors.affiliation: Assistant Professor (Junior Nephropathologist), Department of Pathology, Lab Medicine, Tranfusion Services & Immunohematology, Institute of Kidney Diseases and Research Centre & DR. H.L Trivedi Institute of Transplantation Sciences , B.J. Medical College & Civil Hospital Campus, Asarwa, Gujarat, India .
authors.forename: Lovelesh Kumar
authors.initials: LK
authors.lastname: Nigam
authors.affiliation: Professor (Senior Nephropathologist), Department of Pathology, Lab Medicine, Tranfusion Services & Immunohematology, Institute of Kidney Diseases and Research Centre & DR. H.L Trivedi Institute of Transplantation Sciences , B.J. Medical College & Civil Hospital Campus, Asarwa, Gujarat, India .
authors.forename: Kamal Vinod
authors.initials: KV
authors.lastname: Kanodia
authors.affiliation: Professor (Senior Nephropathologist), Department of Pathology, Lab Medicine, Tranfusion Services & Immunohematology, Institute of Kidney Diseases and Research Centre & DR. H.L Trivedi Institute of Transplantation Sciences , B.J. Medical College & Civil Hospital Campus, Asarwa, Gujarat, India .
authors.forename: Rashmi Dalsukhbhai
authors.initials: RD
authors.lastname: Patel
authors.affiliation: PDCC Fellow, Department of Pathology, Lab Medicine, Tranfusion Services & Immunohematology, Institute of Kidney Diseases and Research Centre & DR. H.L Trivedi Institute of Transplantation Sciences , B.J. Medical College & Civil Hospital Campus, Asarwa, Gujarat, India .
authors.forename: Kyasakkala Sannaboraiah
authors.initials: KS
authors.lastname: Vinay
authors.affiliation: Professor, Department of Nephrology, Institute of Kidney Diseases and Research Centre & DR. H.L Trivedi Institute of Transplantation Sciences , B.J. Medical College & Civil Hospital Campus, Asarwa, Gujarat, India .
authors.forename: Himanshu V
authors.initials: HV
authors.lastname: Patel
keywords: CNI Toxicity; Peritubular capillary C4d deposition; Renal biopsy; Renal transplantation