Best practice: gross examination and sampling of surgical specimens from the urinary bladder.

This review examines aspects of handling biopsies and surgical specimens from the urinary bladder with the aim of providing guidance to ensure that the pathologist is fully able to inform clinicians of all relevant factors that might have bearing on management or prognosis. It also offers recommendations on good practice in reporting in the setting of the specialist multidisciplinary meeting and emphasises quality control of the process, referring to recently published guidelines and consensuses while admitting that many of the recommendations may not be supported by a strong evidence base. The role of urine cytology and the value of frozen sections in urological practice are discussed. Participation in regular clinical audit and the national urological pathology External Quality Assurance (EQA) are recommended.

Association between C4d staining in renal transplant biopsies, production of donor-specific HLA antibodies, and graft outcome.

BACKGROUND: We carried out a retrospective study of C4d staining in paraffin sections from renal transplant biopsies to determine the association between C4d staining, donor-specific antibodies (DSA), histological features, and graft outcome. METHODS: We studied 92 patients who had been biopsied for graft dysfunction. Biopsies were classified using Banff 97 criteria and features suggestive of antibody-mediated rejection were noted. Paraffin sections were stained with a polyclonal antibody using an immunoperoxidase technique. The presence of DSA in concurrent sera was determined by enzyme-linked immunosorbent assay and clinical data were reviewed. RESULTS: Of the 92 cases, 15% showed diffuse and 24% showed focal C4d positivity. The grafts failed in 36% of the diffuse (P<0.025), 23% of the focal, and 7% of the negative group at between one month and 15 years posttransplantation. Only patients in the group with diffuse C4d positivity had concurrent DSA (five cases, P<0.001). Of the five DSA-positive patients, three had type II acute rejection and two of these transplants subsequently failed. The remaining two had chronic allograft nephropathy with features of alloimmune injury. Only two of the nine DSA-negative/C4d-positive transplants had failed at the time of writing, in one case due to recurrent disease. CONCLUSION: We demonstrated a significant association between diffuse C4d staining, production of DSA, and graft failure. Although the concurrent detection of DSA and C4d positivity is uncommon in our patients, these results indicate that outcome in this group is poor and they may benefit from therapies directed at the humoral response.

The role of HLA-specific antibodies in kidney transplant rejection: published studies and local data.

The post-transplantation production of antibodies directed against donor HLA class I and class II mismatches has been shown to be associated with transplant rejection. Recipient sensitization against donor HLA plays a key role in transplant rejection; this risk is best minimized by efficient pre-transplant antibody detection and definition, effective pre-allocation cross-matching, and minimization of HLA mismatches between donor and recipient. The term "PRA" is of little value. Identification of the HLA specificity to which an antibody is directed is essential and now possible using contemporary methodology. It is now recognized that antibody-mediated rejection should be diagnosed on the basis of allograft dysfunction, characteristic features of histology, C4d immunohistology, and the presence of donor-specific antibodies. HLA-DP is becoming recognized as a "transplantation antigen." For the future, the repertoire of a histocompatibility laboratory must expand to include typing organ transplant recipients and donors for HLA-DP and also the definition of antibodies to DP. Antibodies to non-HLA targets should be an important consideration when assessing factors that influence transplant outcome.