Transplant glomerulopathy: morphology, associations and mechanism.
Transplant glomerulopathy (TG) is a lesion with specific morphology and strong evidence of an immune mechanism. The incidence of TG is approximately 20% by 5 years after transplantation. TG is characterized by proteinuria, hypertension and declining graft function. Appearances on light microscopy include thickened capillary walls and double contours, with reduplication or lamination of the glomerular basement membrane on electron microscopy. TG is associated with acute rejection, the antibody status before transplantation and de novo HLA antibodies. HLA class II and/or donor-specific antibodies incur additional risks. Desensitization protocols do not always prevent the development of TG in highly sensitized individuals. Associations between TG, past or current C4d and the presence of alloantibodies are recognised, however, C4d in the peri-tubular capillaries or glomeruli is not a prerequisite at the time of diagnosis. Clinical observation and animal models suggest that TG arises as a consequence of chronic endothelial cell (EC) injury by the humoral arm of the immune system. In some cases, this follows a period of EC accommodation after an episode of acute injury. Proposed treatments include augmentation of background immunosuppression, and trials of monoclonal therapies targeted at CD20-positive B cells are underway.
Fotheringham
James
J
Sheffield Kidney Institute, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. james.fotheringham@nhs.net
Angel
Carole A
CA
McKane
William
W
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015935:Complement C4b / Q000276:immunology; D003171:Complement Pathway, Classical; D004730:Endothelium, Vascular / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007518:Isoantibodies / Q000276:immunology; D007674:Kidney Diseases / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007678:Kidney Glomerulus / Q000098:blood supply / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008252:Macaca fascicularis; D018448:Models, Immunological; D010446:Peptide Fragments / Q000276:immunology; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011917:Rats, Inbred Lew
D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d