Transplant Glomerulopathy: Morphology, Associations and Mechanism

Abstract

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.

Long-term Results of Conversion From Calcineurin Inhibitors to Sirolimus in 150 Maintenance Kidney Transplant Patients

“…20 After kidney transplant, the occurrence of de novo proteinuria may be related to alloimmune processes, such as transplant glomerulopathy, which is associated with donor-specific alloantibodies. 21 In our study, 11 patients presented with donor-specific alloantibodies, but in those presenting with increased proteinuria during sirolimus therapy, only 8 had donor-specific alloantibodies. Therefore, other mechanisms may be involved in causing either de novo or worsening of proteinuria during sirolimus therapy.…”

Probabilistic (Bayesian) Modeling of Gene Expression in Transplant Glomerulopathy

“…26,[33][34][35][36] Finally, the development of TG and Cd4 expression has also been well characterized. 9,37,38 Thus, our preliminary data suggest that machine-learned Bayesian models may elucidate critical pathways related to the allograft pathology within transcriptional datasets.…”

Immune Responses to Tissue-Restricted Nonmajor Histocompatibility Complex Antigens in Allograft Rejection

“…Abs against angiotensin II type 1 (AT1) receptor [92] have been shown to increase the risk for refractory allograft rejection. Other non-HLA antigens that have been shown to play a role in kidney allograft rejection include perlecan, Col IV, Col VI, and the glomerular basement membrane protein, agrin [93, 94]. Recent studies have also suggested a role for antivimentin in the development of chronic renal rejection [95].…”

“…Recent studies have also suggested a role for antivimentin in the development of chronic renal rejection [95]. Transplant glomerulopathy (TG) is another form of renal allograft dysfunction that can affect over 20% of patients within 5 years of transplantation [93]. TG usually results from humoral injury to the endothelial cells [93], and both HLA and non-HLA Abs have been shown to play roles in its development.…”