Aims: Chronic-active antibody mediated rejection (c-aABMR) is a major cause of kidney graft loss. Currently, little is known about the relation between histopathologic parameters and renal... Show moreAims: Chronic-active antibody mediated rejection (c-aABMR) is a major cause of kidney graft loss. Currently, little is known about the relation between histopathologic parameters and renal allograft survival.Methods and results: Between 2008 and 2014, 41 patients with a progressive decrease in renal function were diagnosed with c-aABMR according to Banff 2015 and followed up for at least 3 years. Clinical and renal biopsy characteristics were analyzed for association with graft survival.During follow-up 26 cases lost their graft because of c-aABMR at a median follow up of 40 months after diagnosis.Cases with v-lesions in their biopsy had a significant higher loss of eGFR prior to diagnosis. The total inflammation score (r = -0.45 p = .007) and the severity of interstitial fibrosis (r = -0.38 p = .023) were related to the eGFR at time of biopsy.Univariate regression analysis showed that eGFR at time of biopsy, total inflammation, interstitial fibrosis and the sum chronicity score were significantly related to the risk for graft failure during follow-up. In a multivariate analysis only the severity of interstitial fibrosis remained associated with decreased graft survival (HR 1.9 per score point, 95% CI 1.2-2.8, p = .004).Conclusion: Severity of renal interstitial fibrosis and not inflammation predicts graft survival in cases of c-aABMR. Show less
Kort, H. de; Willicombe, M.; Brookes, P.; Dominy, K.M.; Santos-Nunez, E.; Galliford, J.W.; ... ; Roufosse, C. 2013
In this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR... Show moreIn this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR) after transplantation and on a potential strategy using cellular immune modulation to prevent acute rejection. First, we retrospectively evaluated the relevance of diffuse C4d-positive peritubular capillary staining in a well-defined kidney transplantation cohort with proven early acute rejections (Chapter 2). Second, the negative impact of AMR on pancreas graft survival was investigated, which proved to be significant (Chapter 3). We subsequently analyzed all SPKT patients at the LUMC with early pancreas graft loss to examine the role of AMR due to presumed thrombosis and/or acute rejection (Chapter 4). In Chapter 5, a clinical update is presented on islets of Langerhans transplantation, focusing on the alternative _-cell replacement therapy that is currently employed in the LUMC (Chapter 5). Furthermore, we reviewed the role of both lymphatic- and blood-vessel vascularization and the role of neuronal reconnection after islet transplantation with data from our own rat islet transplantation models (Chapter 6). Finally, in a rodent allogeneic islet transplantation model, we attempted to induce tolerance by using donor-derived, dexamethasone-pretreated dendritic cells (Chapter 7). Show less
