Endothelial-to-Myofibroblast Transition (en-mt) and Low Expression of Capillary Vegf Enhance the Development of Interstitial Fibrosis and Glomerulosclerosis Induced by Microvascular Destruction in Antibody-Mediated Rejection (abmr) Patients
1Department of Pathology, Baskent University, Ankara, Turkey, 2Division of Transplantation, Department of General Surgery, Baskent University, Ankara, Turkey
Meeting: 2021 American Transplant Congress
Abstract number: 451
Keywords: Angiography, Graft failure
Topic: Clinical Science » Kidney » Kidney Complications: Immune Mediated Late Graft Failure
Session Information
Session Name: Kidney Alloimmune Responses
Session Type: Poster Video Chat
Date: Monday, June 7, 2021
Session Time: 7:30pm-8:30pm
Presentation Time: 7:40pm-7:50pm
Location: Virtual
*Purpose: Interstitial fibrosis (IF) and glomerulosclerosis (GS) are the most important cause of graft loss. Although the rate of microvascular destruction (MVD) is similar in recipients with ABMR, some develop higher IF and GS during follow-up. The exact mechanism of this process is unknown. We aimed to understand why some patients compared to others show higher rates of IF and GS, although they have similar MVD due to ABMR.
*Methods: A total of 102 patients with ABMR studied. Biopsies highlighted with CD31 and HLA-DR to determine the mean number of glomerular capillaries (GCs) and peritubular capillaries (PTCs). VEGF expression of GCs and PTCs examined. Capillary expression of α-SMA and F-actin was studied to show the development of En-MT. Follow-up biopsies analyzed for the development of IF and GS.
*Results: The mean capillary numbers were 43,4±11,8 and 30,3±8,7 for GCs and PTCs, respectively. The number of PTCs correlated significantly with PTC inflammation (r= -0,56, P<.001), PTC-VEGF expression (r=0,41, P<0,001), En-MT (r= -0,45, P<0.001), proteinuria (r= -0,34, P=.001), the development of IF (r= -0,56, P<0.001), and graft loss (r= -0,57, P<.001). The glomerular capillary loss was also significantly associated with GC inflammation (r= -0,64, P<.001), GC-VEGF expression (r=0,89, P<.001), En-MT (r= -0,61, P<.001), proteinuria (r= -0,89, P<.001), the development of GS (r= -0,70, P<.001), and graft loss (r= -0,44, P<.001). The incidence of proteinuria, the development of IF, the development of GS, and graft loss increased with decreasing PTC and GC VEGF expression and increasing En-MT ratio (p<.001). Although the mean number of PTCs and GCs in some cases was higher than the cutoff point, it was observed that patients with high En-MT and low capillary VEGF expression showed a higher incidence of IF and GS development and, as a result, increased graft loss.
*Conclusions: Our findings indicate that monitoring PTC and GC numbers with the presence or absence of En-MT and capillary VEGF expression may become a valuable predictive marker for graft loss. The preservation of capillary endothelium by higher capillary VEGF and lower En-MT can play an essential role in preserving graft survival. Thus the usage of angiogenic factors may become a new approach in the treatment of renal transplantation.
To cite this abstract in AMA style:
Ozdemir B, Akcay E, Atilgan AOk, Haberal M. Endothelial-to-Myofibroblast Transition (en-mt) and Low Expression of Capillary Vegf Enhance the Development of Interstitial Fibrosis and Glomerulosclerosis Induced by Microvascular Destruction in Antibody-Mediated Rejection (abmr) Patients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/endothelial-to-myofibroblast-transition-en-mt-and-low-expression-of-capillary-vegf-enhance-the-development-of-interstitial-fibrosis-and-glomerulosclerosis-induced-by-microvascular-destruction-in-ant/. Accessed May 6, 2025.« Back to 2021 American Transplant Congress