RAS Inhibition Attenuates Urine Angiotensin II-Regulated Proteins Associated with Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant Recipients.
1University Health Network, Toronto, ON, Canada
2Centre de Recherche du Centre Hospitalier de l'Université
de Montréal - CRCHUM, Montréal, QC, Canada
3Institute of Medical Science, University of Toronto, Toronto, ON, Canada
4Institute of Health Policy, University of Toronto, Toronto, ON, Canada
Meeting: 2017 American Transplant Congress
Abstract number: B22
Keywords: Fibrosis, Kidney transplantation, Proteinuria
Session Information
Session Name: Poster Session B: Acute and Chronic Rejection
Session Type: Poster Session
Date: Sunday, April 30, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Angiotensin-II (AngII), the main effector of the renin-angiotensin system (RAS), can lead to interstitial fibrosis/ tubular atrophy (IFTA) in kidney transplant recipients, mainly through AT-1R signalling. AT-1R signalling causes vascular rejection in the presence of activating AT-1R antibodies. Identification of kidney allograft recipients who will benefit from RAS blockade has been hampered by the lack of specific markers of activation of the kidney RAS. To address this gap in knowledge, we have defined AngII-regulated proteins and developed methods to quantify these proteins in urine. We next determined if a set of urinary markers that reflect kidney RAS activity correlate with RAS inhibition and IFTA in kidney allograft recipients.
Twenty patients from Canadian National Transplant Research Program, with urine and kidney biopsy samples archived before and after the initiation of RAS inhibition were selected. Another 20 patients with IFTA and 20 graft-age matched controls with concomitant urine and biopsy samples were selected. Mass spectrometry-based technique called Selected Reaction Monitoring (SRM) was used to quantify 6 AngII-regulated proteins in urine samples. Two-tailed paired and unpaired t-test was used to calculate the significance of urine protein excretion rate before and after initiation of RAS blockade and between IFTA and controls respectively.
We found significantly increased urine excretion rate of AngII-regulated proteins BST1, GLNA, LAMB2, LYPLA1, RHOB and TSP1 (p<0.05 for each) prior to initiation of RAS inhibition. The same proteins (except RHOB) were significantly increased (p<0.05) in urine of patients with IFTA compared to stable controls without IFTA.
Urine excretion rate of 6 AngII-regulated proteins reflects IFTA and kidney RAS activity. Mass spectrometry-based monitoring of these proteins may improve early detection of IFTA and may be used to guide therapy with RAS inhibitors. AngII-regulated proteins may also be informative in identification of vascular rejection mediated by AT-1R antibodies.
CITATION INFORMATION: Mohammed-Ali Z, Reid S, Yip P, Cardinal H, Hébert M.-J, Li Y, Kim S, Konvalinka A. RAS Inhibition Attenuates Urine Angiotensin II-Regulated Proteins Associated with Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Mohammed-Ali Z, Reid S, Yip P, Cardinal H, Hébert M-J, Li Y, Kim S, Konvalinka A. RAS Inhibition Attenuates Urine Angiotensin II-Regulated Proteins Associated with Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant Recipients. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/ras-inhibition-attenuates-urine-angiotensin-ii-regulated-proteins-associated-with-interstitial-fibrosis-and-tubular-atrophy-in-kidney-transplant-recipients/. Accessed May 25, 2025.« Back to 2017 American Transplant Congress