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Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection.
PLoS One. 2013; 8(5):e64994.Plos

Abstract

The Endothelial Protein C Receptor (EPCR) is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR) and antibody-mediated (ABMR) rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR), we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation.

Authors+Show Affiliations

Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. l.c.lattenist@amc.uva.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23717683

Citation

Lattenist, Lionel, et al. "Renal and Urinary Levels of Endothelial Protein C Receptor Correlate With Acute Renal Allograft Rejection." PloS One, vol. 8, no. 5, 2013, pp. e64994.
Lattenist L, Kers J, Claessen N, et al. Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection. PLoS ONE. 2013;8(5):e64994.
Lattenist, L., Kers, J., Claessen, N., ten Berge, I. J., Bemelman, F. J., Florquin, S., & Roelofs, J. J. (2013). Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection. PloS One, 8(5), e64994. https://doi.org/10.1371/journal.pone.0064994
Lattenist L, et al. Renal and Urinary Levels of Endothelial Protein C Receptor Correlate With Acute Renal Allograft Rejection. PLoS ONE. 2013;8(5):e64994. PubMed PMID: 23717683.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renal and urinary levels of endothelial protein C receptor correlate with acute renal allograft rejection. AU - Lattenist,Lionel, AU - Kers,Jesper, AU - Claessen,Nike, AU - ten Berge,Ineke J M, AU - Bemelman,Frederike J, AU - Florquin,Sandrine, AU - Roelofs,Joris J T H, Y1 - 2013/05/22/ PY - 2012/08/27/received PY - 2013/04/21/accepted PY - 2013/5/30/entrez PY - 2013/5/30/pubmed PY - 2014/1/3/medline SP - e64994 EP - e64994 JF - PloS one JO - PLoS ONE VL - 8 IS - 5 N2 - The Endothelial Protein C Receptor (EPCR) is expressed on leukocytes, on endothelium of large blood vessels and to a lesser extent on capillaries. Membrane bound EPCR plays an important role in the activation of protein C which has anticoagulant, anti-inflammatory and cytoprotective effects. After cleavage by a protease EPCR is also found as a soluble protein. Acute rejection of kidney allografts can be divided in T-cell-mediated rejection (TCMR) and antibody-mediated (ABMR) rejection. The latter is characterized by strong activation of coagulation. Currently no reliable non-invasive biomarkers are available to monitor rejection. Renal biopsies were available from 81 renal transplant patients (33 without rejection, 26 TCMR and 22 ABMR), we had access to mRNA material, matched plasma and urine samples for a portion of this cohort. Renal EPCR expression was assessed by RT-PCR and immunostaining. Plasma and urine sEPCR levels were measured by ELISA. ABMR patients showed higher levels of EPCR mRNA than TCMR patients. EPCR expression on glomeruli was significantly elevated in ABMR patients than in TCMR or control patients. In the peritubular capillaries EPCR expression was higher in ABMR patients than in control patients. EPCR expression was higher in tubules and arteries of rejection patients than in control patients. Plasma sEPCR levels did not differ. Urine sEPCR levels were more elevated in the ABMR group than in patients with TCMR or without rejection. ROC analysis demonstrated that urinary sEPCR is appropriate to discriminate between ABMR patients and TCMR or control patients. We conclude that urinary sEPCR could be a novel non-invasive biomarker of antibody mediated rejection in renal transplantation. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23717683/Renal_and_urinary_levels_of_endothelial_protein_C_receptor_correlate_with_acute_renal_allograft_rejection_ L2 - http://dx.plos.org/10.1371/journal.pone.0064994 DB - PRIME DP - Unbound Medicine ER -