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Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts.
J Am Soc Nephrol. 2015 Jul; 26(7):1721-31.JA

Abstract

Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria.

Authors+Show Affiliations

Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Paris Descartes University and Hôpital Necker, alexandreloupy@gmail.com.Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Methodology Unit (EA 3181), CHRU de Besançon, France;Paris Descartes University and Hôpital Necker.Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France;Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Department of Pathology, Necker Hospital, Paris, France; and.Department of Pathology, Necker Hospital, Paris, France; and.Department of Pathology, Saint Louis Hospital, Paris, France.Hôpital Européen Pompidou, and.Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France;Paris Descartes University and Hôpital Necker.Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France;Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France;Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Paris Descartes University and Hôpital Necker.Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France;

Pub Type(s)

Comparative Study
Journal Article
Observational Study

Language

eng

PubMed ID

25556173

Citation

Loupy, Alexandre, et al. "Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts." Journal of the American Society of Nephrology : JASN, vol. 26, no. 7, 2015, pp. 1721-31.
Loupy A, Vernerey D, Tinel C, et al. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts. J Am Soc Nephrol. 2015;26(7):1721-31.
Loupy, A., Vernerey, D., Tinel, C., Aubert, O., Duong van Huyen, J. P., Rabant, M., Verine, J., Nochy, D., Empana, J. P., Martinez, F., Glotz, D., Jouven, X., Legendre, C., & Lefaucheur, C. (2015). Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts. Journal of the American Society of Nephrology : JASN, 26(7), 1721-31. https://doi.org/10.1681/ASN.2014040399
Loupy A, et al. Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts. J Am Soc Nephrol. 2015;26(7):1721-31. PubMed PMID: 25556173.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts. AU - Loupy,Alexandre, AU - Vernerey,Dewi, AU - Tinel,Claire, AU - Aubert,Olivier, AU - Duong van Huyen,Jean-Paul, AU - Rabant,Marion, AU - Verine,Jérôme, AU - Nochy,Dominique, AU - Empana,Jean-Philippe, AU - Martinez,Frank, AU - Glotz,Denis, AU - Jouven,Xavier, AU - Legendre,Christophe, AU - Lefaucheur,Carmen, Y1 - 2015/01/02/ PY - 2014/04/23/received PY - 2014/10/03/accepted PY - 2015/1/4/entrez PY - 2015/1/4/pubmed PY - 2015/9/12/medline KW - allograft function KW - allograft loss KW - renal medicine KW - translational research KW - transplant rejection SP - 1721 EP - 31 JF - Journal of the American Society of Nephrology : JASN JO - J. Am. Soc. Nephrol. VL - 26 IS - 7 N2 - Kidney allograft rejection can occur in clinically stable patients, but long-term significance is unknown. We determined whether early recognition of subclinical rejection has long-term consequences for kidney allograft survival in an observational prospective cohort study of 1307 consecutive nonselected patients who underwent ABO-compatible, complement-dependent cytotoxicity-negative crossmatch kidney transplantation in Paris (2000-2010). Participants underwent prospective screening biopsies at 1 year post-transplant, with concurrent evaluations of graft complement deposition and circulating anti-HLA antibodies. The main analysis included 1001 patients. Three distinct groups of patients were identified at the 1-year screening: 727 (73%) patients without rejection, 132 (13%) patients with subclinical T cell-mediated rejection (TCMR), and 142 (14%) patients with subclinical antibody-mediated rejection (ABMR). Patients with subclinical ABMR had the poorest graft survival at 8 years post-transplant (56%) compared with subclinical TCMR (88%) and nonrejection (90%) groups (P<0.001). In a multivariate Cox model, subclinical ABMR at 1 year was independently associated with a 3.5-fold increase in graft loss (95% confidence interval, 2.1 to 5.7) along with eGFR and proteinuria (P<0.001). Subclinical ABMR was associated with more rapid progression to transplant glomerulopathy. Of patients with subclinical TCMR at 1 year, only those who further developed de novo donor-specific antibodies and transplant glomerulopathy showed higher risk of graft loss compared with patients without rejection. Our findings suggest that subclinical TCMR and subclinical ABMR have distinct effects on long-term graft loss. Subclinical ABMR detected at the 1-year screening biopsy carries a prognostic value independent of initial donor-specific antibody status, previous immunologic events, current eGFR, and proteinuria. SN - 1533-3450 UR - https://www.unboundmedicine.com/medline/citation/25556173/Subclinical_Rejection_Phenotypes_at_1_Year_Post_Transplant_and_Outcome_of_Kidney_Allografts_ L2 - http://jasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=25556173 DB - PRIME DP - Unbound Medicine ER -