Format

Send to

Choose Destination
J Am Soc Nephrol. 2015 Jul;26(7):1721-31. doi: 10.1681/ASN.2014040399. Epub 2015 Jan 2.

Subclinical Rejection Phenotypes at 1 Year Post-Transplant and Outcome of Kidney Allografts.

Author information

1
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.
2
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;
3
Paris Descartes University and Hôpital Necker.
4
Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France;
5
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.
6
Department of Pathology, Necker Hospital, Paris, France; and.
7
Department of Pathology, Saint Louis Hospital, Paris, France.
8
Hôpital Européen Pompidou, and.
9
Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, Paris, France;
10
Paris Translational Research Center for Organ Transplantation, National Institute of Health and Medical Research, UMR-S970, Paris, France; Paris Descartes University and Hôpital Necker.

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.

KEYWORDS:

allograft function; allograft loss; renal medicine; translational research; transplant rejection

PMID:
25556173
PMCID:
PMC4483584
DOI:
10.1681/ASN.2014040399
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center