Anti-Angiotensin II Type 1 Receptor Antibodies and Kidney Transplant Outcomes

NCT03466775 | Completed

• 1 other identifier: AT1R001
• Study Type: observational
• Target: 1,845
• Locations: 1 country
• Sites: 2

Brief Summary

Incompatibility between non-genetically identical donors and recipients has been increasingly recognized as the main contributing factor to solid allograft rejection and failure, through the triggering of donor-specific responses mediated by T- and B-lymphocytes. The Human Leucocyte Antigen (HLA) system has been identified as the main target of donor-specific responses, especially through the production by the recipient of antibodies directed toward non-self donor HLA molecules expressed on the allograft endothelium. As a consequence, in organ transplantation, the current approach to immunological risk stratification, patient monitoring and rejection diagnosis is based on biomarkers derived from the HLA system. However, this approach does not provide a sufficient accuracy for the risk stratification and the diagnosis of immunological complications in solid organ transplantation, which still remain the dominant cause of allograft failure. A recent body of evidence supports that specific non-HLA antigens expressed on the allograft endothelium may be relevant to allograft rejection, suggesting that a new strategy to transplant diagnostic testing at a non-HLA level would help to overcome the limitations of the current HLA-based approach to immunological assessment of transplant recipients. Among antibodies to non-HLA endothelial antigens, angiotensin II type 1 receptor activating antibodies have been the most widely reported antibodies to associate with the occurrence of allograft rejection, dysfunction and loss, even if their independent role, with respect to the presence of concomitant anti-HLA antibodies, has not been demonstrated.

Conditions

Kidney Transplant Failure and Rejection

Keywords

Kidney transplantation; Allograft rejection; Allograft survival; Anti-angiotensin II type 1 receptor antibody

Outcome Measures

Primary Outcomes (3)

• Incidence of biopsy-proven kidney allograft rejection according to the presence of post-transplant circulating anti-angiotensin II type 1 receptor antibodies within the first year after transplantation

  Anti-angiotensin II type 1 receptor antibody positivity is defined by serum concentration \>10 U/mL using quantitative ELISA. Stratified analysis is performed according to the presence of post-transplant concomitant circulating donor-specific anti-HLA antibodies detected by single antigen bead assay in serum. Allograft rejection is defined on the basis of the 2015 update of the Banff classification for allograft rejection.

  One year after transplantation

• Comparison of allograft injury phenotype according to post-transplant anti-angiotensin II type 1 receptor antibody status and concomitant donor-specific anti-HLA antibody status

  Injury phenotype is based on histological allograft elementary lesions defined by the Banff classification (glomerulitis, peritubular capillaritis, interstitial inflammation, tubulitis, endarteritis, chronic allograft glomerulopathy, interstitial fibrosis, tubular atrophy, arteriosclerosis, arteriolar hyalinosis, C4d deposition in peritubular capillaries).

  One year after transplantation

• Association between the presence of post-transplant circulating anti-angiotensin II type 1 receptor antibodies and time to kidney allograft

  Univariate and multivariable models are performed, including adjustment for recipient age and gender, biopsy indication, glomerular filtration rate, proteinuria, presence of post-transplant circulating donor-specific anti-HLA antibodies and histological elementary lesions defined by the Banff classification, assessed at the time of antibody detection.

  Up to seven years after inclusion

Secondary Outcomes (2)

• Incidence of anti-angiotensin II Type 1 receptor antibodies in kidney transplant recipients within the first year after transplantation

  One year after transplantation

• Comparison of endothelial-associated transcript expression (ENDAT) levels according to anti-angiotensin II type 1 receptor antibody status and donor-specific anti-HLA antibody status

  One year after transplantation

Interventions

Anti-angiotensin II type 1 receptor antibody measurement DIAGNOSTIC_TEST

Anti-angiotensin II type 1 receptor antibodies are assessed using quantitative ELISA in stored serum samples obtained within the first year after transplantation

Measurement of ENDAT expression level allograft DIAGNOSTIC_TEST

Endothelial-associated transcript expression level is assessed using microarray in stored kidney allograft biopsies obtained within the first year after transplantation

Allograft survival OTHER

Allograft rejection appearance OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population includes kidney recipients undergoing transplantation between January 1, 2008 and December 31, 2012 at Necker and Saint-Louis Hospitals (Paris, France).

You may qualify if:

• Kidney recipient transplanted between January 1, 2008 and December 31, 2012
• Kidney recipient over 18 years of age
• Simultaneous histological and serological assessment within the first year after transplantation, including i) kidney allograft biopsy, ii) assessment of donor-specific anti-HLA antibodies, and available stored serum for anti-angiotensin II type 1 receptor antibody assessment

You may not qualify if:

• No simultaneous histological and serological assessment within the first year after transplantation, including i) absence of serum available for anti-angiotensin II type 1 receptor antibody assessment, and/or ii) absence of donor-specific anti-HLA antibody testing, and/or iii) absence of kidney allograft biopsy
• Inadequate kidney allograft biopsy according to the Banff classification for allograft rejection
• Combined transplantation

Sponsors & Collaborators

• Paris Translational Research Center for Organ Transplantation: lead
• Center for Cardiovascular Research Berlin: collaborator

Study Sites (2)

Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France

Paris, 75010, France

Location

Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France

Paris, 75015, France

Location

MeSH Terms

Conditions

Rejection, Psychology

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Study Officials

• Carmen Lefaucheur

  Paris Translational Research Center for Organ Transplantation

  PRINCIPAL INVESTIGATOR

• Alexandre Loupy

  Paris Translational Research Center for Organ Transplantation

  PRINCIPAL INVESTIGATOR

• Duska Dragun

  Clinic for Nephrology and Critical Care Medicine, Campus Virchow-Klinikum and Center for Cardiovascular Research, Medical Faculty of the Charité Berlin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 15, 2018
• Study Start: January 1, 2008
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: March 15, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)