Anti-HLA Immunization And Immunosuppressive Therapy Management In Kidney Transplant Patients Returning to Dialysis

Evolution of Anti-HLA Immunization According to Immunosuppressive Therapy Management Modalities in Kidney Transplant Patients Returning to Dialysis in Lorraine Between January 2007 and December 2019

This study is an analytical observational retrospective cohort study. It is a single-center study conducted in the Nancy University Hospital.

End stage renal disease is the ultimate stage of the chronic kidney disease. Patients need extra-renal replacement techniques. Kidney transplantation is the most effective option for survival, quality of life and costs.

Then long-term immunosuppressive agents are required to prevent allograft rejection and improve graft survival.

The number of patients who return in dialysis after graft loss is increasing and accounts for 10% of incident dialysis patients and 14% of patients on the kidney transplant waiting list registered in 2019. This population may develop complications induced by end-stage renal disease and adverse events related to prolonged exposure to immunosuppressive agents.

There are currently no formal guidelines on the management of immunosuppressive agents when patients return to dialysis. Reduction or discontinuation of therapy appears to decrease cardiovascular, infectious, and neoplastic complications. However, continuing these treatments may limit anti-HLA sensitization which may access to retransplantation.

Only a few low-powered cohort studies have evaluated the impact of the management of immunosuppressive therapy on the HLA-sensitization.

The hypothesis of our study is that the continuation of immunosuppressive agents when patients return in dialysis may limit anti-HLA sensitization. Therefore, access to retransplantation could be facilitated.

The main objective is to compare the evolution of anti-HLA sensitization according to the management of immunosuppressive treatment after the return in dialysis (maintenance, reduction, cessation).

Secondary objectives are time to re-transplantation for patients on the transplant waiting list, survival of the new graft, patient survival, and dialysis complications (cardiovascular, infectious and neoplastic complications).

Study Overview

• Status: Active, not recruiting
• Conditions: Kidney Transplantation; Dialysis; Immunosuppressive Agents; HLA Sensitization
• Intervention / Treatment: Drug: management of immunosuppressive therapy

Detailed Description

Cohort constitution :

The cohort of patients returning to dialysis after graft loss is extracted from the REIN (Réseau Epidémiologique et Information en Néphrologie) Lorraine registry, which follow all patients in end-stage renal failure under replacement therapy in the Lorraine region since 2001.

Patients returning to dialysis after graft loss between 1st January 2007 and 31st December 2019 are extracted from the register and included.

From this cohort, 3 groups were created according to the management of their immunosuppressive therapy : maintenance, reduction, and discontinuation. The immunological data of the patients are recovered from the HLA laboratory of the Nancy University Hospital.

• Study Type: Observational
• Enrollment (Anticipated): 430

Contacts and Locations

Study Locations

• France
  • Lorraine
    • Nancy, Lorraine, France, 54000
      • Central HNF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The cohort of patients returning to dialysis after graft loss is extracted from the REIN Lorraine registry. Patients returning in dialysis after graft loss between 1st January 2007 and 31st December 2019 are included.

From this cohort, 3 groups were created according to the management of their immunosuppressive therapy : maintenance, reduction, and discontinuation. The immunological data of the patients are recovered from the HLA laboratory of the Nancy University Hospital.

Description

Inclusion Criteria:

• Patients included in the Lorraine regional REIN registry over the period 2007-2019,
• Returning in dialysis after a kidney transplantation, with a living or deceased donor.
• On haemodialysis or peritoneal dialysis.
• Registered or not on the waiting-list for retransplantation

Exclusion Criteria:

• Patients with graft dysfunction receiving a pre-emptive retransplantation
• Absence of serum tested for anti-HLA (human leukocyte antigen) antibodies after the return to dialysis.
• No information on immunosuppressive agents

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

kidney transplant patients returning to dialysis after graft loss; This cohort contains kidney transplant patients returning to dialysis after graft loss in Lorraine between 1 January 2007 and 31 December 2019. They are identified by the REIN registry of the Lorraine region. The REIN registry is a national database that contains multiple information on patients with chronic end-stage renal disease (type of nephropathy, type of replacement therapy, comorbidities).

Drug: management of immunosuppressive therapy; 3 groups : Discontinuation of immunosuppressive agents; Reduction of immunosuppressive agents; Maintenance of immunosuppressive agents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of the evolution of anti-human leucocyte antigen sensitization according to the management of immunosuppressive therapy	Evolution of the panel reactive antibody evolution 6 months after the return in dialysis	baseline = return in dialysis, t1=6 months after return in dialysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients survival	Patient survival after return in dialysis	baseline = return in dialysis, end of follow up = death or last follow-up or 31 december 2020
New transplantation	Retransplantation after return in dialysis	baseline = return in dialysis, end of follow up = death or last follow-up or 31 december 2020
Graft Survival after retransplantation	Graft Survival after retransplantation	baseline = return in dialysis, end of follow up = death or last follow-up or 31 december 2020
Incidence of infectious, neoplastic and cardiovascular events	Incidence of infection, neoplastic and cardiovascular events after return in dialysis	baseline = return in dialysis, end of follow up = 1 year after return in dialysis

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2022
• Primary Completion (ANTICIPATED): March 30, 2022
• Study Completion (ANTICIPATED): September 1, 2022

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: March 8, 2022
• First Posted (ACTUAL): March 16, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: kidney transplantation; immunosuppressive agents; graft loss; HLA antibodies; retransplantation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Immunosuppressive Agents
• Other Study ID Numbers: 2021PI192

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No