Kidney Transplant Failure

NCT ID: NCT01296061

Last Updated: 2019-09-06

Basic Information

• Recruitment Status: TERMINATED
• Total Enrollment: 270 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2017-07-31

Brief Summary

Primary Hypotheses:

1. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have more deaths than patients who discontinue these drugs

2. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have more hospitalizations for sepsis than patients who discontinue these drugs

3. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have fewer rejection events than patients who discontinue these drugs

Secondary Hypotheses:

1. Patients who undergo elective nephrectomy (to remove the failed kidney transplant) will have fewer deaths than those who retain the failed kidney transplant

2. Patients who undergo elective nephrectomy (to remove the failed kidney transplant) will have fewer hospitalizations for sepsis than those who retain the failed kidney transplant

3. Among patients who retain the failed kidney transplant, those who continue immunosuppressant medication will have lower levels of allosensitization (anti-HLA antibodies) than those who discontinue these drugs

4. Patients who undergo elective nephrectomy will have higher levels of allosensitization (anti-HLA antibodies) than patients who retain the failed kidney transplant

Detailed Description

Transplantation is the best treatment for patients with end stage kidney disease.1 However, despite the development of powerful immunosuppressant medications, transplantation still does not provide most patients with lifelong freedom from dialysis. The half-life (time to 50% failure) of a deceased donor kidney transplant is only 10.5 years.4, 5 As the number of prevalent patients who received a transplant more than a decade ago increases, the number of patients with failing transplants who must either return to dialysis or undergo repeat transplantation is also rapidly increasing.6 Repeat transplantation is clearly the best option for these patients.8 However, in Canada, only 10% of patients with first transplant failure will receive a second transplant.9 Consequently transplant failure is now the fifth leading individual cause of dialysis initiation in Canada.6, 10 Survival after transplant failure is very poor, with 40% mortality in the first 5 years after initiation of dialysis.9, 11, 12 In comparison, the 5 year mortality of de novo incident dialysis patients, including those who are not even transplant candidates, is 50%, 6, 10while that of first transplant recipients is < 10%.6, 10 However, the unique characteristics of the transplant failure population limit the validity of such comparisons with other chronic kidney disease patients. Transplant failure patients were initially selected to undergo transplantation because of their favorable age and health status, and thus differ from unselected de novo incident dialysis patients. Similarly, unlike first time transplant recipients, transplant failure patients already have prolonged exposure to immunosuppressant medications that can increase the risk of cardiovascular disease, cancer and metabolic bone disease. Notwithstanding these issues, we and others have published a number of studies documenting the poor outcomes, and stressing the need for prospective studies in this unique subset of chronic kidney disease patients.9, 12-16 To date, no study has systematically examined this patient population and basic questions about how to manage the failed kidney allograft remain. Although there are some clear indications for emergent surgical removal of the failed allograft (nephrectomy), the elective use of nephrectomy is highly variable and poorly described.17-19 Acute immunologic injury (rejection) in the failed transplant can occur as long as the allograft remains in situ, and can cause both local and systemic symptoms. In addition, the failed allograft may promote chronic inflammation leading to malnutrition, anemia and cardiovascular disease.20, 21 No prospective studies have examined whether nephrectomy and discontinuation of immunosuppressant medications is preferable to retaining the failed allograft. If the allograft is retained, it is not known whether the risk of continued exposure to immunosuppressant medications outweighs the risk of acute rejection or chronic inflammation when these drugs are discontinued. Importantly, management of the failed allograft can impact allosensitization,22-24 a primary determinant of a patient's ability to undergo repeat transplantation.

This prospective observational study is a necessary first step in defining the optimal management strategy for this unique and growing patient population. The primary and secondary research questions will determine the association of (i) immunosuppressant drug use and (ii) elective nephrectomy with clinical outcomes including death, sepsis, and rejection. Importantly, the study will also determine the association of these exposures with allosensitization (anti-HLA antibodies). The information obtained will inform the design of future interventional studies that will definitively define how to best manage these complex patients.

Conditions

Acute Graft Rejection; Renal Failure Chronic Requiring Dialysis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Failed Kidney Transplant

Adults ≥ 18 years, initiating chronic dialysis

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

Inclusion Criteria:Patients ≥ 18 years, who initiate chronic dialysis treatment after failure of a first kidney transplant

Exclusion Criteria:Recipients of a multi-organ transplant (e.g. kidney- pancreas transplant), and patients unable to provide informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

St. Paul's Hospital, Canada

OTHER

Sponsor Role: collaborator

Vancouver General Hospital

OTHER

Sponsor Role: collaborator

Kingston Health Sciences Centre

OTHER

Sponsor Role: collaborator

University of Saskatchewan

OTHER

Sponsor Role: collaborator

University of Calgary

OTHER

Sponsor Role: collaborator

University of Manitoba

OTHER

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: collaborator

St. Joseph's Healthcare Hamilton

OTHER

Sponsor Role: collaborator

London Health Sciences Centre

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: collaborator

Maisonneuve-Rosemont Hospital

OTHER

Sponsor Role: collaborator

Centre hospitalier de l'Université de Montréal (CHUM)

OTHER

Sponsor Role: collaborator

CHU de Quebec-Universite Laval

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Greg Knoll, MD

Role: PRINCIPAL_INVESTIGATOR

U of Ottawa, The Ottawa Hospital, OHRI

John Gill, MD

Role: PRINCIPAL_INVESTIGATOR

UBC, St Paul's Hospital Vancouver, BC

Locations

The Ottawa Hospital

Ottawa, Ontario, Canada

Countries

Canada

Other Identifiers

CIHR FRN MOP-102732

Identifier Type: -

Identifier Source: org_study_id