Trajectories of Glomerular Filtration Rate and Progression to End Stage Renal Disease After Kidney Transplantation

NCT ID: NCT04226859

Last Updated: 2020-01-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

14000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2000-01-31

Study Completion Date

2020-06-30

Brief Summary

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The gold standard for characterizing chronic kidney disease (CKD) is the glomerular filtration rate (GFR), which is commonly estimated in both native and transplanted kidneys for patient monitoring and therapeutic management and ultimately guides decision-making about whether a patient needs renal replacement therapy. In particular, the National Kidney Foundation has defined CKD stages according to estimated GFR (eGFR) values and in several studies, the eGFR slope or change has been found to be strongly associated with end stage renal disease (ESRD).

However, little is known about the heterogeneity of eGFR evolution in time - i.e. eGFR trajectories - and the related progression to ESRD and death. To date, no studies have investigated eGFR trajectories in diversified cohorts and populations worldwide, although this approach could provide a better understanding of CKD evolution and hence improve risk stratification. In addition, determinants of eGFR trajectories remain poorly described.

An unsupervised approach could allow examining eGFR trajectories over time and could lead to the identification of patient groups according to the probability of the progression of their kidney disease.

Therefore, this study aims:

1. To identify the long-term eGFR trajectories after kidney transplantation using latent class mixed models;
2. To identify the clinical, immunological, histological and functional determinants of the eGFR trajectories using multinomial regressions;
3. To investigate the associations of the eGFR trajectories with the progression to ESRD and death.

Based on the results, the investigators will provide an easily accessible tool to calculate personalized probabilities of belonging to eGFR trajectories after kidney transplantation, by using datasets from prospective cohorts and post hoc analysis of randomized control trial datasets.

Detailed Description

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Background

Chronic kidney disease (CKD) now affects 850 million individuals worldwide, exceeding the global prevalence of diabetes, cancer and HIV/AIDS. In addition, end-stage renal disease affects 7.4 million individuals and mortality rate for individuals burdened by kidney disease is now estimated at 5 to 10 million individuals each year. Therefore, developing better diagnostic and treatment approaches for the kidney disease epidemic is a global priority, as leading professional societies and health agencies have emphasized (the US Food \& Drug Administration, the National Kidney Foundation, the European Medicines Agency, the European Society of Organ Transplantation, the American Society for Transplantation and the American Society of Transplant Surgeons).

However, current approaches for investigating the relationship between eGFR course and outcomes such as ESRD and mortality have been limited by registries with an overall lack on granular data, including infrequent eGFR measurements for a single patient and convenience clinical samples. An unsupervised longitudinal approach to determine patient eGFR evolution may bring an original perspective to the traditional clinical interpretation of kidney function based on limited eGFR measurements, short-term follow-up, and standard statistical approach.

Main Outcome(s) and Measure(s)

* eGFR trajectories
* Determinants of eGFR trajectories
* Associations of eGFR trajectories with ESRD and death
* Prediction system that will provide the personalized probabilities of belonging to eGFR trajectories

Conditions

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Kidney Transplant Failure Kidney Function Issue

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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No intervention

Kidney recipients aged over 18 and of all sexes recruited from 2000 in European and North American centers, who have eGFR follow-up and data from protocol and for cause biopsies available for allograft survival assessment; Randomized controlled trials conducted over the past 20 years with available data on protocol biopsy within the first year and follow up clinical, biological and histological data.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Kidney recipients transplanted after 2000
* Kidney recipients over 18 years of age
* Kidney recipients with at least two eGFR measurements after transplantation

Exclusion Criteria

* Combined transplantation
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Paris Translational Research Center for Organ Transplantation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alexandre Loupy, Professor

Role: PRINCIPAL_INVESTIGATOR

Paris Translational Research Center for Organ Transplantation

Locations

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Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status ENROLLING_BY_INVITATION

Department of Surgery, Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Site Status ENROLLING_BY_INVITATION

William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic

Rochester, Minnesota, United States

Site Status ENROLLING_BY_INVITATION

Albert Einstein College of Medicine, Renal Division Montefiore Medical Center, Kidney Transplantation Program

New York, New York, United States

Site Status ENROLLING_BY_INVITATION

Virginia Commonwealth University School of Medicine

Richmond, Virginia, United States

Site Status ENROLLING_BY_INVITATION

Department of Nephrology and Renal Transplantation, University Hospitals Leuven

Leuven, , Belgium

Site Status ENROLLING_BY_INVITATION

Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, School od Medicine University of Zagreb

Zagreb, , Croatia

Site Status ENROLLING_BY_INVITATION

Department of Nephrology, Centre Hospitalier Universitaire de Montpellier

Montpellier, , France

Site Status ENROLLING_BY_INVITATION

Nephrology Dialysis Transplantation Department, University of Lorraine, Centre Hospitalier Universitaire de Nancy

Nancy, , France

Site Status ENROLLING_BY_INVITATION

Centre Hospitalier Universitaire de Nantes

Nantes, , France

Site Status ENROLLING_BY_INVITATION

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

Paris, , France

Site Status RECRUITING

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

Paris, , France

Site Status RECRUITING

Department of Transplantation, Nephrology and Clinical Immunology, Hôpital Foch

Suresnes, , France

Site Status ENROLLING_BY_INVITATION

Department of Nephrology and Organ Transplantation, Centre Hospitalier Universitaire Rangueil

Toulouse, , France

Site Status ENROLLING_BY_INVITATION

Bretonneau Hospital, Nephrology and Immunology Department

Tours, , France

Site Status ENROLLING_BY_INVITATION

Countries

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United States Belgium Croatia France

Central Contacts

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Alexandre Loupy, Professor

Role: CONTACT

Marc Raynaud

Role: CONTACT

+33613493009

Facility Contacts

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Carmen Lefaucheur, MD

Role: primary

Alexandre Loupy, Professor

Role: primary

+33612491082

Related Links

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https://www.paristransplantgroup.org

Paris Transplant Group Website

Other Identifiers

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TRAJAKT

Identifier Type: -

Identifier Source: org_study_id

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