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

Multicenter International Observational Study to Identify eGFR Trajectories and Their Determinants, and to Build a Multidimensional Prediction System to Predict the Probabilities of Belonging to eGFR Trajectories

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.

Study Overview

• Status: Unknown
• Conditions: Kidney Transplant Failure; Kidney Function Issue
• Intervention / Treatment: Other: No intervention

Detailed Description

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

• Study Type: Observational
• Enrollment (Anticipated): 14000

Contacts and Locations

• Study Contact: Name: Alexandre Loupy, Professor; Email: alexandre.loupy@inserm.fr
• Study Contact Backup: Name: Marc Raynaud; Phone Number: +33613493009; Email: mrayna06@gmail.com

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Enrolling by invitation
    • Department of Nephrology and Renal Transplantation, University Hospitals Leuven
• Croatia
  • Zagreb, Croatia, 10000
    • Enrolling by invitation
    • Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, School od Medicine University of Zagreb
• France
  • Montpellier, France, 34295
    • Enrolling by invitation
    • Department of Nephrology, Centre Hospitalier Universitaire de Montpellier
  • Nancy, France, 54035
    • Enrolling by invitation
    • Nephrology Dialysis Transplantation Department, University of Lorraine, Centre Hospitalier Universitaire de Nancy
  • Nantes, France, 44093
    • Enrolling by invitation
    • Centre Hospitalier Universitaire de Nantes
  • Paris, France, 75010
    • Recruiting
    • Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris
    • Contact: Carmen Lefaucheur, MD
  • Paris, France, 75015
    • Recruiting
    • Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris
    • Contact: Alexandre Loupy, Professor; Phone Number: +33612491082; Email: alexandre.loupy@inserm.fr
  • Suresnes, France, 92150
    • Enrolling by invitation
    • Department of Transplantation, Nephrology and Clinical Immunology, Hôpital Foch
  • Toulouse, France, 31059
    • Enrolling by invitation
    • Department of Nephrology and Organ Transplantation, Centre Hospitalier Universitaire Rangueil
  • Tours, France, 37000
    • Enrolling by invitation
    • Bretonneau Hospital, Nephrology and Immunology Department
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Enrolling by invitation
      • Department of Medicine, Division of Nephrology, Comprehensive Transplant Center, Cedars Sinai Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Enrolling by invitation
      • Department of Surgery, Johns Hopkins University School of Medicine
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Enrolling by invitation
      • William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic
  • New York
    • New York, New York, United States, 10467
      • Enrolling by invitation
      • Albert Einstein College of Medicine, Renal Division Montefiore Medical Center, Kidney Transplantation Program
  • Virginia
    • Richmond, Virginia, United States, 980663
      • Enrolling by invitation
      • Virginia Commonwealth University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Kidney recipients aged over 18 and of all sexes recruited from 2000 in European and North American centers, who have eGFR repeated measurements, data from protocol and for cause biopsies, as well as immunological, clinical, functional parameters and survival data for allograft and patient survival assessment. Additional kidney recipients from RCTs with longitudinal data including baseline and follow-up clinical, functional, immunological and histological data.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR trajectories	eGFR trajectories probabilities, calculated from a prediction system (based on clinical, histological, immunological, and functional factors) assessed at 1-year post transplantation.	Up to 10 years after kidney transplantation

Collaborators and Investigators

• Sponsor: Paris Translational Research Center for Organ Transplantation
• Investigators: Principal Investigator: Alexandre Loupy, Professor, Paris Translational Research Center for Organ Transplantation

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2000
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2020

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 13, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Kidney Transplantation; Graft Survival; Glomerular Filtration Rate; Trajectories
• Other Study ID Numbers: TRAJAKT

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