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

Conditions
Kidney Function Issue
Kidney Transplant Failure
Registration Number
NCT04226859
Lead Sponsor
Paris Translational Research Center for Organ Transplantation
Brief Summary

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

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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
14000
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
eGFR trajectoriesUp to 10 years after kidney transplantation

eGFR trajectories probabilities, calculated from a prediction system (based on clinical, histological, immunological, and functional factors) assessed at 1-year post transplantation.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (15)

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

🇺🇸

Los Angeles, California, United States

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

🇺🇸

Rochester, Minnesota, United States

Department of Surgery, Johns Hopkins University School of Medicine

🇺🇸

Baltimore, Maryland, United States

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

🇺🇸

New York, New York, United States

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

🇫🇷

Nancy, France

Department of Nephrology and Renal Transplantation, University Hospitals Leuven

🇧🇪

Leuven, Belgium

Department of Nephrology, Centre Hospitalier Universitaire de Montpellier

🇫🇷

Montpellier, France

Virginia Commonwealth University School of Medicine

🇺🇸

Richmond, Virginia, United States

Centre Hospitalier Universitaire de Nantes

🇫🇷

Nantes, France

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

🇫🇷

Paris, France

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

🇫🇷

Paris, France

Department of Nephrology and Organ Transplantation, Centre Hospitalier Universitaire Rangueil

🇫🇷

Toulouse, France

Department of Transplantation, Nephrology and Clinical Immunology, Hôpital Foch

🇫🇷

Suresnes, France

Bretonneau Hospital, Nephrology and Immunology Department

🇫🇷

Tours, France

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

🇭🇷

Zagreb, Croatia

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