Many advances have been made in the field of transplantation over the decades, but monitoring of patients after transplantation still faces challenges. This is why the KTD-innov project aims to develop a graft rejection prediction system that provides a probability of individual risks. Since the first transplant experiments at the beginning of the 20th century, what are the challenges of kidney transplantation today? Answer in figures
Kidney transplantation, A French story since the 19th century
In the history of medicine, the chapter dedicated to organ transplantation began at the end of the 19th century. Kidney transplantation plays an important role because it is the most performed organ transplantation in the world.
It was in Lyon that the pioneers of transplantation performed the first transplantations: Dr. Alexis Carrel, first of all, who in 1908 succeeded in the first kidney transplant in animals and demonstrated the effectiveness of cold to preserve organs; Dr. Mathieu Jaloubay, then, who experimented with the first kidney transplants in humans.
France will continue to play a major role in the field of kidney transplantation with the discovery of the compatibility of organs, thanks to the work of Doctors Dausset and Hamburger, of the Saint-Louis and Necker hospitals in 1962, and the establishment of bioethics laws in 1994 which place the well-being of the patient at the centre of medical research.
Since 1959, France has carried out nearly 90,000 kidney transplant operations, making kidney transplantation a treatment of choice for chronic kidney failure (CKD).
82,000 people with End Stage Renal Disease (ESRD) in France
There are two options when the disease reaches a terminal stage (End Stage Renal Disease - ESRD). The most common is hemodialysis. Today, this blood filtering technique remains constraining, as the patient must be dialysed over a period of 4 hours, 3 times a week.
The alternative for people with ESRD is a kidney transplant. The French High Authority for Health (HAS) considers transplantation to offer a better quality of life compared to dialysis. In fact, transplantation makes it possible to restore almost normal kidney activity while maintaining a lifestyle close to "normality".
More than €6,400: the monthly cost of End Stage Renal Disease (ESRD)
While dialysis can cost up to €7,200 per month, the cost of a kidney transplant is between €6,400 and €6,800. Kidney transplantation therefore represents a much more economical alternative to dialysis, with nearly €25 million saved on healthcare costs for all patients in France in 2018.
More than 3,500 kidney transplants performed each year in France
There were 3,567 new transplant patients in 2018, according to the French Biomedicine Agency, which is 215 fewer than in 2017, showing a decrease of the renal transplant activity of 11% in 2018. However, the growth rate of the number of people on the waiting list increases from year to year, with 19,625 patients waiting for a transplant in 2018, including 5,269 new patients on the waiting list, compared to 4,557 new patients in 2013. But the situation is improving as the number of transplants carried out in 2019 has risen to 3,641 operations.
1 graft available for 5 people on the waiting list
In 2018, for each available kidney, more than 5 people were on the waiting list. The HAS also estimates that only 31% of patients will receive a transplant in the first year after being placed on the list of potential recipients. Up to 15% will have to wait more than 5 years.
How can the shortage of organs for transplantation be tackled to ensure patients' comfort and chances of getting better?
85% of kidney transplants come from deceased donorS
The main source of organs comes from donations from deceased patients. In 2018, there were 1,881 brain-dead organ donors. The vast majority (93%) of these people donated at least one kidney. In 2006, organ donation became available for people who died from cardiac arrest. Today, thanks to this measure, 8% of grafts come from people who have died from heart failure.
Living donors make up 15% of donations. The French Biomedicine Agency considers this number to be low and due to the reluctance of patients to put their family and friends at risk as well as a lack of knowledge about how donors are medically monitored. Yet these donors are in better health than the general population, due to the clinicians' demands on donor monitoring.
Half the number of unallocated grafts in France than in the US
60% of transplants are kidney transplants
A 2018 study by the French Biomedicine Agency recorded 3,567 kidney transplants, 1,325 liver transplants and 450 heart transplants in one year. Despite the state of organ shortage, kidney remains the most widely transplanted organ.
On average, a kidney transplant survives 12.4 years
Today, the HAS measures graft survival time at 12.4 years, on average, after which the graft stops functioning properly. The patient must then undergo a new transplant or return to dialysis. The graft survival rate has been stable since 2010. In 2015, 1,032 transplant patients had to return to the waiting list of transplant candidates.
Graft failure is due, among other reasons, to immunological mechanisms leading to graft loss, and the field of transplantation still lacks robust assessments of immunological monitoring. It is a major issue for adapting treatment and increasing graft survival.
The KTD-innov project focuses on this issue, with the goal of developing a system for predicting rejection and providing a probability of individual risk of rejection. It will use a precision diagnostic system providing information regarding the activity and stage of the disease.
The KTD-innov consortium annual meeting took place on the 7th of February. The project partners came from different regions of France and met to review the project’s progress and up-coming steps.
The first news of this meeting: a significant milestone in the KTD-innov research project has just been reached with the recruitment of more than 800 kidney transplant patients in transplant centres in Bordeaux, Lyon, Montpellier, Nantes, Paris and Toulouse. The recruitment target has been met thanks to the patient volunteers who agreed to take part in this study. These patients will be monitored within the framework of the project for 12 months following their transplantation.
The next milestone is the collection and analysis of blood, urine and biopsy samples. The annual meeting was an opportunity to review overall coordination between the transplant centres - where samples are collected - and the analytical platforms.
This collaborative research project allows for the implementation of standardised collection processes between the different centres, thereby improving the quality of the samples and thus the quality of the analytical results.
In the meantime, over the past two years, the scientists involved in this French research project have been working to improve the analysis methods and the technical know-how of their teams. They have already optimised their ability to process samples, as well as the quality of the results that are and will be produced.
In the coming months, the researchers involved in the KTD-innov study will face many challenges. In particular, the compilation of analytical data from the samples in compliance with the existing regulations. With the integration of data collected from previous studies, the final database will contain monitoring information from more than 5,000 kidney transplants.
By 2022, the objective to be achieved is the development of an algorithm to use this database for research purposes. The design of a visual interface is also planned to compare the status of one transplant patient to another. The long-term goal is to deploy this algorithm to physicians as a diagnostic system to predict rejection of the kidney transplant.
Patients: the first link in the medical research chain
Both in Toulouse and at other research centres, the KTD-innov study could not succeed without close patient collaboration. Their involvement means researchers can obtain valuable data aimed at better understanding kidney transplant rejection and improving patient care and post-transplant monitoring.
As a recruitment centre for KTD-innov, Toulouse University Hospital's role is to establish this partnership with transplant patients. Prof. Kamar's team at Toulouse University Hospital provides information and collects samples from volunteer patients who are recruited when being cared for at the hospital. Although the samples are mostly among the usual necessary ones taken to monitor transplant patients and donors, a few extra samples are taken to provide data required for and specific to the study. All samples are sent to the analytical laboratories partnering with the KTD-innov project.
The Organ Transplant Unit (UTO) at Toulouse's Rangueil Hospital, coordinated by Prof. Kamar, is the only one in France to gather for adult kidney, pancreas, liver, lung and heart transplant departments all in one place. The Transplant Unit monitors almost 1500 patients and performed 293 grafts in 2016, making it one of the French leaders in the transplant field.
This expertise in transplant patient care and monitoring makes Prof. Kamar's service a key asset for the KTD-innov project. Toulouse's Rangueil Hospital is thus the 3rd center in terms of patients inclusions in the study.
A collaborative network serving patients and research
Toulouse University Hospital is part of the KTD-innov consortium that involves 9 partners (2 industrial and 7 hospitals and academic centres) involved in the KTD-innov study. Some partners are recruiting centres like Toulouse University Hospital and others are analysis platforms with the equipment required to extract the desired data from the samples collected: the presence of certain proteins and antibodies, plus transcriptomic data.
This collaborative drive between public and private stakeholders in multidisciplinary teams reflects French healthcare players' determination to improve care for patients who have received a kidney transplant.
University/hospital research projects like KTD-innov are funded by the French government: something that for Prof. Kamar is "needed for promoting the excellence of French research and its applications".
From 15 to 18 September 2019 the annual event of the European Society for Organ Transplantation (ESOT) will take place in Copenhagen.
ESOT is the European umbrella organisation under which all European transplant professionals are organized. The organisation trains and supports its members through various European programmes and events, such as the 2019 event in Copenhagen.
Several members of the KTD-innov consortium are fortunate to be able to participate in this event with the EU Train-ESOT symposium on 15 September. As well as through various conferences such as that of Dr. Hannah Kaminski of the University Hospital of Bordeaux on the "effect of antithymocyte globulin on CMV infection in renal transplant recipients". And a presentation by Professor Nassim Kamar at the Novartis symposium.
To follow the various presentations of the event, go to #ESOT2019 and @KTDinnov.
On April 15, the annual meeting of the KTD-innov consortium took place. This meeting allows all the partners to meet in order to review the progress of the study.
The meeting was also an opportunity to exchange views with representatives of the National Research Agency (ANR), which funded the KTD-innov research project.
Several of the partners took part in this day-long meeting, including Sophie Brouard and Alexandre Loupy, the two project coordinators.
The success of this project depends in particular on the quantity and quality of data collected from volunteer patients. To date, more than 400 patients have accepted to be part of this study.
The objectives for the next steps have been set. New patients will be recruited throughout the coming year. And the analysis of the collected samples will soon begin, 50% of the samples should be analyzed by the end of 2019.
The researchers involved in the KTD-innov study will work to solve many challenges in the coming months. The data collected must be consolidated in a homogenized database that meets international security standards.
In the next few months, scientists involved in this French research project will try to identify patients at risk for allograft rejection. Bioinformatic tools will be used to analyze results from collected samples and data. A tool will then be provided to clinicians to assist the medical decision process in order to improve patients’ follow-up.
Collaborative and sustainable research on graft rejection in Bordeaux
The Bordeaux University Hospital's participation in the KTD-innov project was a natural collaboration between Prof. Couzi and the two co-coordinators of the project, Drs Alexandre Loupy and Sophie Brouard.
Thanks to this funding, the Bordeaux University Hospital has joined a partnership with other university hospitals, such as those in Lyon, Nantes, Toulouse, Montpellier and the APHP.
At the Bordeaux University Hospital, the team of Prof. Couzi and Prof. Merville is conducting translational research with the CNRS-UMR 5164 ImmunoConcept unit led by Dr. Julie Déchnet-Merville on cytomegalovirus infection, an infection particularly common in renal transplant patients.
Other research themes of the service include humoral rejection mediated by anti-HLA antibodies, which is at the centre of the KTD-innov study. The participation of the University Hospital of Bordeaux in the KTD-innov project will therefore help to consolidate a team of researchers thanks to stable funding for a project over several years.
Within the team at the University Hospital of Bordeaux led by Prof. Couzi and Prof. Merville, 11 people are working on the KTD-innov project, including three clinical research associates. Accompanied by several co-investigators, they are responsible for accompanying transplant patients in their voluntary participation in the KTD-innov study.
The collection of this data is essential for the progress of the research project, because it is the basis on which it is based. As in six transplant centers in France, the team of Prof. Couzi and Merville collects clinical, biological, immunological and molecular data from kidney transplant patients. These data are then anonymized before being analyzed by Inserm, Nantes University Hospital, APHP and Bio-Rad. It is by analyzing these data that researchers hope to gain a better understanding of the complex causes of renal transplant rejection.
The KTD-innov project has a great impact on the different parties involved in the research
For Prof. Couzi, the KTD-innov project has enormous benefits for patients because it offers a better definition of the diagnosis of rejection and should lead to improved patient care. Today, as life expectancy increases, the life expectancy of a transplanted kidney is only about a dozen years on average. It is therefore urgent to better diagnose the signs of rejection in order to better manage them and thus prolong the life of kidney transplants.
The project has clear societal benefits, particularly in addressing the current shortage of organ donation. More and more patients around the world need an organ transplant, but unfortunately the supply is not able to meet this increased demand. That is why this project to predict graft rejection is important, not only on a French scale but also on a global scale.
Research for patients in France and around the world
The KTD-innov project will generate knowledge in kidney transplantation that will be useful for medical professionals in the decades to come. It also has the potential to disrupt the way kidney transplants are treated in the short and long term.
The success of the project favors the financing of other large scale and high potential studies. The consortium has a "significant impact on French scientific reputation in kidney transplantation". It therefore contributes to strengthening the dynamism of research in Bordeaux, and of French research centres in general, in the field of kidney transplantation, thus strengthening their positions as major players in the world.
The American Transplant Congress, or ATC, is the annual joint meeting between the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST). The aim of the congress is to promote the exchange of information and innovative technologies between the various professionals in the transplantation sector: surgeons, transplant surgeons, nurses, as well as all professionals in the transplantation field.
This year, the congress will take place between June 1 and 5, 2019 in Boston, USA. During the various conferences and presentations, many researchers will express themselves on their discoveries in the transplantation field. Among them, the scientists of the KTD-innov consortium, represented by Marc Raynaud, will present the progress of the project's French research in a presentation entitled: "Population-based modelling of prototypes and determinants of allograft function trajectories after kidney transplantation: Impact on patient monitoring and risk stratification". A presentation to follow via social networks on June 2 at 8:42 pm Paris time, thanks to the hashtag #ATC2019Boston and on @KTDinnov.
For more information, you can find the full programme of ATC 2019 here.
New research conducted by the Paris Translational Research Center for Organ Transplantation team could help clinicians determine which patients will have a disease that usually occurs after a kidney transplant and which are at high risk of transplant failure. The results are published in the prestigious Journal of the American Society of Nephrology (JASN).
Transplant glomerulopathy is a disease associated with the loss of a kidney transplant. There is currently no treatment for this heterogeneous disease.
This research was able to identify and characterize five distinct patient groups, each with different graft survival outcomes.
This research approach has been translated into a tool accessible to clinicians to assess the risk of graft loss in their patients. This will allow the individualization of patients' treatments according to their group.
World Kidney Day, promoted in France by the Kidney Foundation, will take place on March 14. This year, the theme chosen was inequalities in the prevention, early detection and treatment of kidney disease worldwide, under the slogan "Healthy kidneys for everyone, everywhere".
According to the WHO, chronic kidney disease has become a public health issue affecting 10% of the world's population. In France, 3 million people suffer from it and 87,000 of them are treated by dialysis or receive a kidney transplant. For Health Insurance, the cost of this care represents 2% of its total expenses, or €4 billion per year.
This is why the Future Investments programme is providing €9 million to support the KTD-innov research project.
Research responds to a real need of patients
For people with severe chronic kidney disease, a transplant is often the ideal choice because it is less restrictive and less expensive than dialysis. Unfortunately, in France, less than 4,000 people a year are lucky enough to receive a new kidney, and 1,500 people are still on waiting lists.
The law of 26 January 2016 on organ donation has made it possible to generalise it but is not enough to sufficiently reduce the list of patients waiting for a kidney transplant. And it happens regularly that patients who have already had a transplant need a new organ a few years after their transplant. That is why the KTD-innov project is looking for a solution to make the graft viable for longer. This solution will allow a personalized medical follow-up of transplanted patients.
Innovation in research
The KTD-innov project offers a unique approach that combines clinical, biological, immunological and molecular data from the patient. It allows a global vision of the patient and a unique analysis in the world.
Thanks to funding from the French government, KTD-innov will improve knowledge and predict the success of transplants. It is thanks to this innovation that patients can already expect an individualization of their treatment and an increase in the life of their graft by 2022.
Follow the World Day campaign on Twitter
The 2019 Cutting Edge of Transplantation (CEoT) took place between the 21st and the 23rd of February 2019 in Phoenix, USA. This year’s theme was “No size fits all: uncovering the potential of personalized transplantation”.
Their goal for their meeting each year is to see the advancement of individualized care for transplant patients through new algorithms or practices, for the duration of their transplant journey.
That is why, Dr. Alexandre Loupy presented the work of the KTD-innov team with two oral presentations, presenting the advancement of the research and how it could help transplant patients in the future by minimizing rejection risks.
The CEoT is a meeting organized each year since 2013 by the American Society of Transplantation (AST). The organization was founded in 1982 and now counts 3 800 health professionals. Their goal is to promote both the field of transplantation and patient care through research, education, advocacy, and organ donations.
To elucidate the mechanisms of success or failure of a kidney transplant, KTD-innov collects, centralizes and analyses clinical, biological and immunological data from thousands of kidney transplant patients in France.