PROACT Trial

The Pediatric RandOmized Application of uCXCL10 monitoring in Transplantation (PROACT) trial

Project Summary

A pilot clinical trial to evaluate the feasibility and acceptability of: A prospective, unblinded, randomized-controlled, multicenter biomarker intervention trial of a urinary CXCL10 clinical surveillance program in pediatric kidney transplant recipients for early ascertainment and treatment of subclinical allograft inflammation and preservation of kidney transplant function (PROACT Trial)

Kidney transplant rejection happens when the body’s immune system attacks your kidney transplant. Over time, rejection can lead to serious complications like kidney damage and eventually kidney transplant failure. Doctors prescribe medications known as immunosuppressants to prevent this immune system attack. Too much can sometimes increase side effects or infections. But too little risks kidney rejection. The right amount of immunosuppressant medications is different for everyone. Kidney function is monitored with routine blood tests to measure creatinine and other markers. Transplant recipients also undergo routine kidney biopsies to assess the tissue health of the transplanted organ. Current monitoring strategies don’t always give your doctors all the information they need. As a result, additional testing, including biopsies, may be recommended.These tests can be invasive and uncomfortable for patients, especially pediatric transplant recipients. 

Urine CXCL10 is a potential new test for kidney monitoring after a transplant. CXCL10 is a small protein that is produced by your body's immune system when there is inflammation. When inflammation in the kidney is caused by early rejection, higher levels of CXCL10 can be found in the urine. Urine CXCL10 also goes higher with different kidney infections. All causes of inflammation in the kidney can lead to kidney damage.

Funding support from Canadian Institutes of Health Research (CIHR).

For more information, email sotresearch@bcchr.ca or view our study brochure. 

Project Status

Status: Active, data collection ongoing
Study Start Date: November 1, 2024
Study End Date: May 31, 2027

Study Enrolment Status: Enrolment closed
Start Date: February 1, 2025
End Date: May 9, 2025

Project Team

Principal Investigator

Dr. Tom Blydt-Hansen
 
Co-Investigators

Dr. Li Wang, University of British Columbia
Dr. Suzanne Vercauteren, University of British Columbia
Dr. Aviva Goldberg, University of Manitoba
Dr. Lusia Sepiashvilli, University of Toronto
Dr. Chia Wei Teoh, University of Toronto
Dr. Ashlene McKay, University of Toronto
Ella Chan, BSc

Research Team Members

BC Children's Hospital:
Monica Ho, Research Coordinator
Amy Thachil, Research Assistant
Phillip Ly, Research Assistant

The Hospital for Sick Children:
Zeenat Un Nisa, Research Coordinator
Linda Wright, Research Coordinator 

HSC Winnipeg Children's Hospital:
Reyhane Aliakbari, Research Coordinator 

Enrolment Eligibility Criteria

1. Prevalent pediatric kidney transplant recipients (<19 years at transplantation) who are more than 6 months after transplant, with informed consent and assent.
2. Must be available to follow-up for two years after initiation of urinary CXCL10 monitoring

For more information, email sotresearch@bcchr.ca or view our study brochure.

PROACT Newsletter

Click on the button below to read our April 2025 newsletter. 

PROACT Study Newsletter

Frequently Asked Questions

What are ways to minimize and reduce the risk of rejection after a kidney transplantation?

Question from Shawn (transplant recipient)

Answer: Each person’s risk for rejection is a little different. Risk depends on things like previous rejection episodes, how long it has been since transplant, the need sometimes to reduce immune suppressant medications because of infection, how well the donor and recipient are matched and a person’s innate immune function. It is important to talk to your transplant team, to understand what that risk is like for you. Amongst the most important things, and one which you can help to control, is to ensure you have a steady level of immune suppression, which comes from taking your medications regularly and on time. If there is rejection, it is also important to treat it as early as possible. So, if there are signs that there might be rejection, your transplant team will recommend a kidney biopsy to make sure one way or the other.

Would the efficacy of this new study be used as a replacement for future biopsies or used as a bridge step prior to doing a more invasive procedure?

Question from Shawn (transplant recipient)

Answer: Blood creatinine (which estimates kidney function) monitoring can pick up rejection when it is more severe or advanced but can miss milder or early rejection. This is especially true for children, who often receive larger adult sized kidneys into their smaller bodies, so it can take a large change in kidney function to show up as a small change in creatinine. Kidney biopsy is still the best test to confirm rejection and is generally safe However, we would like to do fewer screening kidney biopsies, if we can replace them with a less invasive test for regular monitoring. If a less invasive test is found to be effective, it could reduce the complications from biopsies, reduce time spent in the hospital and allow for more frequent monitoring of rejection risk. The urine CXCL10 test is a good option because it can pick up rejection that is earlier and milder, which is missed by blood creatinine testing. There are other similar tests being evaluated right now. They could also be used to monitor response to treatment of rejection. We don’t know yet if we will be able to completely replace kidney biopsies. The goal of this study is to help us answer some of these questions.

What biomarkers are currently used to detect kidney transplant rejection?

Question from Shawn (transplant recipient)

Answer: There are many “biomarkers” that we use now, and some that are still in research. Any test that tells us about possible risk for rejection can be considered a biomarker. Blood creatinine can be considered a biomarker because it tells us about kidney function, and we know that kidney failure (lower function, higher creatinine) can happen if there is progressive rejection. Low levels of immune suppression medication (like tacrolimus) is also a kind of biomarker. When the levels are persistently low, we know the risk for rejection is getting higher. There are other blood tests that look for signs of kidney damage (called cell-free DNA) or look for signs of immune system activation (called gene expression tests) that are being tested. There are also other urine tests (called metabolites) that are being tested. It may be that using some of these tests together will be even better than any single test. Many researchers are trying to find better biomarkers for rejection, so that we can be pick up rejection as early as possible to minimize or prevent kidney transplant injury with proper treatment.

How is kidney transplant rejection diagnosed currently?

Question from Shawn (transplant recipient)

Answer: Kidney rejection diagnosis depends on evaluating the kidney tissue that is obtained with a biopsy. A kidney biopsy is currently the only way to get this type of detailed information. The tissue is stained with special dyes that help show us the details of the tiny kidney filters, tubules, blood vessels and any invading white blood cells. We evaluate them using a microscope and the amount of white blood cells (inflammation) in the kidney is rated for severity. The different structures in the kidney that are affected like the filters, blood vessels and tubules are checked to see what is affected by the inflammation. That tells us what kind of rejection is going on. All of this information is reported by the biopsy specialist (pathologist) to the kidney transplant team, who can use the information to come up with a treatment plan.

Are there other non-invasive ways to monitor kidney transplant rejection?

Question from Shawn (transplant recipient)

Answer: A kidney biopsy test is referred to as “invasive” because it requires a scheduled procedure, time to recover and a sample of the kidney that could be complicated by bleeding. Rarely a biopsy could cause injury to the kidney transplant. “Non invasive” testing usually refers to blood or urine tests, which can be done quickly, with minimal discomfort and without risk to the kidney transplant. Current non-invasive ways to monitor for rejection risk include blood creatinine testing, drug levels of immune suppression medication and urine protein testing. Blood creatinine tells us about kidney function and goes higher when the kidney function is failing. Drug levels (e.g. tacrolimus levels) tell us how well the kidney is being protected by the medication and raise concern when they are staying too low. Urine protein tells us about damage to the tiny kidney filters (glomeruli) and is elevated when there is antibody-mediated rejection. We can also do testing for antibodies against the kidney transplant (known as “donor specific antibody” or DSA), which also raises concern for chronic forms of rejection. All of these tests are currently used to monitor for kidney rejection. There are several other new tests being evaluated by researchers, which we hope will continue to improve our ability to pick up rejection earlier and more sensitively.

What are the risks of kidney transplant rejection, and how common is it in children?

Question from Annie (caregiver of transplant recipient)

Answer: Everyone with a kidney transplant is at risk for rejection. The risk is related to how well matched the kidney donor was to the person with a transplant, along with other factors. We call this human leukocyte antigen (HLA) or tissue type matching. A perfect match is very rare. A living donor transplant from a family member will usually be a much better match, because the tissue types (HLA) are inherited. As a result, close family members will often share some HLA and be better matched. With a deceased donor there is often not as much matching, but we will go ahead if that is the only option. If we waited for a well-matched deceased donor, it would result in a very long delay for a transplant and extended time on dialysis. Children have a higher risk for rejection than adults do. This is partly due to the fact that they have a stronger immune system that is at its peak in the late teenage years. If we look actively for rejection with screening biopsies, we find rejection in as many as 40% of children and youth in the first year after transplant. That is true even when people take all of their immune suppression medications on a regular schedule. Fortunately, if these rejection episodes are picked up early when they are mild, there is effective treatment. Your transplant team may also adjust the level of regular medication to prevent it from coming back after it has resolved. After the first year after transplant, the risk for rejection is less. It is more likely if there have been times where there is less protection from your transplant medications, like if the doses were reduced for side effects or infection, or if some doses of medications are being missed. Because most places don’t continue to do many screening biopsies after the first year, you will rely on regular monitoring of kidney function (blood creatinine) and drug levels to know if you should be worried about rejection. 

What lifestyle or dietary changes are needed after a kidney transplant in children?

Question from Annie (caregiver of transplant recipient)

Answer: The goal of doing a transplant is to improve your quality of life, especially compared o being on dialysis. The parent of one of my patients uses the expression “living your best life.” That is what we all want. In most cases, that means doing things that help your body to recover after a transplant and stay healthy. It includes eating healthy food, staying well hydrated, being physically active and taking care of your mental health and relationships. Most people have many fewer limitations after a transplant. Most transplant teams have a dietitian who can help with what foods are most healthy for you. The transplant team can also give you advice on where you can get advice on getting stronger (rehabilitation), being more active and what sports are safe to participate in. Social workers, psychologists and other people on the transplant team can help if you are worried about your mental health or that of your family members. Some people still need some adjustments, to deal with lower kidney function or other health issues. But the goal is to support you to go out and live your best life. 

What are the next phases to this study?

Question from Sarah (caregiver of transplant recipient)

Answer: This phase of the study will get us initial information on how we are able to best provide CXCL10 testing to young people living with a transplant. We will learn how often we detect important inflammation, how often that is due to rejection and how the transplant teams use the new test information in delivering care. The next phase will be a bigger study across Canada to see whether people who have regular urine CXCL10 testing do better over time – in terms of the kidney transplant health. This information is essential to prove that the extra cost of testing should be provided as part of standard care. Without funding from health insurance (i.e. provincial health funding), there is no way to include this testing as part of routine care.

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