Chief Investigator:

Paul Henning

Funding Amount:

$70,000

Recipient:

Women’s and Children’s Health Network

Overview:

Renal transplantation is the optimum treatment for children with kidney failure. Unfortunately transplant requires lifelong immune system suppression, and hence, the risk of life-threatening infections and cancer. Reducing immunosuppression to avoid these outcomes may result in kidney rejection and transplant loss. This research will explore a number of innovative immune system markers permitting fine-tuning of immune suppression treatment, such that the fine balance between over- and under-immunosuppression can be achieved, and survival of children with renal failure can be maximised.

Research Outcomes:

Researchers:

Paul Henning, Robert Carroll, Sam Crafter

Research Completed:

2019

Research Findings:

This project was to determine if a urine level of an inflammatory marker could predict those children at risk of having rejection before blood values of kidney function changed. The project also determined whether level of antibody to blood vessels was an issue for paediatric transplant patients.

Levels of the inflammatory marker did rise in the urine of patients with rejection and a negative result means the kidney will do well long term. Levels of the antibody do occur at higher levels than the adult population. These antibodies were associated with antibody mediated rejection and kidney thrombosis in children.

As a result of this study, collaboration with another unit in Winnipeg, Canada has occurred and the urine test is going to be commercialised so that testing can occur as part of routine care. The antibody to blood vessels is now becoming routine of care for all paediatric kidney transplant patients nationally.

Key Outcomes:

Urinary inflammatory markers to predict kidney transplant rejection in children with a kidney transplant.  Levels of antibodies to blood vessels in children with a kidney transplant and risk of rejection.

In this study we assessed the levels of these two factors in (n=57) children with kidney transplants from Westmead, Sydney Children’s’ Hospital and Women’s and Children’s Hospital Adelaide.

In those children with stable kidney function and no history of rejection, the levels of CXCL-10 were undetectable. In those with a history of rejection and non stable function, the levels were variable but usually positive. Only those patients with the highest quartile of urinary cytokine values however had significant drops in their kidney function over the next 12-24 months.

The Adelaide lab that tested these levels is now being involved in the commercialisation of the test.

For assessment of antibodies to blood vessels and the risk of rejection, kidney thrombosis and or hypertension, the levels of these antibodies were elevated compared to those kidney transplant patients without these issues.

Compared to adult patients, the levels of these antibodies are higher in children with a transplant.

To prevent graft thrombosis and early rejection and hypertension, the Adelaide Group now performs pre-emptive treatment of these antibodies and has not experienced early rejection or thrombosis since 2015. This experience is to be published in the journal Human Immunology- accepted March 2019.

The Westmead and Sydney Children’s Hospitals are now pre-emptively treating these antibodies. There have also been rejection episodes where the management has completely changed as a result of testing these antibodies as part of this project.

After the cessation of the project the following outcomes have occurred – and or are in the process of change.

All children with a transplant are being screened for these antibodies at the three hospitals involved in the project. If these antibodies are found and children have high blood pressure, they are having their blood pressure tablets changed to a class of drug called sartans – which are known to block the antibodies effects.

In children where there is evidence of a certain type of rejection, these children are now being treated with plasma exchange rather than just steroid alone. In this respect it has changed clinical practice.

Research Papers:

IN PRESS:

Proactive treatment of Angiotensin Receptor Antibodies in Kidney Transplantation with Plasma Exchange and/or Candesartan is safe and associated with excellent graft survival at 4 years: a single centre Australian experience. Accepted March 2019 Human Immunology in preparation; CXCL-10 in stable adult and paediatric renal transplant populations and multicentre study

CONFERENCE PRESENTATIONS ARISING FROM THIS RESEARCH PROJECT:

TSANZ Plenary Presentation 2017 – Angiotensin Receptor Antibodies in Paediatric and Adult Populations

2018 European Society of Transplantation – poster presentation: Screening for Urinary Chemokines in Long Term Renal Transplant Patients Associates with Cellular Rejection, Microvascular Damage and Falls in GFR Over Time. G Irish, M Hockley, S Kireta, J Johnson, R Carroll

Transplantation 102, S477 2018

2018 American Transplant Congress- poster presentation: Urinary Chemokine CXCL-10 in Long Term Renal Transplant Patients Associates with Urinary Tract Infections and Microvascular Damage. G Irish, M Hockley, S Kireta, J Johnson, R Carroll

AMERICAN JOURNAL OF TRANSPLANTATION 18, 516-516: Asia Pacific Histocompatibility and Immunogenetic Conference Sydney November 2018 – Angiotensin Receptor Antibodies Review of National Testing Reference Centre

Related Publications:

Future Outcomes:

As a result of this study, collaboration with another unit in Winnipeg, Canada has occurred and the urine test is going to be commercialised so that testing can occur as part of routine care. The antibody to blood vessels is now becoming routine of care for all paediatric kidney transplant patients nationally.

Remarks:

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