Genetic test can identify patients most at risk of kidney rejection

When Frances Zammit was 27, her kidneys failed. For seven years she required dialysis three times a week until in 2008 she received a kidney transplant.

The donated organ never worked properly and nine months later it was removed. She was back on dialysis and waited another six years until she could receive another kidney.

That came in December. The kidney has good function but it is already showing signs of fibrosis, a worrying indicator that it, too, might fail.

But there is hope a new genetic test will be able to catch early signs of transplant difficulties.

Frances Zammit last year on her home dialysis machine while she was waiting for her second kidney transplant, which she ...
Frances Zammit last year on her home dialysis machine while she was waiting for her second kidney transplant, which she received in December. Photo: James Brickwood

Researchers at Sydney’s Westmead Institute have identified 13 genes that can predict the development of kidney fibrosis within three months of transplantation.

The lead author in a study published today in The LancetProfessor Philip O’Connell, said: “Identifying who is at risk [of rejection] and what to do about it has been a challenge.”

Professor O’Connell is director of the Centre for Transplant and Renal Research at Westmead.

Currently, the only way to identify chronic injury in transplanted kidneys is by conducting biopsies after the implant. By this stage, irreversible fibrosis of the organ has usually occurred. 

Professor Philip O'Connell expects clinical use of the genetic test in about five years.
Professor Philip O’Connell expects clinical use of the genetic test in about five years. Photo: Westmead Institute

By testing for the genetic markers within three months of surgery, Professor O’Connell said that alternate treatments for patients could be developed before damage occurs.

He is hopeful of developing the genetic test for clinical use.

“Early risk detection would mean we can try different strategies to support the graft at a time when we can make a difference,” he said.

Such early intervention would make all the difference for a patient like Ms Zammit. She said that the less change in treatment there is through your transplant journey, the better your daily routine is, which is much better for your state of mind.

“If you can eliminate as much worry as you can early on, it helps you know that you are in good hands,” she said.

Professor O’Connell said: “We are probably about five years away from using this tool in a routine clinical setting.

“Our next step is to undertake clinical trials to see what treatments will help.”

Professor O’Connell said: “We are hoping this will lead to increased kidney graft survival over the long term. This would mean less mortality, fewer people returning to dialysis and people having a better quality of life.”

It is unclear which methods will work best. It could be a case of tailoring treatments for individual patients.

“Patients might need better anti-rejection treatments. But this puts them at risk of more opportunistic infections or cancers,” Professor O’Connell said.

“Or we could use drugs that prevent fibrosis and therefore we wouldn’t need more aggressive suppression of the immune system. This might end up being safer for people.”

If Ms Zammit’s kidney should fail and she requires another transplant, future treatments might be available to allow for early intervention to help support the transplant. 

“You’d have so much better peace of mind from catching problems early on and acting on them,” she said.

Kidney transplants are the most common solid organ transplant operations in Australia. Kidney-related disease kills more people each year than breast or prostate cancer.

In 2015 nearly 1000 Australians received a donor kidney.

At the end of 2014 there were more than 10,000 Australians living with a functional kidney transplant. As of February 1 this year, 1083 people were on the waiting list for a kidney transplant.

Professor O’Connell’s six-year study was jointly conducted by researchers at the Westmead Institute for Medical Research and Mount Sinai Medical School in New York.