January 31, 2024  Print

A groundbreaking research project, led by WIMR Executive Director, Professor Philip O’Connell, has been awarded a Medical Research Future Fund (MRFF) Genomics Health Futures Mission grant of $2,474,439 over four years.

The Genomics Health Futures Mission is investing $500.1 million in genomic research. It will improve testing and diagnosis for many diseases, help personalise treatment options to better target and improve health outcomes and reduce unnecessary interventions and health costs.

This WIMR-led project aims to develop and validate a risk score for kidney transplantation. Incorporated at the time of transplantation, the risk score could identify patients at risk of acute rejection (AR) and long-term graft loss.

Professor O’Connell, who is also Director of WIMR’s Centre for Transplant and Renal Research, says that a risk score is a much-needed clinical decision-making tool that could improve transplant outcomes for kidney transplant patients globally.

Kidney disease in Australia and globally
Around 10% of the global population is impacted by chronic kidney disease (CKD), and this figure is rising.  It is the ninth most common cause of death, with the number of people receiving renal replacement therapy – including transplantation – exceeding 2.5 million and expected to double to 5.4 million by 2030.  In Australia, approximately 10% of the adult population have CKD.

Kidney transplantation remains the optimal treatment for suitable patients with kidney failure because it affords significant survival and quality of life advantages. The average total life years gained for patients treated with transplantation, compared to dialysis, is 20 years, accompanied by an increment in quality-of-life score from 0.65 to 0.87 (a score of 1 being perfect health), within 12 months after transplantation. This fact is not lost on Australian patients, who in surveys have indicated that death is preferable to a return to dialysis.

As in other parts of the Western world, the short-term results for kidney transplantation in Australia are very successful, with one-year graft survival of 94%. However long-term outcomes beyond the first year have changed very little over the past 30 years. On average, the 5-year survival for primary renal grafts is 82%, 75% survive 10 years and more than 50% of grafts are lost by 16 years after transplantation.
Professor O’Connell says, “These results have changed little over the past 25 years and improving graft outcomes is one of the major unmet needs of transplantation. One of the major challenges, is the lack of predictive tools that could be used early in the course of the transplant that would identify patients at risk of graft loss.”
The need for a kidney transplant risk score
To determine how genetic variation outside human leukocyte antigen (a molecule involved in the induction, regulation of immune responses and the selection of the T cells) impacts kidney transplant survival. By screening donor and recipient pairs from a large patient cohort, the research team will identify genetic mismatches to produce a risk score associated with graft loss.

Professor O’Connell says, “We will use large multi-ethnic data bases to measure the impact of ethnicity on risk frequency, for example, gene mutation, and merge this data with existing data to develop an assay that will better inform clinical decision making.

“This project is a wonderful example of WIMR’s focus on precision medicine – using detailed analysis of the specific characteristics of an individual’s disease, along with the individual’s unique genetic profile, to develop a treatment regime that holds the most promise for best health outcomes.

“Precision medicine is a revolution in patient care, and WIMR is proud to be at the forefront of precision medicine in Australia.

“We are delighted that this project has been awarded this MRFF Genomics Health Futures Mission grant, accelerating our research findings into clinical practice that will change and save lives.”