Creating health equity
First Nations Peoples have one of the highest rates of chronic kidney disease (CKD) in the world. Diabetes accounts for about 75% of this disease. This rate of diabetic CKD is markedly higher than for non-Indigenous Australians.
Kim Morey, an Eastern Arrernte /Anmatyerre person, says First Nations Peoples are 'deeply concerned' about the burden of CKD in their communities. A lack of specialist medical services in rural and remote areas contributes to this burden.
'Elders often have to leave their homes and families to receive medical care, such as kidney dialysis,' Kim explains.
Kim is Co-Theme Leader of Wardliparingga Aboriginal Health Equity, South Australian Health and Medical Research Institute (SAHMRI). Kim is collaborating with Professor Mark Cooper, Monash University, a world expert in diabetic kidney disease.
They lead a research team using advanced multi-omics technology to detect, prevent and manage CKD in First Nations communities.
First Nations partnership
The CKD Study is the result of consultations with First Nations communities across South Australia. Kim carried these out with Alex Brown, now Program Leader of the Wardliparingga Aboriginal Health Equity research unit at SAHMRI.
The consultations highlighted the need to overcome the burden of diabetes and its complications to reduce health inequality.
Study co-design
'Communities tell us there are reasons for the high rates of diabetes and CKD,' Alex says. These are:
- high levels of stress
- intergenerational trauma
- a lack of equitable access to health services.
'Individuals from some families are more likely to develop CKD because of diabetes than what we see in other families. Communities want to know why and want to know what we are going to do about it.'
SAHMRI's PROPHECY program emerged from these conversations,' Alex recalls. The PROPHECY program:
- aims to understand why there are such high rates of diabetes related complications in First Nations communities
- investigates how diabetes operates in First Nations social and family environments. To do this, researchers measure environmental exposures, like exercise and diets, behaviours and psychosocial stresses
- works with health services to try to improve diabetes treatment and prevent CKD by predicting who will get these diseases into the future.
Starting at baseline
Kim and Alex started recording baseline information on diabetes and CKD in First Nations communities in 2015. 1,390 First Nations people gifted blood samples to the study.
The researchers used multi-omics to find biological markers in the blood samples. This baseline assessment created the world's largest and most complete genotype and phenotype data on First Nations Australians.
The PROPHECY CKD Study
With support from the MRFF, in 2022, the researchers started following up participants in a second wave of blood tests.
Researchers are identifying which markers they found at baseline occur in people who didn't have disease in 2015 but developed it over time.
They hope to find biomarkers that predict somebody is likely to develop CKD so that prevention can be better targeted.
The role of multi-omics technology
Multi-omics looks at multiple layers of detailed cell function. This research shows how a person's genes influence the chances of developing diseases like diabetes and kidney disease.
Multi-omics technology helps researchers study the pathway from our genotype (our unique genetic code) to our phenotype (our body's unique traits, including diseases).
Genomics studies the 'code of life', our DNA. Whilst the DNA in most people is very similar, everyone has small variations. Examining these differences in each person's genotype shows that some gene variations are associated with diseases. But having that gene is only the first step to getting the disease.
Before a gene is expressed as disease in our body, or phenotype, it must be 'switched on.' Specialised molecules transcribe the gene code into messenger RNA (mRNA) to transport it from the nucleus to the main body of the cell. Transcriptomics studies this process.
Other molecules then translate the mRNA code into amino acid code. This chains amino acids together to make proteins. The proteins structure, operate and regulate the body's tissues and organs, creating our phenotype. Proteomics studies these events.
How we live, and how other systems in the body work, can influence how proteins function. Metabolomics helps to 'read' how this occurs.
At each of these steps from our genotype to our phenotype, environmental factors influence how genes work. Epigenomics researches these environmental changes in gene function.
Causes of higher CKD rates for First Nations Peoples
Mark uses epigenomics to study how sugar and fat can change how genes behave.
'Our research group at Monash University was the first to show that sugar and fat can alter the genetic programming,' Mark says. 'We call this process DNA methylation.
'What happens is the methylated DNA modifies the proteins. Collagen is produced and deposited in the kidney. The collagen scars the kidney which damages it, causing CKD.
'Europid people who have CKD don't usually get it until 10 -20 years after they get diabetes. But many First Nations people get CKD just 2 - 5 years after getting diabetes,' Mark says.
During the PROPHECY CKD Study, Mark discovered that First Nations people with CKD have more advanced DNA methylation.
Predicting and preventing CKD in First Nations communities
Mark's research shows DNA methylation already occurs before people get CKD. That means high levels of DNA methylation could be a marker that predicts who will get CKD. Identifying this marker early could prevent CKD.
'If people have this marker, we can aggressively treat them early. We can say, we need to treat your blood pressure better. We need to keep your glucose down. We need to get you to lose weight.
'We are in a very exciting time because there are new drugs for CKD. We can give these drugs to people with DNA methylation before they get CKD. This could protect them from CKD,' Mark forecasts.
Benefit sharing
In the past, Australian scientists subjected First Nations Peoples to research without sharing the benefits of that research.
The CKD study shares research benefits with the participants. The study recognises participants own the blood samples they gift to the study. Participants grant the researchers a license to use the samples and data for the purposes of study.
Participants and their communities have a critical role in controlling how the research team generate and understand data from those samples.
The study team is talking to communities about how to manage intellectual property rights in research results. This includes new treatments derived from the data they own.
The PROPHECY CKD Study is supported by $2 million from the Medical Research Future Fund.
