Prof. Richard MacIsaac: Novel biomarkers predict renal decline in T2D

Type 2 diabetes

By Siobhan Calafiore

8 Nov 2023

Professor Richard MacIsaac

Novel biomarkers may play an independent role in kidney disease progression in type 2 diabetes and could help identify those at risk, an endocrinologist says.

Speaking at a seminar at the Australian Centre for Accelerating Diabetes Innovations (ACADI), Professor Richard MacIsaac said type 2 diabetes was the leading cause as to why people entered into renal replacement therapy.

And while Victorian data suggested rates of end stage renal disease were declining, rates for dialysis and kidney transplantation remained “relatively flat”.

Professor MacIsaac said while newer agents like SGLT2 inhibitors and GLP-1 receptor agonists might help decrease renal complications, he was investigating whether biomarkers could identify those at highest risk of progressive disease.

“What we’re trying to do in this space is to identify people early… with the idea of intervening early with appropriate therapies. Possibly these changes in biomarkers will give us an idea regarding different pathways to target and so new treatments might develop,” said Professor MacIsaac from the University of Melbourne.

He said these pathways might include low grade inflammation, heart disease and the relationship between injury to the renal tubules and diabetic neuropathy.

Professor MacIsaac cited a study involving more than 400 Indigenous Australians with and without diabetes in five locations across northern and western Australia, where measurements were taken for soluble tumour necrosis factor (TNF) receptor 1, high-sensitive troponin T (hs-TNT) and kidney injury molecule-1 (KIM-1).

“Interestingly, in people without diabetes, we didn’t find a significant relationship between TNF receptor levels at baseline and changes in GFR over time, but in people with diabetes, higher levels of TNF receptor were associated with a greater decline in GFR over time,” Professor MacIsaac told the seminar on 20 October.

“We’re also able to show that a doubling of the level of the receptor for TNF at baseline was associated with a significantly increased risk for developing the renal endpoint of a greater than or equal to 30% decline in GFR into a GFR below 60, renal replacement therapy or renal death.”

They also looked at hs-TNT, identifying that the highest levels of troponin T were associated with lowest GFR values at baseline and highest levels of albuminuria.

Further, for people with diabetes, increasing troponin levels were associated with a graded increase in kidney function decline over time after adjustment for age, sex and albumin levels, whereas there was no relationship for those without diabetes.

For KIM-1, there was no significant relationship between baseline markers and renal function decline in people without diabetes, but a “hint” of a relationship for those with diabetes, with greater declines associated with higher levels of KIM-1.

Professor MacIsaac said adding these markers to a model designed to help determine the risk of patients developing progressive renal function loss, they were able to increase its predictive power up to 24% from a previous model based on traditional risk factors such as age, sex, EGFR and urinary albumin at baseline.

“Maybe there is something there in terms of helping us to find high-risk patients, but also something there in terms of helping us to identify pathways that we might potentially be able to target in the future to slow down renal function loss,” he said.

But, he added: “We still don’t know whether preservation of renal function is modifiable through prevention of causes of chronic inflammation, myocardial damage or urinary tubular injury. This is an area for further research.”

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