Inflammation Genes May Predict Kidney Disease Outcomes

(CTN News) – An investigation of gene variants of an Inflammation brake brings scientists one step closer to developing personalised treatments for patients at risk of kidney disease and kidney failure.

In a study at the Garvan Institute of Medical Research, University of New South Wales in Sydney, and Westmead Hospital, researchers found that common genetic variants of TNFAIP3, which increase inflammation in the body, paradoxically protect the kidneys from damage in the short term.

The research was conducted by Professor Shane Grey, senior author and Head of the Transplant Immunology Lab at Garvan, to determine whether inherited differences in how people regulate inflammation could result in better or worse kidney health outcomes.

Our study focused on the TNFAIP3 gene, which produces a protein known as A20 that acts as a ‘brake’ on inflammation.

There has been a link between TNFAIP3 variants and autoimmune diseases, but it has not been established whether these variants are also involved in kidney disease.

A simple genetic test that helps predict the risk of kidney disease for patients may be developed as a result of our discovery that some genetic variants can be protective against inflammation.”

Pro-inflammatory variants exhibit unexpected protective effects

Inflammation plays an important role in chronic kidney disease, a major health problem that affects approximately one out of ten Australians.

Acute kidney injury is a sudden and rapid decline in kidney function caused by inflammation.

Acute kidney injury currently has limited treatment options, and it is difficult to predict who is most likely to suffer poor recovery or kidney failure.

A20’s anti-inflammatory effect was reduced by several rare variants of the TNFAIP3 gene identified by the team. In a mouse model, one of the variants that promote inflammation during kidney injury was tested.

Although this rare variant increased inflammation, it was surprising to find that it provided protection for the kidneys. This protection appears to be a result of A20’s ability to prevent cells from self-destructing, according to Professor Natasha Rogers, nephrologist at Westmead Hospital.

The results of our study indicate that these ‘hot’ TNFAIP3 variants can alter the outcome of kidney injury through complex effects on inflammation and cell survival.”

Kidney International published the findings of this study.

Treatment approaches that are on the horizon

According to Professor Grey, more research is needed, but these findings bring us closer to predicting who is at risk of poor kidney recovery and opening up the possibility of personalised treatment.

There may be a simple genetic test available soon that will allow doctors to determine whether an individual is carrying a ‘hot’ version of the inflammation control gene, giving families a greater sense of certainty about their risk factors.

This research contributes to the development of precision diagnostics and tailored treatments for acute kidney injury by providing insight into how variants in the TNFAIP3 gene influence kidney function, according to Professor Grey.

We may be able to determine the best way to monitor a patient’s condition according to their variant of TNFAIP3, and tailor interventions in order to boost kidney recovery and long-term health.

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