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Sydney, April 24 – Researchers have identified a gene that controls the cut-off switch for kidney inflammation and could pave the way for more precise disease diagnostics and personalised treatment for kidney diseases.
The team from the Garvan Institute of Medical Research, University of New South Wales and Westmead Hospital in Australia, found that common genetic variants of TNFAIP3 — which increase inflammation in the body, can paradoxically protect the kidneys from damage in the short term.
“We wanted to investigate whether inherited differences in how people regulate inflammation could lead to better or worse kidney health outcomes,” said Professor Shane Grey, Head of the Transplant Immunology Lab at Garvan.
“We focused on the TNFAIP3 gene, which produces a protein called A20 that acts as a ‘brake’ on inflammation. Common variants of TNFAIP3 have been linked to autoimmune disease, but their role in kidney disease was unknown. Our discovery that some genetic variants can be protective against inflammation could lead to a simple genetic test that helps predict the risk of kidney disease for patients,” Grey added.
Acute kidney injury — a sudden and rapid decline in kidney function that is in part caused by inflammation — is an important risk factor for progression to chronic kidney disease. Currently there are limited treatment options for acute kidney injury, and imprecise tools to predict who is most at risk of poor recovery or kidney failure.
The team first investigated how different TNFAIP3 variants influence A20’s function, finding a series of rare variants that reduced its anti-inflammatory effect. They then tested the effects of one of the variants that promotes inflammation during kidney injury in a mouse model.
“Despite increasing inflammation, this rare variant surprisingly protected the kidneys from injury. We found this protection to be due to another of A20’s functions: preventing cells from self-destructing,” said Professor Natasha Rogers, nephrologist and Head of Transplantation at Westmead.
“Our study indicates that these ‘hot’ TNFAIP3 variants can alter the outcome of kidney injury, and they do so through complex effects on inflammation and cell survival.”
The study, published in the journal Kidney International, could lead to a simple genetic test to allow doctors to determine whether an individual carries a ‘hot’ version of the inflammation control gene, giving families greater certainty about their risk factors.
However, additional research is needed, the team said.