One in three people with diabetes could be helped by the discovery of researchers working in UCD. Claire O'Connell reports
When it comes to genes sometimes it's not what you've got, but when you use it.
UCD researchers have found that a kidney development gene which usually stays silent in adults gets switched back on in diabetic kidney disease.
Their discovery could lead to new therapies for the one in three people with diabetes who develop kidney complications.
In diabetes, the body's usual regulation of sugar levels in the blood is disrupted. Over time, resulting high blood-sugar levels may lead to cardiovascular, nerve, eye and kidney problems.
An estimated 200,000 people here have diabetes, according to the Diabetes Federation of Ireland (DFI), and a further 200,000 live with the condition but are as yet undiagnosed.
"The really huge economic burden of diabetes actually relates to the complications," says Prof Catherine Godson, who has been looking at the genetics of diabetic kidney disease for the past seven years at University College Dublin's Conway Institute. "We currently spend around 10 per cent of our healthcare budget treating diabetes and its complications, and that figure is set to rise as the number of people with diabetes increases," she says.
Around a third of people with diabetes will develop diabetic kidney disease where cells thicken, the kidney progressively loses the ability to filter waste products, and the organ ultimately fails if the disease advances far enough.
Around 400 people in Ireland have kidney failure as a result of diabetes, according to Dr Peter Conlon, a consultant nephrologist at Dublin's Beaumont Hospital.
Currently the only cure for diabetic kidney disease is transplant, but drug therapies, dietary restrictions and, at a later stage, dialysis can help to manage the condition.
The presence of a protein called albumin in the urine is an early indication of diabetic kidney disease, says Conlon.
People with diabetes are screened for the early stages of the disease as part of their annual check-up and receive protective drugs to help ward off kidney problems, according to nurse specialist Anna Clarke, health promotion officer with DFI. "Yet 35 per cent go on to develop diabetic kidney disease," she says.
The World Health Organisation predicts that by 2025, 300 million people worldwide will be living with diabetes. With the epidemic escalating, the drive is on to find ways of identifying persons with diabetes who are likely to develop kidney disease, and to design new drugs to treat kidney problems when they do arise.
To this end, a group of scientists and medical researchers led by Godson and professors Finian Martin and Hugh Brady looked at genetic events underlying diabetic kidney disease.
The team took the type of kidney cell that is most affected by the condition and grew cultures in the lab. When they grew the cells in high glucose - which mimics the stress of diabetes - the scientists saw that certain genes were switched on. One of these was "gremlin", a gene involved in embryonic kidney development in animals.
Together with international collaborators they went on to show that gremlin, which is normally silent in the adult kidney, turns on again in diabetic kidney disease in amounts that relate to the severity of the condition.
"We know that we need that gremlin, that it's an important gene for kidney development, but that in the adult it drives a disease state, which is an interesting paradigm," says Godson.
"We think that in diabetes gremlin interferes with the body's protective mechanisms and exacerbates the response to injury," she says.
Their discovery creates a potential new opportunity for treating diabetic kidney disease. Gremlin impinges on a protective cellular pathway in the kidney that is already under investigation for new drug therapies, says Martin.
On the basis of their research, gremlin could represent a new drug target for kidney disease, and they plan to investigate its biochemical role further over coming months.
For more information on diabetes or diabetic kidney disease, contact the Diabetes Federation of Ireland helpline at 1850 909 909 or see the website www.diabetesireland.ie