In the UK, there are 3,000-5,000 people who were born with abnormal kidneys and/or bladders who have such severe kidney failure that they can only survive by having regular dialysis or kidney transplants.
The UFS is a specific disease in which urinary bladder muscle does not behave normally. The condition starts before birth and people with the disease suffer life-long urinary incontinence and have a high risk of developing kidney failure. There is increasing evidence that such individuals carry abnormalities of genes which normally drive the growth and development of the bladder and kidney before birth. Finding the specific genetic causes of such disorders provides families with often long-sought answers to the question “why was our child born with kidney disease?”
We were the first to describe changes in two genes responsible for this disease. Affected children inherit two copies of an altered gene, one from each parent, who themselves are healthy. We believe that the normal function of these genes is to help the growth of nerves into the bladder and that these nerves control the filling and emptying of the bladder. This research project, led by Professor Adrian Woolf and funded by the Medical Research Council, will search for other genes which cause the UFS and related conditions. These include ‘primary vesicoureteric reflux’, the backwards movement of urine from bladder to kidney, a condition which affects around 1 in 100 of all babies.
To understand why these diseases occur, and what the genes do, experimental models of the human condition will be studied. By identifying the genes responsible for UFS, it will be possible to identify carriers within affected families and so inform reproductive choices including pre-implantation or prenatal diagnosis for this potentially devastating disorder. Current clinical interventions for congenital bladder disorders, such as surgery to refashion the renal tract and fetal termination, do not target the primary causes of disease; novel treatments will be tested in these models with the aim of using similar treatments in the future to treat people with bladder disease.