Nephrology
Research investigating children born with malformed kidneys
Overview
End-stage renal failure (ESRF) affects around 45,000 people in the UK which without life-long dialysis or a kidney transplant, would lead to death.
Most children with ESRF are born with malformed kidneys or have genetic disorders of tissue differentiation. Furthermore, at least 10 per cent of adults with ESRF have kidney disease which arose in childhood.
Our researchers have a track record in trials of immunosuppressive agents and drugs which treat proteinuria and high blood pressure associated with kidney disease.
Problem
About half of all children who need a kidney transplant or life-long renal dialysis, were born with kidneys which did not grow properly before birth. These children often have abnormally-shaped bladders and ureters as well.
These problems sometimes run in families, suggesting that they may be caused by a genetic problem.
What we aim to achieve
We aim to find out why these diseases occur in the first place, a question which is often long-sought by affected families.
Leaning more about why these conditions occur will allow us to explain the risks of recurrence within families, and begin to design novel therapies which may allow better kidneys growth and prevent kidney failure.
We have a programme of research which seeks to define the genetic bases of kidney and renal tract malformations. In addition, by better understanding which genes cause congenital disease, we learn more about the normal mechanisms of renal tract development, and this in turn suggests new treatment options, such as enhancing growth and differentiation by applying powerful growth factors.
What we have achieved to date
Our research into genetic bases of kidney and renal track malformations has had the following successes:-
The discovery that mutations of a gene called HNF1B are the commonest cause of kidney malformations in the context of Paediatric Nephrology clinics, and that a low plasma magnesium is a simple marker for this genetic condition. These advances are fed back to families by way of a renal genetic clinic.
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The establishment of a UK DNA Bank from 200 families affected by renal tract malformations, for use in genome-wide searches and other genetic strategies.
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The discovery of a new gene mutated in a bladder malformation syndrome. This codes for a protein which modulates angiogenesis and growth factor signalling, thus opening new perspectives for therapies.
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Engineering genetically-malformed renal tracts ex vivo, and rescuing then by application of growth factors such as GDNF.
