Decoding the Kidney

The Work of the Irish Kidney Gene Project (IKGP)

Dr. Susan Murray, Dr. Katie Benson, Prof. Peter J Conlon,

We have known for a long time that kidney disease runs in families. In fact, over a third of people in Ireland who develop kidney disease have at least one other family member affected by kidney disease. Diseases like polycystic kidney disease, which causes cysts on the kidney, or Alport syndrome, which causes deafness and kidney disease, are well known to occur in families of brothers and sisters, or be passed from parent to child. Though we have always seen the effects of inheritance in kidney disease it is only in the last few years that we have had the tools to comprehensively study and understand the causes of kidney disease at a genetic level.

The Irish Kidney Gene Project (IKGP) was set up in 2014 by Professor Peter Conlon at Beaumont Hospital and Prof Cavalleri, an expert gene scientist in the Royal College of Surgeons In Ireland. Prof Conlon has been involved in kidney gene studies for the last 25 years, since he started this work while studying abroad in Duke University in the USA, In Duke he helped discover new genes that caused kidney disease. Since his return to Ireland to work as a consultant in Beaumont Hospital in Dublin, he has continued this study of inherited kidney disease. A part of that work has been in founding the IKGP.

The IKGP is a national research study to try and understand what genes cause kidney disease in Ireland. It aims to identify individuals with kidney disease that may be inherited and genetic sequence those people to identify which genes are causing kidney diseases.

The IKGP has created a bio bank of DNA samples taken from patients with inherited kidney disease. It acts as a database of those affected by inherited kidney disease in Ireland, gathering clinical information and genetic data. It aims to unravel the causes of genetic kidney disease in Ireland, to help understand what genes are causing disease in the Irish population, to discover new genes in families affected by kidney disease and hopefully offer new diagnostic and treatment avenues, with the aim of improving care for patients with kidney disease all around Ireland.

To date, the IKGP has studied more than 1,000 patients Irish patients whose families have been affected by kidney disease, and have uncovered the underlying genetic causes of kidney disease for nearly half of these patients. The IKGP uses state of the art genomic medicine to test for genes that cause inherited kidney disease and collaborates with world experts in inherited kidney disease across the globe.

As part of the IKGP, we run a renal genetics clinic in Beaumont hospital twice a month. This clinic is for adults with known or suspected inherited kidney disease and helps to tackle the challenges unique to diagnosing and treating inherited kidney disease. We take referrals from all over the country and work with nephrologists in Cork, Galway, Limerick, Dublin and Waterford to help patients obtain a genetic diagnosis and counselling.    

Inherited kidney Disease clinic

The inherited kidney disease clinic:

• Takes place every second Friday morning in Beaumont Hospital
• Helps provide a genetic diagnosis for patients with inherited kidney disease
• Accepts referrals from nephrologists all over Ireland
• Employs state of the art genetic testing to unravel cause of kidney disease
• Collaborates with experts all over the world

Patients who come to our clinic will be reviewed by a consultant nephrologist and will be offered the opportunity to be tested for inherited kidney disease if appropriate. They will also be offered the opportunity to participate in research genetic studies. If disease causing genes are identified by these research studies they will be offered an opportunity to have a repeat blood test to confirm the result in a clinically validated lab. Any patients wanting to come to inherited kidney disease clinic must be referred by their own nephrologist.

Who should have genetic testing to identify cause of kidney disease?

• Patients who have a family history kidney disease where the gene is not known
• Patients who get kidney failure at a young age where the cause of kidney disease is not known
• Patients who present with possible polycystic kidney disease where there is no family history
• Potential live kidney donors where there is a possibility that they could have kidney disease also
• Patients who have kidney disease and other symptoms where the two may be related

The IKGP is a research project and it relies on the generosity of those who are willing to donate blood and DNA samples to the biobank for study, as well as their time to answer questions about their family history. The IKGP may also sometimes ask patients whether a parent, sibling or other relative not affected by kidney disease would donate a DNA sample. If the patient and the family member agree, this can help us to decode the affected patient’s DNA and potentially identify the cause of their inherited kidney disease.

Why Genetic Testing?

One of the big advantages of understanding inherited kidney disease and identifying the genes that cause it is in helping to make a diagnosis. As most people reading this will know, kidney disease is often silent until very late in the disease and there may not be any outward sign of kidney disease until it is very far advanced. In up to 20 per cent of patients the cause of kidney disease is unknown. Genetic testing helps us to identify kidney disease before there are outward signs, and sometimes even before there are signs on blood tests or on imaging. It can be helpful in screening family members, and also in advising patients of the risk of passing on their kidney disease to their children.

Genetic testing can help tell us how a disease is going to behave in the future. For example, there are two major genes that cause polycystic kidney disease. One, PKD1, causes more severe disease, while a second; PKD2 causes much milder disease that may never progress to needing dialysis or kidney transplantation. Similarly, genetic testing can give us information about how a disease is going to behave after kidney transplantation and whether the disease that caused renal failure in the first place can come back.

Genetic testing may also help us in patients who need renal transplantation. Every year, dozens of people in Ireland give the gift of a kidney to a friend or relative. Our priority is to ensure that this process is safe both for the recipient and the donor, and that we avoid causing any harm to the donor. We do a number of tests on the donor to make sure it is safe for them to donate their kidney. If we know the cause of kidney disease in the recipient, we can test for this gene in the donor, particularly if they are a blood relative. This gives an added layer of security when ensuring it is safe to go ahead with a transplant.

Recent Projects of Irish Kidney Gene Project

• Survey of almost 2,000 kidney patients across the country identified that 27% of patients had a family history of kidney disease suggesting a underling genetic cause.
• Analysis of 130 Irish families using state of the art genetic sequencing technology identified a genetic diagnosis in 33% of cases
• Analysis of Irish families with kidney disease demonstrates that 0.5% carry a diagnosis of autosomal dominant tubulointerstitial kidney disease.
• Analysis of Irish patients with polycystic kidney disease using state of the art gene sequencing technology identified the underling gene cause in 85% of cases.
• Beaumont hospital renal unit started a clinical trial of new “smart” medicines to slow progress of specific types of kidney disease.
• Beaumont Hospital renal unit published seminal papers identifying the role of genes in outcomes of kidney transplants and development of cancer after transplantation.
• Irish Kidney gene project sponsors international al symposium on inherited kidney disease

The IKGP will continue to work both in Ireland and abroad to better understand kidney disease in Ireland and to improve care for those with kidney disease.

Attendees at the second Irish Renal Genetics Symposium, November 2019