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John Sayer is a Clinical Professor of Renal Medicine, Newcastle University, UK, and runs the Renal Genetics Service and Family Renal Genetic clinic at Newcastle Upon Tyne Hospitals NHS Foundation Trust. He published a case report, including both the clinical and patient perspectives, to think about the consequences of analysing genes to discover the underlying cause of disease, and the impact such a genetic diagnosis has on the patient and their family.

Familial renal disease

Familial or inherited renal diseases are a group of rare diseases that lead to loss of kidney function, often requiring kidney dialysis or kidney transplantation. They are in the main, severe conditions that run in families and cause devastating emotional, psychological and physical consequences. If the condition is inherited in an autosomal dominant fashion this means that each generation of a family could be affected, with the risks of passing the condition on 50% for each child.

This means that in large families, multiple people will be affected, with the older generations feeling guilty that they have handed down a medical condition in their genes and the younger generation living in fear of developing the condition that they have witnessed in their parents, aunts and uncles and grandparents. For younger family members, the feeling of either sitting on a time-bomb or feelings of denial and avoidance of health care providers is a very common scenario.

Grouped together, inherited kidney conditions probably explain around 20% of all cases of kidney failure. The most common inherited kidney condition worldwide is Autosomal Dominant Polycystic Kidney Disease (PKD), and patient forums and advice via the PKD Charity provide enormous support for these families. Rarer forms of familial renal disease exist and the importance of patients and their families sharing their experience is invaluable. The Renal Association UK has set up a rare renal diseases hub called RaDaR to facilitate this – Registry (RaDaR) | Rare Renal.

Finding the gene

It may sound trivial, but for many patients and their families, having a precise diagnosis performed using DNA analysis to discover the underlying change in the gene is absolutely fundamental. The benefits to such a genetic diagnosis allows the precise disease to be categorised, to avoid repeated investigations, (which are often invasive and costly), to make plans regarding possible treatments (including renal transplants), and to allow other family members at risk of the disease to be tested.

Some genetic diseases which affect the kidney come straight back again in the transplanted kidney, and therefore it is vital that these conditions are diagnosed well in advance of a kidney transplant operation to avoid risks to both the donor and the patient.

The patient journey

Most inherited kidney conditions are severe. Therefore the diagnostic odyssey will involve medical tests, interventions and treatments alongside genetic studies, which can take many years to undertake. Engaging the patient and their family members in this process allows the patient to gain ownership of their plight and for the doctor to be less paternalistic and more a co-investigator of the family’s genetic problem.

The belief that expending the effort to perform large numbers of genetic tests (which are costly and can take a long time) for a precise diagnosis must be shared between the doctor and the patient.  Preparedness for the genetic results (whatever they may be) must take place long before any blood samples are taken.

A patient perspective

We all have different views on life! In clinical medicine it is my belief that time should be taken to step back from the sharp edge of making all the decisions and reason with the patient about what their understanding and wishes are. This should go without saying, but historically doctors have been trained to “do the right thing” and make decisions on the patient’s behalf or best interest.

The huge advances in genetics and genomics, which include The 100,000 Genomes Project, allows us to enter a dialogue about the mystery of our genetic make-up and the consequences of analysing genes to discover the underlying cause of disease. The patient perspective nearly always brings new and informative information to the table and can be a time to dispel myths and prejudices too.

Ethical dilemmas

Of course, for many families, the finding of a gene defect underlying their disease is a double edged sword. The new genetic information can be used for beneficial things such as treatment decisions and planning for the future, but simultaneously begs the question regarding testing other family members at risk of inheriting the same problem.

The argument in favour of finding out whether a child is affected must be balanced against the downside. Making a genetic diagnosis before any symptoms appear does remove a child’s right to choose and may cause them distress growing up. However, there may be preventative measures and new treatments for the disease that may be most effective in its earlier stages. Much guidance and support regarding genetic testing of rare conditions can be found through the Genetic Alliance UK.