New diagnostic test for PKD − another example of WGS changing medicine

An advanced research test for polycystic kidney disease (PKD), developed at the Garvan Institute of Medical Research, has been translated through Genome.One into the world’s first clinically accredited diagnostic whole genome sequencing (WGS) test for PKD.

Dr Nicole Schonrock, Medical Science Liaison at Genome.One, discusses the exciting new test which is changing the diagnosis of PKD.

“Polycystic kidney disease (PKD) is an inherited condition in which many fluid filled sacs, also called cysts, form in the kidneys. It’s a progressive disorder that gets worse over time as the cysts grow and kidney function declines, and unfortunately, it often causes kidney failure. Autosomal dominant PKD (ADPKD) is the most common form, which is mostly caused by mistakes in two genes called PKD1 and PKD2. Genetic testing for ADPKD is challenging as there are six other genes present in our DNA with an almost identical sequence to PKD1 making it hard to identify the real gene. Traditionally PKD is diagnosed using imaging techniques. A diagnostic genetic test for ADPKD using long-range PCR is available in the UK to sequence PKD1 but this technique cannot look at all types of genetic changes.

“The new PKD test, which is now available in Australia but is not currently available on the Medicare Benefits Schedule (MBS), allows us to diagnose PKD using whole genome sequencing. The patient’s entire DNA is sequenced and a group of nine genes that are known to cause large kidney cysts in adult and paediatric patients are analysed. The new test looks at all types of genetic changes in these genes and the individual’s entire genetic information then becomes a lifelong resource to use and re-analyse as needed. For example, this information can provide insights into pharmacogenomics and the patient’s response to certain medications, which is information that their doctors could use to guide prescriptions and avoid possible adverse side effects.

“My role in making this test available was as a Medical Science Liaison at Genome.One. I’ve been working with research, commercial and clinical teams to increase knowledge and awareness and drive translation of the research into a clinically accredited test that is now available to the renal genetics community.

“This test offers benefits to both the patients and their families. For patients, it can help confirm the diagnosis or discover the exact cause of disease if the clinical diagnosis is unclear. It allows clinicians to make more informed decisions and, in certain circumstances, could avoid further, more invasive tests such as kidney biopsies. It can also help an individual to know what to expect. For instance, certain genetic changes in PKD1 are often associated with a more severe and early onset form of the condition, compared with variants in PKD2. Although there is currently no cure for PKD, early detection and management may reduce some of the symptoms and help maintain kidney function. This might take the form of treating hypertension and proteinuria, or implementing lifestyle changes such as drinking more water. The individual’s family may also benefit from genetic testing if the results lead to screening of at-risk family members. This can be useful to see if an individual could be a kidney donor. If you are a family member who wants to donate a kidney, clinicians need to be absolutely sure that you don’t have the condition. If the individual is a young donor, that might not be possible to determine using imaging technologies but is possible using genomic information. Individuals with PKD and their relatives might use genetic testing results to assist with family planning.”

“The test has now been available in the clinic for approximately 12 months. Since then, we have had nearly 80 families come through Genome.One and there were many more involved in the validation process to get the test set up. We are also working closely with PKD Australia, around creating awareness for patients so that they can be partners in the decision making process about their health. A major challenge is that the availability of tests often runs ahead of funding schemes and health providers’ awareness.”

“The test is accessible from genetics clinics. Kidgen, the renal flagship of the Australian Genomics Health Alliance, has been driving the establishment of fifteen renal genetics clinics across the country, and this number is growing. With nephrologists, clinical geneticists and genetic counsellors working together they understand adult and paediatric renal genetics exceptionally well and are very well placed to help families access this test.”

“From my perspective, genetic testing should be another tool in a clinician’s suite of tests to help diagnose, manage and effectively treat their patients. It complements current testing and provides additional insights not given by other technologies. Genomic testing has the ability to change medicine from a reactive to a proactive way of dealing with health. However, many challenges still remain in dealing with cost, accessibility and integration into routine medical practice. Genomic testing will impact the health system in a big way and ADPKD is just a beautiful example of a condition that can be diagnosed using this advanced technology.”

This article appeared in the May 2018 Edition of ePathWay which is an online magazine produced by the Royal College of Pathologists of Australasia:

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