Meet the Experts: Navigating Kidneys and Genes

At the 61st European Renal Association (ERA) annual meeting, held from 26-28 May 2024 in Stockholm, Medicom sat down with two prominent figures in the field of nephrology, Prof. John Sayer (JS) from Newcastle University, UK, and Prof. Roman-Ulrich Müller (RM) from University Clinic Cologne, Germany. Both experts shared their perspectives on the evolving landscape of nephrology, particularly the significant role of genetics in diagnosing and treating kidney diseases.

Sources: www.researchgate.net; www.cecad.uni-koeln.de

Thank you both for being here. What role does the ERA play in forming our young nephrologists?

JS: "I came here to the ERA many years ago, when it was in Stockholm in 1998 or 1999. I saw an inspirational speaker at that meeting when I was a very junior researcher. The speaker's name was Friedhelm Hildebrandt. He gave an amazing plenary talk about genes, the kidney, and inherited kidney disease. This was the first time I was blown away by the depth of knowledge and the potential of emerging technologies for sequencing genes. Inspired by that talk, I contacted Friedhelm later on and ended up working in his lab in Michigan. He's now at Harvard, but that event was pivotal in my career."

That's a great example. Prof. Müller, how has the ERA impacted your career? You're quite involved in the organisation itself, right?

RM: "I work with the ERA specifically on genetic kidney disease, together with John, in the 'Working Group Genes and Kidney'. It used to be called the 'Working Group on Inherited Kidney Disorders', but we felt it needed a shorter, nicer name. This group is essential for my work, allowing for networking and collaboration on this important topic. We all share the idea that while genetic kidney disease was once thought rare, it explains a large proportion of chronic kidney disease. This requires advocacy, work, and guidance in the field."

Could you both elaborate on how the ERA currently helps shape the new generation of nephrologists?

RM: "The ERA provides a perfect platform for networking and finding mentors. This is strongly advocated by the ERA and is a significant part of the Young Nephrologists' Platform (YNP). This platform helps young nephrologists get active and be heard. In our working group, YNP members can join as observers, learning and interacting with experienced professionals. There are also funding tools like fellowships that allow for international exchange. For example, my lab was awarded a fellowship, and we'll have a young colleague from Mongolia joining us later this year. This facilitates knowledge sharing and expertise development."

JS: "I'd add that the leadership at the ERA is evolving with a focus on genetics and rare diseases. I just came from a pre-meeting on rare diseases where the current and incoming presidents were both present. This top-down signal that rare diseases are important for all nephrologists is crucial. Albert Ong, who chaired this meeting's organising committee, is interested in cystic kidney disease and rare diseases, so this focus is permeating the entire culture, which is exciting."

Great segue into our next topic: rare diseases. You both focus on genetic diseases in adults. Isn't this typically the domain of paediatric nephrologists?

RM: "It used to be, and that's a common misconception. Genetic diseases are often identified in childhood due to early onset. However, we now see these same diseases presenting later in adults. Twenty years ago, people thought genetic testing in adult kidney disease was irrelevant, especially without a family history. This has completely changed. It's now understood that genetic causes of kidney disease are common in adults. The ERA plays a vital role in spreading this knowledge."

John, you're presenting on NPHP1 loss in adult-onset disease, right?

JS: "Yes, we've learned to identify inherited diseases in children, but we're now seeing the same phenotypes in adults. In my work, we've found that many adults with undiagnosed kidney disease had deletions in NPHP1, explaining their symptoms, including extra-renal manifestations like retinal degeneration. Genetics helps optimise patient care by addressing the whole patient."

When should a doctor refer a patient to a geneticist?

JS: "It depends on the country. Nephrologists need a basic understanding of genetics because it permeates all disease spectrums. In my unit, we involve clinical genetics early for diagnosis, management plans, and cascade screening of families. It's crucial to work with clinical genetic colleagues from the start."

Prof. Müller, is your experience similar?

RM: "Yes, and it's becoming more important. While we may not do genetic tests for everyone, we should discuss unclear cases with experts early on. Indicators like age, family history, and extra-renal manifestations guide us. A negative genetic report doesn't mean the disease isn't genetic; it requires interdisciplinary discussion to interpret."

Interpreting genetic reports can be challenging, especially copy number variations (CNVs). Prof. Sayer, could you explain?

JS: "CNV involves duplications or deletions in genetic regions, affecting one or several genes. Detecting CNVs used to rely on microarray, but now we use whole exome and genome sequencing. However, these new methods can sometimes miss clinically significant CNVs. For example, complete gene deletions might be overlooked because the gene isn't present to detect any variants. Understanding these nuances is vital."

How prevalent is the genetic contribution to renal disease in adults?

JS: "About a third of individuals with renal disease have a genetic contribution. We are still learning about the implications of carrying genetic variants and their penetrance. Environmental factors also modulate the disease course."

What is the role of large collaborations like the 100,000 Genomes Project?

JS: "Large sequencing projects, like the UK's 100,000 Genomes Project and the All of Us project in the USA, are invaluable. They provide a wealth of data, helping us understand genetic variations across different populations. This knowledge helps reclassify variants and better understand their significance."

RM: "These collaborations are crucial. They allow for large-scale clinical studies and international collaboration. Societies like ERA link people together, facilitating these studies and advancing our understanding."

What advice would you give to GPs seeing patients with potential genetic issues?

JS: "GPs should have access to genetic tests to target referrals effectively. They need to overcome the fear of genetic testing and interpret the results. The next generation of doctors needs to handle large data sets and understand genetic information."

RM: "For now, GPs should know the experts in their country and reach out for discussions. Education is key to overcoming prejudice towards genetic testing. In Germany, for instance, there is a misconception about the cost and impact on practice budgets, which isn't an issue. We need to educate everyone involved to ensure patients get the necessary tests."

Do you think whole genome sequencing at birth could become standard practice?

JS: "This is being piloted in Birmingham, UK. The idea is to sequence a baby's genome at birth and apply different panels at various life stages. It's exciting but raises ethical and resource-related questions."

RM: "This requires a parallel discussion at the societal level. We need to prepare everyone for the ethical implications. This process is unstoppable and offers many advantages, but we must address these questions proactively."

Thank you both for this insightful discussion. Your expertise and dedication to advancing nephrology are truly inspiring.

LinkedIn profile Prof. John Sayer

LinkedIn profile Prof. Roman-Ulrich Müller

 



Posted on 5 June 202425 June 2024