Pregnancy and Alport syndrome: a new way to look at the kidney filters
With the support of a Kidney Research UK grant of £170,000, Dr Kenton Arkill and his team at the University of Nottingham are using a new type of imaging technique to investigate how pregnancy impacts kidney health in people with Alport syndrome. The team hope to support future treatment development through their new insights.
During pregnancy the amount of protein in the urine usually doubles, most likely due to increased blood flow and changes to the mother affecting how easily proteins can pass through the kidney’s filters (known as the glomeruli). For patients diagnosed with Alport syndrome the increase is often far higher, with the amount of protein lost in the urine rising to about ten times pre-pregnancy levels. This is of concern as these changes can worsen already poor kidney function leading to kidney failure during pregnancy, with the potential for long term complications.
What is Alport syndrome?
Alport syndrome is a rare inherited (genetic) condition which affects the formation of protein called collagen IV. Collagen IV plays an important structural role in all blood vessel walls, but particularly those of the kidney filter, with hearing loss and eye problems also associated with Alport syndrome.
Alport syndrome is the second most common cause of inherited chronic kidney disease (CKD) after polycystic kidney disease, and individuals with this condition will usually eventually need dialysis or transplant, often at a young age owing to progressive changes to the glomeruli.
Clues from new technology
Kenton and his team think that the increased protein loss seen in individuals with Alport syndrome during pregnancy might be related to changes in filtering molecules – known as glycosaminoglycans – in the kidneys. Glycosaminoglycans are difficult to study using standard laboratory techniques, so Lorna Milne joined the team as a PhD student to work on a new method of detecting the glycosaminoglycans. Lorna has been so successful that the team can use this imaging technique (a type of mass spectrometry known as 3D OrbiSIMS) to study glycosaminoglycans in the glomerulus, and also to look in great detail at the changes in the filtration layers that happen in patients with Alport syndrome.
Lorna added “I was inspired to work in kidney research after my Auntie became a living donor to my Mum. The imaging technique we have developed will allow us to precisely identify how and where glycosaminoglycans are changing within glomeruli during Alport Syndrome and pregnancy. We hope that this information will improve our understanding of the impact of pregnancy and Alport syndrome on the kidneys filtration system, and will support in the development of new approaches to diagnosis, monitoring and ultimately treatment."
This project, which forms part of the Alport Research Hub, begins in October 2024 straight after Lorna completes her PhD. The team is expected to see preliminary results by the new year.
Introducing the Alport Hub
Developed in partnership with the Stoneygate Trust, the Alport Research Hub is accelerating research towards new approaches to early diagnosis and the development of treatments specifically for Alport syndrome.
Better genetic testing and medications called ACE (Angiotensin Converting Enzyme) inhibitors, which slow down the loss of kidney function, have improved the diagnosis and treatment of Alport syndrome in the last decade, but more progress is needed. By enabling the work of a research lab in Manchester, led by Professor Rachel Lennon, and a virtual hub using information from RaDaR (National Registry of Rare Kidney Diseases), led by Professors Danny Gale and Neil Turner, the Alport Research Hub brings together the expertise and resources to drive progress for patients living with Alport syndrome.
The University of Nottingham’s new project grant forms part of the Alport Research Hub programme of work.
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