View all news

Finding more pieces for the Nephrotic Syndrome puzzle

Dr Anna Mason

21 October 2020

Research at the University of Bristol is leading the way towards new understanding of a difficult-to-treat kidney disorder in children. Dr Anna Mason is studying the genetic basis of paediatric Steroid Resistant Nephrotic Syndrome.

Nephrotic syndrome

Nephrotic syndrome is a group of symptoms caused by kidney damage. It’s characterised by large amounts of protein in the urine. In children with the disease, the syndrome usually responds well to steroid treatment. Some children, however, don’t respond to steroids, and require much stronger immunosuppressant treatment instead; this is known as Steroid Resistant Nephrotic Syndrome (SRNS). The prognosis for these patients is not clear. At present, it’s difficult for doctors to predict whether they will respond properly to these stronger drugs (some don’t), whether they may develop kidney failure in the future and require a kidney transplant, or whether this kidney might also develop the same disease.

Dr Anna Mason, a medic working in Paediatrics at Southmead Hospital, Bristol, used the Clinical Primer Scheme from the Elizabeth Blackwell Institute to research the underlying disease mechanisms.

New mutations

Dr Mason said, “My colleagues in Bristol Renal have recently identified three new potential mutations in novel genes (the vitamin D receptor and SMAD7 genes), which are likely to play a key role in the SRNS disease process and shed light on basic biological processes. The purpose of my project was to establish the functional consequences of these three mutations in renal podocyte cells, which are the main target of injury in nephrotic syndrome. I also undertook a study to determine the response to immunosuppression and rate of post-transplantation disease recurrence in paediatric patients with SRNS.”

Working under the auspices of Professor Moin Saleem at Bristol Renal, Dr Mason and the team studied data from 274 children with nephrotic syndrome who had been treated with immunosuppressants.

“If the patient had a genetic basis to their disease, fewer than 4 percent of them responded well to immunosuppressant treatment,” said Dr Mason. “However, in these cases, a kidney transplant was curative.”

“It was different for patients who had no genetic basis for their disease though. In these cases, if they responded to their first immunosuppressant treatment, they were very unlikely to develop kidney failure (less than 3%) and had a good long-term outcome. But if they did not respond, nearly half of them developed kidney failure and needed a transplant - but in over 70% of these patients, the disease recurred in the new kidney. Kidney biopsy at diagnosis did not predict their response to medication or their long-term outcome.”

Accurate information

These results will help doctors to plan the most appropriate treatment for individual patients and to provide patients with more accurate information about their disease. Genetic testing can determine whether immunosuppressants are likely to be effective.

“The response of patients to a particular immunosuppressant, called Rituximab, has also given new clues to the underlying cause of nephrotic syndrome in the body’s immune system and is worth further investigation’” said Dr Mason.

Clinical Primer

The Clinical Primer Scheme is designed to help medical, veterinary and dental trainees to experience a world-class research environment for the first time.

“At present I am undertaking a ST1 training post in Histopathology - the Clinical Primer Scheme was key to my successful application. The laboratory-based skills, research experience, and understanding of the link between pathology and clinical disease that I gained made me an ideal candidate - and will continue to be very valuable throughout my future career. The opportunities I have had to present my work, both as posters and orally, and to develop manuscripts for publication have strengthened my CV for a successful PhD Fellowship application in the future. They have also developed my writing, presenting and critical appraisal skills which will be extremely helpful in both my academic and clinical career. In August 2021 I will begin the Wales Clinical Academic Track (WCAT) fellowship programme.

Further information

PubMed paper: Response to First Course of Intensified Immunosuppression in Genetically Stratified Steroid Resistant Nephrotic Syndrome

Edit this page