My name is James McCaffrey and I am doing a medical PhD. I went straight into medical school after finishing my A-levels, and graduated in 2007. I continued my training as a junior doctor in Manchester before deciding to specialise in paediatrics in 2009. After a few years of being a paediatric doctor, I became interested in children’s kidney disease and began a PhD at the University of Manchester in 2011.
My PhD focuses on a childhood kidney disease called ‘nephrotic syndrome.’ The
medication we have for treating nephrotic syndrome only works for a proportion
of children, and sometimes results in unwanted side effects. No one knows
exactly how this medication works. By trying to understand more about the
important actions the medication has in children with nephrotic syndrome, we
may be able to develop more effective drugs with fewer side effects in the
What is nephrotic syndrome?
One of the main functions of the kidney is to filter the blood, so unwanted substances can be removed from the body. However, it’s also vital that the kidney filter does not let important proteins and minerals leak through. An essential part of the kidney filter is a cell called the podocyte, which keeps blood proteins in the body, while letting substances harmful to the body pass through.
In nephrotic syndrome, the podocytes become damaged and the kidney filter becomes abnormally leaky, so these important blood proteins are lost from the body. These proteins help regulate where water is stored in the body and are needed to fight infection. When they are lost in nephrotic syndrome, children have a high risk of developing serious infections and water moves from the blood into various tissues so patients develop massive body swelling.
How is nephrotic syndrome treated?
Children with nephrotic syndrome receive an 8 week course of a type of steroid called prednisolone (this is very different to the steroids body-builders use!). Some children respond very well to this treatment, the kidney filter returns to normal, and they never have the disease again. Some children respond well initially, but the disease comes back several times over a number of years. Unfortunately, some children do not respond to steroids at all, and more powerful medications are needed. The children who do not respond to steroids during their first treatment course sometimes have long term problems with their kidney.
Why is nephrotic syndrome important?
Approximately 200 new children develop nephrotic syndrome in the UK every year. As late as the 1950’s approximately half of children with nephrotic syndrome died (mostly from infections). Although today we have more effective treatments available, children taking steroids sometimes experience unwanted drug side effects such as weight gain, high blood pressure and acne. Children who do not respond to steroids have a high chance of developing long-term kidney problems, which may ultimately require kidney transplantation.
What do I investigate?
Although steroids have been used in nephrotic syndrome for many decades, no one knows exactly how they work! It’s also unclear why some children respond well to steroids, while others do not. I mainly work on podocytes grown in the laboratory and characterise their response when they are treated with steroids. This involves finding out what new proteins are made when podocytes are treated with steroids, and investigating whether any of these may be important in the response that the kidney filter has in children with nephrotic syndrome when they receive medication.
Steroids do a lot of things: some of them helpful to the kidney barrier, and some of them unhelpful (which is why children experience side effects). If we could understand more about the helpful actions that steroids have in nephrotic syndrome, we may eventually be able to make drugs that are effective for all children with nephrotic syndrome and also have fewer side effects.
More information about nephrotic syndrome from a patient’s perspective can be found here (http://www.nstrust.co.uk/pages/home/aboutns)
Here’s a great website for finding out about all the kidney research happening in Manchester (http://www.gmann.co.uk/website/index.cfm)
An explanation of other projects happening in my PhD supervisor’s laboratory can be found here (http://www.wellcome-matrix.org/research_groups/rachel-lennon.html)
Here are some PhD projects that doctors in the North West are currently working on (http://www.liv.ac.uk/north-west-england-mrc-fellowship-cpt/fellows)