A look at some of the fantastic paediatric research taking place this year across the UK.

You might think that when it comes to kids and kidney disease that it’s just a matter of dealing with a smaller patient. But it’s not that simple. Yes, kids are smaller, but they also have plenty of physiological differences compared with adults, like heart rate and how they respond to medicines. That’s why understanding how kidney diseases specially affect kids is a matter that deserves our attention.

Here are some of the exciting new paediatric research grants we funded earlier this year throughout the UK, thanks to our merger with Kids Kidney Research.

Genes and faulty bladders

Over 900,000 children in the UK have bladder problems that cause bed-wetting, incontinence, constipation, infections and even severe kidney damage. These bladder and bowel issues can really hurt children’s self-esteem, education and relationships.

Inherited bladder problems

One of the grants we’ve funded in this area went to Professor William Newman at the University of Manchester. William has spent the last decade trying to find the genes responsible for inherited forms of severe bladder problems, which can often result in kidney failure.

These inherited conditions usually affect young children who go on to need expert care. William and his team have already discovered changes in several genes that they think play a significant role. But there’s still more to know.

In this new research project, William is using the entire genetic information from 40 people affected with bladder disease, along with the huge amount of information already in the 100,000 Genomes Project. This will allow the scientists to study a cell’s complete genetic material, rather than investigating little bits at a time.

If successful, this project may help doctors better explain the genetic reason for their children's bladder problems to families, check if they need regular check-ups, and find new ways to develop treatments. It would also mean doctors could screen family members for the same problem genes. This work could even offer insights into children who suffer from more common bladder and urinary problems beyond these rare inherited types, like reflux.

William and his team are working with affected families so they can help guide how they approach these studies and share information about results through charities like ERIC, the Children's Bowel and Bladder Charity.

Faulty bladder nerves

Another new research project is from Dr Neil Roberts, also at the University of Manchester. Like William, Neil is looking at inherited forms of bladder disease that eventually lead to kidney failure. He believes they happen because of faulty nerves going to and from the bladder.

Neil’s research will use sophisticated techniques to figure out why these bladder nerves don’t seem to be working properly. Using genetically engineered mice, Neil plans to see how a few specific genetic changes might affect how well the bladder empties and refills. From there, they’ll take a closer look at the nerves themselves, looking at how they connect to the muscles in the bladder and how these nerves might chance with age.

William and Neil’s research at Manchester mean we may better understand genetic forms of bladder disease and find new ways to manage and treat them.

Predicting kidney disease in IgA vasculitis

In people with IgA vasculitis, an immune system protein called IgA finds its way throughout the body and collects in small blood vessels, which become inflamed and leak blood. IgA causes rashes, sore joints, tummy pain or, in some cases, kidney damage. While most children make a full recovery, a few (one to two in every hundred) develop severe kidney disease. Right now, we have no way of knowing who will, and who won’t, get better.

Dr Louise Oni from the University of Liverpool wants to develop a way to predict this kidney damage. Louise thinks that looking at several types of IgA is the key and their early work has already picked out 25 variations. Of these 25, two were remarkably different in children with IgA vasculitis compared to those in healthy children. The researchers now need to look at a bigger group of people to make sure these differences are real.

Louise will start with 40 patients, looking at healthy individuals and comparing their IgA proteins with those who already have IgA vasculitis. The results will give a much clearer picture about which IgA versions are most likely to cause kidney problems.

If successful, this project could offer doctors the ability to better predict which children with IgA vasculitis will develop kidney problems. As a result, parents and carers would have a clearer understanding of the path ahead of them. Louise’s vision is: “No child with IgA vasculitis will get chronic kidney disease.” This project will take us a step closer to achieving this.

Designing bespoke dialysis equipment for children

Around 200 children in the UK are on dialysis and half of them have haemodialysis, or HD. Dialysis is tough – around three times a week, blood is pumped out of the body and into an ‘artificial kidney’ machine through a plastic tube called a central venous line, or CVL. The lines used in children are miniature versions of the ones used in adults.

But CVLs can bring a lot of problems. In infants and young children, blood can flow very slowly through the lines, or the tip can get stuck against a blood vessel wall and damage or block it. If this happens, the dialysis machine can’t filter blood well enough during dialysis and blood clots can develop. In fact, doctors remove around 45% of all CVLs from children, which requires them to have an operation under general anaesthetic. Removing and replacing CVLs repeatedly could damage the blood vessels permanently and prevent their dialysis ‘life-line’ working – and children could die.

Dr Rukshana Shroff and her team of biomedical engineers and doctors at University College London (UCL) and Great Ormond Street Hospital are working together to find links between these CVL complications and their design.

They will then create 3D computer models of children’s hearts and blood vessels and 3D printed models of the children’s hearts and blood vessels in different sizes. They’ll connect the 3D printed models using artificial blood to simulate real life as closely as possible and will test the lines and safely test their new design ideas.

This exciting research could lead to newly designed CVLs made just for children on dialysis, which will make it much safer.

The protein problem behind nephrotic syndrome

At the University of Bristol, Dr Gavin Welsh is carrying out research that might identify tell-tale proteins that could improve how well we understand nephrotic syndrome, and how soon we spot it.

Nephrotic syndrome is a devastating kidney disease that particularly affects children. When you have nephrotic syndrome, your kidneys leak lots of protein into your wee. That might not sound like much, but it can cause severe swelling (especially around the eyes and ankles), high blood pressure, fatigue, weight gain and your kidneys fail to work how they should.

Steroids are the first line of defence, but unfortunately for around 20% of people they have no effect. These people have steroid resistant nephrotic syndrome (SRNS) - they suffer long-term illness, and their kidneys can fail. Currently, there are no good biomarkers” – molecule such as proteins that flag if someone has a disease - to predict the disease or how well a prescribed treatment is, or isn’t, working.

Gavin’s team at the Bristol Renal Unit will use data already in the NURTuRE (National Unified Renal Translational Research Enterprise) biobank. This biobank holds anonymous information from nephrotic syndrome patients and is brimming with detail like follow-up examinations, demographic data (age, weight, gender, etc) as well as more in-depth information like genetics and blood test results. The NURTuRE biobank has had generous funding from both industry and Kidney Research UK.

In this research project, Gavin aims to use blood from different people with nephrotic syndrome to identify new and specific biomarkers for this disease. He will try to spot how levels of various proteins change throughout the body. Gavin believes there should be higher or lower amounts of certain proteins. Measuring these can tell doctors a lot more about the condition – ideally before symptoms become severe.

If Gavin and his team can identify the “signature” of all protein changes from people with nephrotic syndrome and compare this with healthy individuals, they might spot new biomarkers and better understand the disease. They also plan to combine these results with NURTuRE biobank data so that there’s even more information on patients available to help guide treatment and prognosis.

Cell catcher: kidney cells from wee

What if doctors could simply get kidney cells from urine? No needles needed. Professor David Long from the Institute of Child Health at University College London may have a “cell catcher” that could do just that.

Bardet-Biedl syndrome (BBS) is a rare genetic disease with lots of symptoms, including blindness, kidneys not working properly and extra fingers or toes. BBS affects around 1 in 125,000 people and around 500 of them attend regular specialised clinics in Birmingham and London, making it one of the best-studied groups of BBS patients in the world. But despite all this information, there's still no treatment for the condition.

To get a handle on this disease, scientists need cell samples. Right now, scientists mainly study animal models of the disease and genetically modified cells, but cells straight from BBS patients are likely to be the most useful. To get these cells, a biopsy is one option, but this isn’t always the most comfortable procedure – especially for children.

But there is another way to get cells. Every day, dozens of cells from your kidney come out in urine. This is completely normal but, of course, those cells usually end up in the toilet.

To get these kidney cells, patients would normally need to travel to the hospital to give a sample. The lab needs to process it right away but even then, getting these cells out of a urine sample safely on to a petri dish is a challenge! But David’s team is looking at a way that children with BBS can produce a wee sample at home, using a special “cell catcher” device, and send their samples to the lab.

David’s research will start by collecting samples from volunteers before extracting cells and preserving them.

Getting cell samples from people with BBS is a brilliant idea: it’s simple, reliable, uses a freely available biomaterial (urine!), and doesn’t require any form of biopsy. This work will benefit kidney scientists and doctors around the world, as it could eventually help them study, diagnose and treat this disease much faster.