Research into chronic kidney disease
Kidney disease can cause major health problems, as well as raising your risk of heart disease. But there are few ways to treat or even diagnose the condition. Dr Maarten Koeners tells Sarah Brealey how he’s trying to change that, with the help of BHF funding.
Why is chronic kidney disease a problem?
Chronic kidney disease affects millions of people in the UK. If not discovered early it is often too late for any effective treatment and patients will eventually need dialysis or even a kidney transplant.
In the early stages, there are no symptoms, so you're unlikely to know you have the condition. Even so, you’re at higher risk of developing high blood pressure and heart and circulatory disease.
Dr Maarten Koeners in the lab
Chronic kidney disease is a fast growing disease, due to an ageing society and rising rates of diabetes
Dr Maarten Koeners at the University of Bristol is studying this condition. He explains why this is a big problem: “Chronic kidney disease is a fast growing disease, due to an ageing society and rising rates of diabetes - which is a big risk for kidney disease.”
“In the UK chronic kidney disease affects 8.5-9 per cent of adults. One in three people will develop some level of the disease in their lifetimes. It’s a condition that costs the NHS £1.45bn per year, and it kills more people than prostate cancer or breast cancer.
“There are no specific treatments – only treatments for the side effects such as high blood pressure, high blood glucose, and anaemia. And we have only limited diagnostic tests, which don’t work very well in the early stages of the disease.”
Dr Koeners hopes to find out how kidney disease develops and worsens over time, and how we can slow it down or even stop it. He says: “I am hoping to make new breakthroughs, contributing to a cure for chronic kidney disease. So we need to understand how and why someone develops chronic kidney disease which we don’t know at the moment.”
He adds: “My ultimate aim is to go through the whole process identifying, measuring and testing something that would help us develop new treatments, or improve diagnosis, or both. Diagnostic techniques are important too – because better diagnosis means a patient can then be treated in an earlier phase of the disease and/or monitored closely to see which treatment they will need.
“One of the things I am already doing is getting more basic insight into a more individualised approach to medicine. This will help to unravel which patient will benefit from which treatment, as well as looking at possible new drugs.”
A healthy kidney (left); a kidney which is getting less oxygen than it needs (centre); and a damaged kidney (right) - possibly as a result of lack of oxygen.
To do this, he’s studying how kidneys communicate with regulatory systems of the body – including high blood pressure, blood flow, oxygen levels and the activity of nerves.
He’s using telemetry – which means that data is transmitted wirelessly from a monitor to the receiving equipment – to measure kidney function, blood pressure, blood flow, tissue oxygenation, and nerve activity in rats.
He says: “We use state-of-the art devices which communicate via radio signals (using smartphone like technology) which you implant into the abdomen of the rat. We can measure lots of things without the rat being attached to any cables. This is already used for blood pressure recording, but I’m using it to record tissue oxygenation and blood flow, simultaneously, in the kidney – this is a world first.
“The advantages of this are that we can test different drugs in the same animal, which means you can compare drugs more accurately. And it reduces stress for the animal because there aren’t any leads or cables, and you don’t need to handle the animal once the implant is in. Also, I can record 24/7, which is really important, because it makes the data more reliable, and more relevant to the human condition, and will include any effects of the biological circadian clock, i.e. circadian rhythm.”
Dr Koeners is also collaborating internationally on a new technique called hyperpolarised MRI – a minimally invasive test which can measure metabolic changes within the kidney, in 20,000 times more detail than a conventional MRI scan. This hasn’t been used in chronic kidney before.
He says: “It means we are studying what is going on almost at a cellular level. And it is minimally invasive – you inject a sugar-like molecule and within minutes it is gone.”
We are studying what is going on almost at a cellular level. And it is minimally invasive
He is also looking at another advanced scanning technique called BOLD MRI (short for blood oxygen level dependent MRI). This measures relative changes in blood oxygen saturation, so it helps to measure how much oxygen is going into an organ.
He hopes to combine the two techniques, to give an even more complete picture of what’s happening inside tissues of the body in patients with chronic kidney disease.
Blood pressure and oxygen
High blood pressure is also a big focus of his research. Although the heart also plays a role, the kidneys are important in the long-term regulation of blood pressure.
“More than 65 per cent (some research suggests even higher) of patients with chronic kidney disease have high blood pressure,” says Dr Koeners. “High blood pressure will accelerate loss of kidney function and increase risk of heart disease.”
He’s trying to target the way that blood pressure is controlled in order to reduce the problems of chronic kidney disease.
There are also signs that kidney oxygen levels have a role in kidney disease. Dr Koeners says: “The kidneys are unique in that they represent just 1 per cent of body weight but 10 per cent of oxygen usage – so it uses 10 times more oxygen than you expect.”
This is because the kidney is a hard-working organ. The kidneys filter all of the circulating blood in your body many times per day (between 30-60 times) to produce a total filtrate of 180 litres. Of these 180 litres, 99 per cent will be reabsorbed to produce a typical 1.8 litres of urine per day. This process is tightly controlled by transport processes (which use a lot of energy), so the kidney is able to specifically conserve some substances and excrete others.
He says: “All this activity makes it very susceptible to having less oxygen than it needs. This is called hypoxia. My research is looking at how this is related to the development of chronic kidney disease, and whether improving oxygenation of the kidney can help.”
There could be several reasons why the kidneys don’t receive the oxygen they need, including narrowing of the small blood vessels in the kidney, inflammation responses and damage of the filters within the kidney.
Testing new treatments
Dr Koeners is involved in tests of potential new treatments. One is a drug that blocks the effects of aldosterone, a steroid hormone which is involved in regulating blood pressure. This drug will be tested initially on rats with high blood pressure. It’s already being tested for diabetes, and has passed initial safety trials, so could potentially be available within a few years.
Another planned trial will look at the role of mitochondria, the tiny energy generators in the cells, which are the main users of the available oxygen. Dr Koeners says: “We are looking at the idea that in chronic kidney disease, the mitochondria become dysfunctional: they use up more oxygen for the same amount of work. So we are testing how we can prevent mitochondria from wasting oxygen.”
He adds: “I want to get the results I have translated into benefits for patients. These are really exciting times.”
Dr Koeners has received a total of £736,935, including a project grant and an intermediate basic science research fellowship, from the BHF for his research. He says: “BHF funding has been an extremely important opportunity for me, from when I started out as a post-doctoral researcher. I gained confidence along with funding from the BHF to establish my own independent research career.
“BHF funding has really allowed me to grow as an independent researcher and has had a major impact on me as a researcher. This funding has allowed me to climb up the academic ladder and widen my worldwide network.
“The BHF has allowed me to spread my wings. The effect has been really major. I couldn’t be more positive about it.”