International Fellowship Programme on Integrative Kidney Physiology and Pathophysiology

Project raises its voice over ‘silent epidemic’ With cases set to rise significantly over the next thirty years, chronic kidney disease has been described as the ‘silent epidemic’. We spoke to Professor Dr Uyen Huynh–Do of the IKPP project about their research into the causes and possible treatments of the disease Recent data shows that approximately 10 per cent of the world population has some degree of chronic kidney disease, which restricts the body’s ability to both remove toxins and retain important molecules, such as aminoacids and proteins, in the blood. The incidence of the disease is predicted to rise further over the coming years, a context in which the work of the IKPP project takes on real importance. “The main goal of the project is to foster a new generation of researchers in the field of integrative kidney physiology and pathophysiology,” says Professor Uyen Huynh-Do, the project’s Training Programme Director. The project covers four key modules – water and salt, acid and minerals, nutrients and drugs

22

and finally oxygen – reflecting the central role of the kidney in maintaining homeostasis, a balanced internal environment within the body. Professor Huynh-Do says it is important to consider the whole organism in this research. “The kidney is central to the whole organism, so if you want to understand kidney physiology you have to have a global view,” she stresses. “It’s not just about the organ itself, or about some cells or molecules. We aim to look at the kidney within the whole organism.”

Functions of the kidney The starting point is an understanding of the kidney’s functions within the body.

One of the main functions of the kidney is

to retain the correct amount of salt and water, which Professor Huynh-Do says is essential to maintaining blood volume and blood pressure. “If you retain salt then you can also retain water, and this makes the blood volume. If you don’t have enough water then your blood volume, and hence blood pressure, decreases; in contrast when you have too much water, the blood volume is too high and this leads to high blood pressure,” she explains. The second important function of the kidney is waste management. “When you eat and work your muscles work and they produce waste. One type of waste is called urea, and the body has to get rid of it, which is the job of the kidney. It does this by filtrating all the blood going through the

EU Research

kidney, which amounts to about 1.2 litres per minute – a fifth of the volume of blood pumped by the heart per minute,” continues Professor Huynh-Do. “On the other hand the kidney also has to retain everything you need – this is not only salt and water, but also various proteins. So all those important things have to be retained and the waste has to be expelled; you really need quite a sophisticated system to do that.”

The kidney’s ability to perform these functions is significantly impaired in people with chronic kidney disease. In particular the glomerular filtration rate, the capacity of the kidney to remove toxins and other molecules from the body, is reduced. “If the capacity is reduced by more than 50 per cent, or if you have any structural changes, then you have chronic kidney disease,” says Professor Huynh-Do. The project is also studying the closely related conditions of diabetes, metabolic syndrome and hypertension, which Professor Huynh-Do says are the most important causes of chronic kidney disease – in fact, hypertension can be both symptom and cause. “We know for example that when a person has advanced kidney disease the vessels into the kidney are sclerotic and rarefied, and the kidneys produce hormones increasing the blood pressure. This is one very important

www.euresearcher.com

reason why people get hypertension,” she explains. “In this case the kidney is really the cause of hypertension. As hypertension goes on it destroys the kidney even more.

You have a vicious circle – kidney disease leads to hypertension, which in turn exacerbates kidney disease.”

The kidney also produces some key hormones such as erythropoietin (EPO), which regulates red blood cell production, and active vitamin D, which is essential for bone maintenance. Lack of either EPO or vitamin D can lead to significant problems which are very difficult to reverse, so the project’s goal is to identify the risk factors in order to prevent kidney diseases. “New-born children have about 1 million nephrons, the working unit of the kidney, in each kidney. The number of nephrons declines throughout the average life-span, and because they are so complex it’s not possible for them to regenerate,” explains Professor Huynh-Do. Among the most important risk factors are diabetes, metabolic syndrome and hypertension, but Professor Huynh-Do says there are also other causes to consider, such as genetics or early foetal events. “Damage to the kidney can begin in the uterus of the mother,” she says. “It has been shown that children who have been born prematurely or are small for their age are more prone to hypertension, cardiovascular disease and

kidney disease later in life. This issue, known as foetal programming, is one of the things we are looking at in our network.”

Treating kidney disease The ultimate focus of this research is to improve treatment. While currently there is no way of restoring the kidney to full functioning, Professor Huynh-Do says it is possible to prevent the progression of chronic kidney disease. “If you prevent proteinuria – loss of proteins through the kidney – or treat hypertension and diabetes, then you can halt kidney diseases. It can be stabilised, this has been shown in multiple studies of tens of thousands of people,” she stresses. The kidneys do not have to work at full capacity to maintain homeostasis; for example, people can donate a kidney for transplant without compromising their ability to remove toxins and produce hormones. “You won’t have 100 per cent function but you will still have 50-60 per cent, and this is absolutely enough to get rid of the body’s waste and to produce enough EPO and the other things you need,” says Professor Huynh-Do. “Normally both kidneys should work at the same time. But you don’t know, unless you go to the Doctor and they look at your blood samples and maybe make a

23

At a glance Full Project Title International Fellowship Programme on Integrative Kidney Physiology and Pathophysiology Project Funding The project budget is €3.158.532 of which €1.263.412,80 (40%) is funded by the European Commission’s 7th Framework Programme under the Marie Curie COFUND scheme.

Project Partners • University of Bern (coordinator) • University of Basel • University of Geneva • University of Lausanne • University of Zurich www.ikpp.unibe.ch/content/res/ri/ Contact Details IKPP training programme director, Professor Uyen Huynh-Do Department of Nephrology and Hypertension, Bern University Hospital, CH-3010 Bern T: +41 31 632 3141 E: Uyen.Huynh-Do@insel.ch W: www.ikpp.unibe.ch/content Professor Uyen Huynh-Do

Training programme director

Uyen Huynh-Do was trained as an MD at the University of Zurich, where she specialised in internal medicine and nephrology. In 1996 she joined the Center for Vascular Biology at Vanderbilt University (USA) as a postdoctoral research fellow. In 2004 she was appointed assistant professor, and in 2008 associate professor at the University of Bern. In 2009 she received a Master in Medical Education (MME) from the University of Bern and the University of Illinois (Chicago).

sonography of your kidney, how your kidneys are functioning. Some people never even know whether they have two functional kidneys.”

This points to the difficult of diagnosing kidney disease before it reaches a chronic state. Most kidney disease patients go to their Doctor because they feel tired or have hypertension, by which time Professor Huynh-Do says the disease has typically progressed to quite an advanced stage. “The Doctor takes a blood sample and finds the kidney is not working. But at that time the kidney may be working at only 15 per cent of its normal function, which of course is too late,” she says.

People with a family history of kidney disease can be diagnosed quite early, but

Since cases of hypertension, diabetes and metabolic syndrome are likely to rise further over the next 30 years then you could also expect that the incidence and prevalence of kidney disease will rise over that period as well these cases are relatively rare and the predicted rise in cases of chronic kidney disease is more due to increases in hypertension, diabetes and metabolic syndrome. “About 30 per cent of the patients on dialysis in the industrialised world have diabetic kidney disease,” says Professor Huynh-Do. “Since cases of hypertension, diabetes and metabolic syndrome are likely to rise further over the next 30 years then you could also expect that the incidence and prevalence of kidney disease will rise over that period as well.”

The future This trend has led the World Health Organisation to describe chronic kidney disease as the ‘silent epidemic’, further

24

underlining the urgency of the situation.

With researchers looking to understand the disease in greater depth, Professor Huynh-Do believes effective collaboration between basic scientists and clinicians is crucial to improving treatment. “We have multiple studies on treatment of hypertension and we also have other studies dealing with bone disease in patients with kidney diseases, an important, costly public health issue,”

she outlines. With funding in place for the next few years the project is pursuing research across a range of areas, reflecting the complexity of the kidney and its importance within the body. “We are beginning some projects in clinical nephrology which we think are quite important. For example, we are setting up a Swiss kidney stone cohort. This is really something we can treat quite effectively,” says Professor Huynh-Do. “We also have another study going on into patients with liver cirrhosis and kidney diseases. Liver dysfunction leads to kidney dysfunction, so we can also try to treat that. Currently we have several clinical research projects going on as well alongside our fundamental work.”

EU Research