Archive for November, 2015

New defences against kidney disease in diabetes

Why do so many diabetes patients develop kidney disease, and how can we improve prevention? EU-funded research has examined insulin-related processes at play in impaired renal function — and it may have found a way to protect key cells that help to filter our blood.
 
The DiaDrug project shed new light on diabetic kidney disease and identified molecules that could be targeted to stop this condition in its tracks. Drugs based on these insights could significantly reduce the risk of progression towards severe forms of the condition that might involve dialysis or even transplants, says project coordinator Sanna Lehtonen of the University of Helsinki.
 
sanna_lehtonen_12031
 
The molecules such drugs would target are also involved in many other metabolic processes, Lehtonen notes. The project’s insights are thus opening up exciting possibilities for treatment of other conditions.
 
Insulin insights
In theory, your kidneys shouldn’t let a molecule the size of albumin cross from your blood into your urine. In practice, small amounts of this protein do get through for many people.
This phenomenon is known as albuminuria. Increased levels can be a forerunner of kidney disease, a complication that affects approximately one diabetes patient in three.
“Albuminuria is one of the key features of diabetic nephropathy. The molecular mechanisms associated with its development are not exactly known,” Lehtonen explains.
What is known, she adds, is that patients are at higher risk of developing kidney disease if they are resistant to insulin, i.e. if their cells don’t respond to this glucose-regulating hormone properly. One type of kidney cell — the podocyte, which is central to the organ’s blood-cleansing activity — is known to be sensitive to this hormone, Lehtonen notes.
 
Keeping podocytes in the pink
“Our major aim was to explore the relationship between insulin resistance and albuminuria,” she explains. “More specifically, we wanted to identify the molecules in the podocytes that make them insulin resistant or affect their glucose metabolism.”
Pinpointing these molecules is difficult enough, but it was merely a first step for DiaDrug. “Once you identify these proteins and you see that their activity is increased in diabetes, you know that by inhibiting them, you can sensitise the cells to insulin,” Lehtonen adds.Of course, the inhibitors – small molecules that disrupt their function – then still need to be found.
DiaDrug’s search was successful. “We have found a protein that is more active in diabetes in tissues responding to insulin, as well as several small molecules that can bind to this protein and inhibit its activity,” Lehtonen reports.
It’s a promising discovery, which could eventually help to reduce insulin resistance and stop the progression of kidney disease for many at-risk patients. However, says Lehtonen, there is still a long way to go to develop these leads into effective, licensed drugs. The entire process could easily take another 15 years, she notes, but the results of the DiaDrug team’s studies on cultured cells, zebrafish and mice are encouraging.
 
Fresh blood
EU financial support for this research came in the form of a Starting Grant awarded by the European Research Council. This type of funding is available to particularly promising researchers at the beginning of their career who are looking to set up their own teams.
“The grant really started my independent career at the University of Helsinki,” Lehtonen notes. It helped to establish her as a research leader, she reports, adding that it may also have played a role in securing the tenure-track position that she obtained during the course of the project.
DiaDrug ended in October 2014, but the work continues. Developing the project’s findings into actual treatments available to patients will be a massive and lengthy task, Lehtonen notes, but the potential is truly exciting.
“Many of the molecules that we work on are present in almost every single cell in your body,” she explains. The ability to control them could thus be of interest for other metabolic conditions, and applications beyond diabetes may be just around the corner.
 

EKHA talks at 2015 US Kidney Organisations Summit

EKHA as a model for multi-stakeholder collaboration

2015 Summit of US Kidney Organizations  
San Diego, November 4, 2015

 
EKHA was invited by the American Society of Nephrology (ASN) to attend the 2015 Summit of US Kidney Organizations, which took place during the annual ASN Kidney Week, to present EKHA’s work at European level, EKHA’s model for advocacy cooperation and to share advice on how to enhance concerted action in the USA. Prof Raymond Vanholder, EKHA Chairman, Prof Andrzej Wiecek, President of the European Dialysis and Transplant Association – European Renal Association (ERA-EDTA) and Ms Monica Fontana, Executive Manager of ERA-EDTA attended on behalf of EKHA.
 
Prof Vanholder presented EKHA, particularly emphasizing the current composition of the alliance. He outlined the importance of the composition, which allows an open and facilitated discussion, but does not reduce each member’s role to report back to its Association. The board, which is made of the four full EKHA members, actually represents several thousands of European individuals, and counts on the involvement of Associate Members, which are national kidney-related societies.
 
Prof Vanholder then laid out different aspects of EKHA’s recently-launched recommendations on sustainable kidney care, as well as the actions that being undertaken or planned at EU level as well as with the national Governments:
 
-Prevention and early detection: control and appropriate treatment of diabetes and hypertension, education (not only of nephrologists, but also of the general public, nurses and primary care physicians), life-style measures (combat obesity, smoking, lack of exercise, high salt and phosphate diet), early detection.
 
-Patient choice of treatment: focus on home treatment for dialysis, conservative care in case of comorbidities.Transplantation: activation of both living and deceased donation programs, opting out for deceased donation.
 
-More rational reimbursement strategies: reimbursement favoring patient choice of care and in proportion to real costs.
 
-He also summarized the set of strategies that are being considered for implementing the recommendations. These include dissemination through personal networks, endorsement by sister societies such as ASN or ISN, involvement of otherstakeholders such as the WHO, andsupport from MEPs (especially EKHA-related working groups) and national societies.
 
Prof Vanholder also highlighted the importance and the purpose of the partnership with the European Chronic Disease Alliance (ECDA). As EKHA, together with several other chronic disease societies is a member of ECDA, all disorders are linked in a partnership and a common approach can be adopted. This facilitates exchanges with EU policy-makers, who indeed favor discussion with organizations that are grouped into one. EKHA’s actions thus rely on four different levels: national societies, the European professional societies such as ERA-EDTA, EKHA itself and the ECDA.
 
To conclude, Prof Vanholder highlighted the benefits of a reduced group, which prevents form having confused discussion and enables to identify a common interest.
 
EKHA US counterparts welcome EKHA’s focus on research and prevention
The open discussion following EKHA’s presentation revealed that EKHA’s American counterparts experience similar problems in their interaction with political representatives. However, differences were also highlighted on specific aspects. The overall debate demonstrated goodwill from US organizations to adopt a similar structural approach as EKHA’s, with emphasis on prevention and research.On this positive note, Ms Fontana encouraged the organisations to stepwise action into building cooperation, as this process could take a while.
 
The Summit of US Kidney Organizations is an annual meeting during ASN’s Kidney Week, gathering representatives of the major societies and foundations representing kidney patients and health professionals of the USA. The 2015 meeting had the aim of fomenting coordination and joint action between US groups devoted to kidney patients and health professionals, in their relations with the policy-makers in Washington DC. 
 
You can download the document here