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Study highlights potential early intervention for diabetic patients at risk of kidney disease

26 March 2024

In new results published in Diabetes, researchers at the University of Bristol, part-funded by Kidney Research UK, have uncovered a mechanism by which a hormone can protect the blood vessels in the kidneys from the damage caused by diabetes. In doing so, the team have identified a potential early treatment strategy to prevent or slow progression of kidney disease in people with diabetes.  

group of males and females from the University of Bristol, sitting around two tables
University of Bristol Diabetes group

The link between diabetes and kidney disease

Diabetes is the leading cause of kidney failure in the UK. One in five people with diabetes will need treatment for kidney disease during their lifetime and almost one in three people who need dialysis or a transplant have diabetes. As well as these treatments being incredibly gruelling for patients, last year, Kidney Research UK produced a health economics report, which estimated that, in 2023, the direct cost to the NHS of dialysis and kidney transplant surgery with follow-up care was £1.05 billion (not including the £225 million spent on transport for patients on in-centre dialysis) and £293 million, respectively.   

Kidney disease associated with diabetes is often referred to as diabetic nephropathy, or diabetic kidney disease (DKD). DKD is also linked to severe health problems like heart disease, nerve damage and vision problems.  

We desperately need more effective treatments that can prevent or slow the progression of kidney disease in people with diabetes, both to improve quality of life for patients, and to reduce the significant healthcare costs associated with managing advanced kidney disease. 

How does diabetes affect the kidney filters?

The glycocalyx is a thin, gel-like layer made up mainly of sugars and proteins that lines the surface of blood vessels that form part of the tiny filters of the kidney (known as ‘glomeruli’). This layer plays a crucial role in kidney function; it has a barrier function, preventing larger molecules like proteins from leaving the body in the urine.  

In diabetes, over time, high blood sugar levels can lead to damage of the glycocalyx, causing it to break down and become thinner. This damage allows larger protein molecules to leak from the bloodstream into the urine. One of the first signs of kidney disease in patients with diabetes is the presence of a protein called albumin in the urine. 

Kidney damage from diabetes usually happens slowly over many years. Initially, there may be no symptoms, but over time, it can lead to chronic kidney disease and kidney failure in more severe cases.  

Protecting kidney filters

Adiponectin is a type of chemical messenger (‘hormone’) that is produced by fat cells in the body. It plays a protective role in the body: helping the body use sugar more efficiently, reducing inflammation and preventing blood vessel damage. Previous studies have shown that adiponectin levels are lower in people with diabetes and that adiponectin can prevent signs of kidney damage, such as preventing albumin from being lost in the urine in laboratory models of DKD. 

Dr Rebecca Foster, Associate Professor of Microvascular Medicine at Bristol Medical School and senior author of the study, explains: “We knew that adiponectin was protective, but we wanted to understand whether it might be acting by supporting the barrier function of the blood vessels to stop them from becoming leaky.” 

Using several laboratory-based models of DKD, the team were able to show that adiponectin both reduced glycocalyx damage, and restored its depth, which reduced the leakiness of the vessels. Rebecca added: “We were really excited because it's the first time that this fat hormone has been shown to play a role in glycocalyx health. It's a new mechanism of action.” 

Microscopic image of a glomerulus
Image of glomerulus showing small blood vessel with glycocalyx

Stopping DKD in its tracks

As damage to the glycocalyx happens early on in diabetes, before serious kidney problems develop, these new findings suggest that targeting the adiponectin signalling pathway could help to protect the glycocalyx layer in people with diabetes and prevent them from developing DKD. 

Dr Aisling McMahon, executive director research and policy at Kidney Research UK said: “Preventing people with diabetes from developing serious kidney problems is a key priority for Kidney Research UK, both to spare as many people as possible from having to endure the treatments associated with advanced kidney disease, and to reduce the financial impact of kidney disease on the NHS. These findings suggest that targeting the adiponectin pathway might provide a completely new approach to preventing diabetic kidney disease. Further research in this area could lead towards the development of a new preventative treatment for this at-risk group.”  

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