Novel Approach Reduces Diabetic Kidney Disease Progression

Diabetes is the leading cause of kidney disease, however, despite current therapies, there is a large residual risk of diabetic kidney disease onset and progression. Therefore, widespread innovation is urgently needed to improve health outcomes for patients with diabetic kidney disease. Now, University of Bristol researchers and collaborators report a new way to reduce the progression of diabetic kidney disease, which affects 40% of people with diabetes.

The findings are published in JCI Insight in a paper titled, “Mineralocorticoid receptor antagonism in diabetes reduces albuminuria by preserving the glomerular endothelial glycocalyx.”

“The glomerular endothelial glycocalyx (GEnGlx) forms the first part of the glomerular filtration barrier,” wrote the researchers. “Previously we showed that mineralocorticoid receptor (MR) activation caused GEnGlx damage and albuminuria. Here we investigated whether MR antagonism could limit albuminuria in diabetes and studied the site of action.”

Researchers from Bristol Medical School, in collaboration with international colleagues, aimed to understand how spironolactone—a commonly used blood pressure medicine that is an effective treatment by reducing protein leak into the urine—prevents damage to the kidneys.

They found that the drug has a protective effect by helping preserve the gel-like glycocalyx layer on the surface of blood vessels within the kidney.

Their results showed spironolactone reduces the activity of a group of enzymes, called matrix metalloproteases, helping to preserve the gel-like glycocalyx layer on the surface of the blood vessels in the kidney, preventing disease progression.

Matthew Butler, PhD, the study’s joint senior author, consultant senior lecturer, and MRC clinician scientist at the University of Bristol said: “This study is really exciting for us because it confirms that blocking mineralocorticoid receptors using spironolactone preserves kidney function by acting on the glycocalyx.

“Our next steps will be to look at repurposing drugs that target matrix metalloproteases enzymes [MMPs] to see if they could be of benefit in patients with kidney disease and avoid the troublesome side effects associated with mineralocorticoid receptor blockers. If we see that same level of protection using these more specific drugs, then patients will see significant benefits whilst avoiding the risks associated with high blood potassium levels.”

Aisling McMahon, PhD, executive director of research and policy, Kidney Research UK, added: “Improving outcomes for patients is a key priority at Kidney Research UK. This work is an important step that will allow new treatments for diabetic kidney disease to be identified faster. We congratulate Simon and Matt on this innovative approach and look forward to seeing further developments from their team.”

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