A new way to reduce progression of diabetic kidney disease, affecting 40% of people with diabetes, has been discovered by scientists. The study published in JCI Insight, could help the 4.8 million people in the UK with diabetes who are four times more likely to need either dialysis or a kidney transplant.

Recent clinical trials show a commonly used blood pressure medicine, known as spironolactone, is an effective treatment by reducing protein leak into the urine. However, despite its positive effect, the drug can have adverse side effects, causing problems including high blood potassium levels (hyperkalaemia) in patients, making clinicians reluctant to use it.

Researchers aimed to understand how spironolactone 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. Using novel alternative therapeutics to slow down glycocalyx layer degradation in diabetes directly could now help them recreate the same effect but without adverse side effects.

To conduct this study, the team used patient kidney biopsy specimens to develop a novel method to measure glycocalyx depth changes to confirm that diabetes damages the endothelial glycocalyx layer, and spironolactone prevents this damage.

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.

The study’s joint senior author 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.”

https://insight.jci.org/articles/view/154164

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