Researchers from Bristol Medical School, in collaboration with international colleagues, aimed to understand how spironolactone prevents damage to the kidneys.
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.
Diabetic Kidney Disease: New Findings
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.
Dr. Matthew Butler, the study’s joint senior author, Consultant Senior Lecturer and MRC Clinician Scientist at the University of Bristol and Honorary Nephrology Consultant at North Bristol NHS Trust (NBT), 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.”
Dr. Aisling McMahon, 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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