Scientists tap new method to reduce progression of kidney disease in diabetics

A groundbreaking study led by researchers at England’s University of Bristol has revealed a promising new approach to slow down the progression of diabetic kidney disease, a condition affecting 40% of individuals with diabetes. 

Published in JCI Insight, the study offers hope for the millions of people in the world with diabetes. Diabetics are at a significantly higher risk of requiring dialysis or kidney transplants. 

The research focuses on the use of spironolactone, a blood pressure medicine that has shown efficacy in reducing protein leakage into the urine. By understanding how spironolactone preserves the glycocalyx layer on blood vessels within the kidneys, scientists aim to develop alternative therapeutics that replicate the protective effects without the adverse side effects associated with the drug.

Spironolactone can have adverse side effects, including high blood potassium levels (hyperkalaemia), which has made clinicians hesitant to use it in the past. In an effort to understand how spironolactone prevents kidney damage, researchers from Bristol Medical School collaborated with international colleagues, the University of Bristol said in a release. The researchers discovered that the drug has a protective effect by preserving the gel-like glycocalyx layer on the surface of blood vessels within the kidney. 

The team aims to develop novel alternative therapeutics that can slow down the degradation of the glycocalyx layer directly, potentially recreating the same protective effect without the adverse side effects associated with spironolactone. To conduct their study, the researchers used patient kidney biopsy specimens to develop a new method for measuring changes in the depth of the glycocalyx layer, confirming that diabetes damages the endothelial glycocalyx layer and that spironolactone prevents this damage.

The results of the study indicated that spironolactone reduces the activity of a group of enzymes known as matrix metalloproteases, which helps preserve the glycocalyx layer, thereby preventing the progression of the disease. 

"This study is really exciting for us because it confirms that blocking mineralocorticoid receptors using spironolactone preserves kidney function by acting on the glycocalyx,” Dr. Matthew Butler, joint senior author of the study and consultant senior lecturer and Medical Research Council clinician scientist at the University of Bristol, said in the university’s release. 

The researchers plan to explore the potential use of drugs that target matrix metalloprotease enzymes to determine if they could benefit patients with kidney disease, while avoiding the troublesome side effects associated with mineralocorticoid receptor blockers, the release said. If these more specific drugs exhibit the same level of protection, patients could experience significant benefits while minimizing the risks of high blood potassium levels.

Dr. Aisling McMahon, executive director of research and policy at Kidney Research UK, commended the innovative approach of the study and its potential to identify new treatments for diabetic kidney disease more efficiently. The study was carried out in collaboration with colleagues from the University of Bari Aldo Moro in Italy, the University of Groningen in the Netherlands, and the University of Texas Southwestern Medical Center in the U.S. Funding for the study was provided by Kidney Research UK, Diabetes UK, the British Heart Foundation, and the Medical Research Council, with support from the University's Wolfson Bioimaging Facility.