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Blocking mineralocorticoid receptors preserves renal function in diabetes

Blocking mineralocorticoid receptors preserves renal function in diabetes

 


Glomeruli (kidney filters) in diabetic patients.Diabetics have no visible glycocalyx in their blood vessels indicating diabetic kidney disease
Glomeruli (kidney filters) in diabetic patients.Diabetics have no visible glycocalyx within their blood vessels [University of Bristol].

A study led by the University of Bristol in the UK showed that blocking the activation of mineralocorticoid receptors could help treat diabetic kidney disease, a condition that affects about 40% of people with diabetes. suggesting.

Kidney disease disproportionately affects people with diabetes, who are four times more likely than nondiabetics to require dialysis or a kidney transplant.

“Blocking the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker reduces the risk of albuminuria and end-stage renal disease. However, due to aldosterone escape, [these medications] We may not be able to reduce aldosterone-mediated stimulation of mineralocorticoid receptors,” Matthew Butler, consultant senior lecturer and MRC clinical scientist at the University of Bristol, and colleagues write in the journal. JCI Insight.

A common blood pressure drug called spironolactone, which blocks the activation of mineralocorticoid receptors, has recently been shown to be effective in treating this aspect of diabetic kidney disease by reducing the amount of protein entering the urine. However, it may have adverse effects such as high blood potassium levels.

Butler and colleagues in the UK, Italy, the Netherlands, and the US conducted the current study to more fully evaluate the mechanism of action of spironolactone in diabetic kidney disease. When the researchers examined kidney biopsy samples from patients with diabetic kidney disease treated with spironolactone, they found that spironolactone protects the kidneys by helping maintain the gel-like glycocalyx layer on the surface of the blood vessels in the organ. discovered to do The first part of the glomerular filtration barrier.

The researchers also studied rats with diabetic kidney disease and found increased albuminuria, glomerular albumin permeability, and glomerular matrix metalloproteinase levels with damage or loss of the glycocalyx layer.Butler and team found that blocking activation of mineralocorticoid receptors in rats alleviated these symptoms. Similar effects were also seen in human cell lines.

Data from individuals with diabetic kidney disease treated with mineralocorticoid receptor blockers showed reduced levels of matrix metalloproteinases and albuminuria.

“This study is very exciting for us as we have confirmed that blocking mineralocorticoid receptors using spironolactone, by acting on the glycocalyx, preserves kidney function,” said Butler in a press release. Did.

“Our next step will be to investigate repurposed drugs that target matrix metalloprotease enzymes to see if they are beneficial for kidney disease patients and avoid the troublesome side effects associated with mineralocorticoid receptor blockers. If the same level of protection is seen using these more specific drugs, patients will benefit greatly while avoiding the risks associated with high blood potassium levels.”

Sources

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2/ https://www.insideprecisionmedicine.com/topics/patient-care/kidney-diseases/blocking-mineralocorticoid-receptors-preserves-kidney-function-in-diabetes/

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