Fixing leaky kidneys
Diabetes can cause the kidney’s filter to become damaged so it leaks out protein, and this can lead to kidney failure. But interesting new research that we funded shows that it might be possible to plug those leaks before they cause too much damage.
For people with diabetes, the chances of developing kidney disease are relatively high. In fact, people with diabetes are five times more likely to need either kidney dialysis or a kidney transplant. And as diabetes progresses, the kidneys can become more damaged over time, until they no longer work properly. We call this diabetic kidney disease, or diabetic nephropathy, and it’s the main cause of kidney failure.
When your kidneys aren’t working properly, your body can’t keep hold of the things it needs, such as protein, and it leaks into the urine.
We can spot kidney damage quite early on by looking for a specific protein, called albumin. When albumin appears in the urine (which we call albuminuria), it can lead to additional complications like heart and circulatory disease and other related issues.
Sadly, there are very few treatment options for diabetic kidney disease. But now, interesting research in mice suggests there could be a way to stop albumin leaking into the urine, potentially offering a new treatment for those with diabetic kidney disease.
How do kidneys “leak”?
Your kidneys work like an incredibly smart filter – they sift the blood into what should stay and what should go. One of the key parts of your kidneys that do this is a small structure called the glomerulus – which acts like a sieve at the start of the filtering process.
When your blood flows into the kidneys, and through the glomerulus to be filtered, it passes over a group of very flat cells called glomerular endothelial cells. One of the important jobs of these cells is to stop protein leaking out from the blood and they do this with the help of a specialised surface coating, made of sugars, to form a barrier that we call the glycocalyx.
Research just out from the University of Bristol, by Dr Raina Ramnath, has uncovered enzymes – specialised proteins in the body – that break down that glycocalyx barrier and let albumin pass between the flat glomerulus cells, and out into the urine.
Dr Ramnath has discovered a group of enzymes known as matrix metalloproteinases (MMPs) that are responsible for damaging the glycocalyx. Her work has also highlighted that there are more MMPs in the diabetic mice disease than in ‘healthy’ mice, which might explain why the diabetic kidneys were leaking.
Protecting the barrier
With MMPs (specifically MMP2 and MMP9) explaining why albumin leaks across the glycocalyx, Dr Ramnath and her team set to work to figure out how to plug it. The solution was to use an inhibitor - a molecule that stops (or ‘inhibits’) another molecule working. In this case, the inhibitor stopped MMP2 and MMP9 from damaging the glycocalyx sugar barrier in the glomerulus.
After six weeks receiving the MMP2 and MMP9 inhibitors, the glycocalyx barrier in the mice was thicker and present across all of the flat glomerulus endothelial cells. The MMP inhibitors had plugged the albumin leak to stop it passing out into the urine.
Treatment for diabetic kidney disease?
While this is fascinating, we must remember this is still early-stage lab work.
Dr Ramnath’s work has highlighted that inhibiting this group of MMPs in mice can help to reduce albumin leaking out of the kidneys into the urine. There’s still a great deal of research to be done but it is incredibly exciting to see MMP a very likely target of treatment in the future.
Dr Ramnath’s results were published in the journal Kidney International and were funded by Kidney Research UK.
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