University of Augusta Study Shows Relationship Between Tubular Autophagy and Kidney Failure in Diabetics

Researchers believe they can explain – in part – the onset of renal failure, particularly in diabetics, by a weakening of kidney cleansing activity. This discovery sheds light on a chain of factors whose modification could lead to new preventive treatments.

Kidney

Kidney

Approximately 30 to 40% of diabetics develop a disease that slowly destroys their kidneys. Although the damage is known, how it happens remains unclear. On August 17, researchers from the University of Augusta published their findings on the phenomenon in The Journal of clinical investigation. They noted that diabetic kidney disease disrupts the kidney cleaning mechanism by decreasing the activity of autophagy, which ultimately “leaves the kidneys more vulnerable,” said Toni Baker, communications director at the university’s medical school.

Read Also: Man Destroys Kidneys With Too Much Vitamin D

“This is the first time we have understood that there is a new mechanism that leads to the dysfunction of autophagy in a chronic kidney disease like diabetes,” says Zheng Dong, a study author and professor of biology and cell anatomy at the University Of Augusta Medical School. I think it also suggests that we have a target path to prevent or slow the progression of renal failure. A great hope for all diabetics.

New Therapies

Researchers noted a sharp decrease in autophagy activity in the kidneys. This decrease in activity causes a proliferation of diseased kidney cells, scars, inflammation, which could then lead to urinary tract infections. To investigate the causes of this dysfunction the researchers used mice which helped them find that the slowing down of autophagy is caused by a drop in the levels of the autophagy activation gene (ULK1), which in turn is caused by the microRNA miR-214, which usually does not participate in this process and yet has increased in the body. This microRNA is in turn controlled by the tumor suppressor (p53), which is known to regulate the cell cycle. Scientists also suspect it may be caused by stress to help eliminate bad cells.

Read Also: Diabetes: Islet Cell Transplantation Under the Skin a Possible Alternative to Insulin Injections

According to the study director, acting on miR-214 would probably make more sense because it clearly seems to inhibit autophagy in diabetes and does not play an obvious role in kidney function. P53, its regulator, is probably not a good target because it limits cell proliferation. Still, it could offer the therapeutic possibility of better regulating autophagy by increasing its action. With this research “We can delay renal failure for 20 or 30 years or even prevent it from occurring in the first place,” says Zheng Dong.

Kidney failure mechanism

This study also provided an opportunity to better understand the mechanism that causes renal failure. The researchers observed that the proliferation of diseased cells in the glomeruli due to an autophagy deficit causes hypertrophy in the tubule, the second filtering chamber of the kidney. The reason? Without the first filtering, the tubular cells face an overload that forces them to multiply their efforts, so they swell up before they get tired. “This process helps the cell fight stress so that it can survive” Zheng Dong analyzes. This malleability also explains the resistance of the kidneys, especially after a blockage of blood circulation or a severe burn.

However, this resilience is affected in people with diabetes, hypertension, and the elderly. Diabetic patients who develop hypertrophy are more likely to develop terminal kidney diseases the scientists noted. Although decreased autophagy may not be the only cause of this hypertrophy, these scientists are convinced that it contributes to the onset of renal failure, especially since cellular stress is a major instigator of reduced autophagy.

Read Also: Type 1 Diabetes: Transplanting Pancreatic Cells Without Anti Rejection Drugs May Soon Be Possible

References

p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease

Conversation

Want to live your best life?

Get the Gilmore Health Weekly newsletter for health tips, wellness updates and more.