Kidney Researcher Studies New Approach to Treat Common Disease

Kidney Researcher Studies New Approach to Treat Common Disease

Kidney researchers at The University of Toledo College of Medicine and Life Sciences have uncovered a promising new approach for treating glomerular diseases, which left unchecked can cause kidney failure.

Inside each kidney are hundreds of thousands of tiny filters called glomeruli that cleanse the blood, screening out waste products and excess water which is removed from the body through urine.

When those filters become damaged, however, they can also allow excess proteins to leak through - a condition known as proteinuria.

"It's kind of a chicken and egg situation," said Dr. Rujun Gong, a professor of medicine and director of kidney research in the UToledo College of Medicine and Life Sciences. "Proteinuria, which can cause persistent foamy urine, is a significant diagnostic sign of kidney disease. But it also exacerbates kidney injury and can lead to other health problems including edema, malnutrition, dyslipidemia and an increased risk of heart disease. It is a vicious cycle."

Hundreds of millions of people worldwide are living with chronic kidney disease. Glomerular disease specifically is the third leading cause of kidney failure.

Controlling proteinuria is one of the key points to clinical management of glomerular disease. Typically, Gong said, that has been done with corticosteroids or other powerful immunosuppressant drugs. But such medications can bring their own set of problems.

"These drugs don't always work, but even when they do, it's like we're using a nuclear bomb. They are not targeted treatments," Gong said. "Steroids have limited effectiveness, high rates of recurrence and significant side effects, including swelling, elevated blood pressure and blood sugar, weight gain and bone loss. They can also make you more susceptible to infection. There is a major need for new therapies that target the underlying mechanisms."

Gong and his team at UToledo have spent years studying glomerular disease, inching ever closer to uncovering new methods of treatment.

In a study recently published in the journal Kidney International, Gong and his collaborators found they could reduce kidney damage and protein leakage by activating a receptor called melanocortin 5 receptor, or MC5R.

Melanocortin receptors are present throughout the body and play a role in skin pigmentation and other biological functions, including regulating inflammation.

Previously, Gong's lab had found activating a separate melanocortin receptor called MC1R could modulate glomerular disease through the immune system.

In the new study, which was funded by a grant from the National Institutes of Health, the team found MC5R activation has a direct impact on protecting specialized cells called podocytes, which maintain the structure of the kidney's filtration barriers.

Glomerular disease can have many causes, including genetic defects, immune disorders, toxins exposure, and infection. While Gong's earlier research held potential for immune mediated glomerular disease, the new finding is more widely applicable.

"If we activate this receptor, we can mitigate the proteinuria and the glomerular injury regardless of the cause because we're directly addressing the downstream effect," he said.

In the latest study, which relied on animal models of glomerular disease, Gong's team used a highly selective compound that could bind to those melanocortin receptors, activating their protective response.

"Our findings suggest a novel, steroid-free therapy might be possible," he said. "Having new, targeted therapies for glomerular disease would be a huge breakthrough."