Scientists may have found a way to heal damaged kidneys

What if kidney damage did not have to be permanent? A drug originally developed to help heart tissue repair after a heart attack could soon offer new hope to millions with kidney disease.Researchers at the University of California, Los Angeles (UCLA) have found that a heart drug may have a second act by helping kidney tissue repair and regenerate. During an animal study, the researchers found that blocking a specific protein dramatically improves kidney repair and reduces scarring in mice, and the treatment is already advancing towards human trials. The findings are published in Cell Stem Cell.

A drug with a dual purpose

The drug, called AD-NP1, previously developed by UCLA researchers, was recently approved by the FDA for a Phase 1 clinical trial in humans.

This drug works in heart tissue by blocking a protein that disrupts healing and prevents internal organs from fully recovering. The researchers have now found that blocking this protein in kidney tissue speeds repair after kidney injury in mice.The new findings build upon many years of research in the laboratory of UCLA cardiovascular scientist Arjun Deb. His team found that an injured kidney produces a protein called ENPP1.

This protein initiates a metabolic chain of events that disrupts energy production and the function of multiple cells in the injured region, slowing down tissue repair. The researchers have now found that blocking this protein improves kidney repair and also reduces scar tissue formation.

Both help to improve kidney function. The researchers had earlier discovered that blocking ENPP1 in heart tissue improved healing.The researchers looked at kidney biopsies from people with chronic kidney disease. In these patients, the protein ENPP1 was expressed at higher levels than in healthy tissue. To understand the impact, the researchers conducted studies on mice. They found that the protein was linked to significant increases in serum creatinine, BUN, and cystatin C, all signs of renal dysfunction. Four weeks later, mice that could not produce ENPP1 showed much better recovery.

This suggested that their kidneys were healing.“These animals had a far better outcome. Their kidneys were not as damaged, and the kidney cells were proliferating more. We found that the same mechanisms we observed in the heart were also applicable in the kidney. After injury, healthy cells around the damaged area were trying to proliferate, but the damaged area was sending metabolic signals that prevented the kidney from regenerating and repairing effectively,” said Deb, a UCLA professor of medicine and of molecular, cell and developmental biology, and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.In September, the drug was approved for Phase 1 clinical trials in humans for the heart. In this trial, the safety, dosage and metabolism of the new drug will be evaluated. This is the first step towards trials assessing its efficacy. The researchers are planning to apply for trials in the kidneys as well.