Kidney Breakthrough: Scientists Find a Simple Way to Reverse Damage

The kidney is among the hardest-working organs and does not create too much fuss or chaos. However, even while silently doing their job of filtering waste and producing hormones, kidneys sometimes do not get proper care and are damaged. While you may not have too many early visible signs of damage, doctors say most issues are diagnosed when it is too late to treat. However, now there will soon be a way to reverse that damage. In a landmark study published in the journal Cell Metabolism, scientists from the University of Utah Health said they could fully reverse acute kidney injury, or AKI in mice by blocking harmful ceramide molecules. According to the research, ceramides - naturally occurring waxy lipids that are a critical component of the skin's

outer layer- make up about 40 to 50 per cent of it. They act like a "glue" or "mortar" that holds skin cells together, forming a protective barrier that prevents moisture from escaping and keeps environmental stressors out. Ceramides damage the mitochondria of kidney cells, triggering the rapid onset of kidney injury. Acute kidney injury is a dangerous condition often caused by severe stress on the body, such as sepsis or major surgery, and is common in intensive care units. What makes AKI especially alarming is that it can increase the risk of long-term, chronic kidney disease, for which there are very limited treatment options. According to the study, scientists found that when they genetically altered ceramide production, the genetically modified “super mice” did not develop AKI, even under extreme conditions that normally damage the kidneys. The team, led by Dr Scott Summers, also tested a drug candidate that mimics this genetic effect. Scientists observed that mice pre-treated with the drug maintained normal kidney function, stayed active, and showed healthy kidneys. Under closer examination, the team discovered how ceramides wreak havoc – impairing the mitochondria in kidney cells. Damaged mitochondria then become shapeless and lose efficiency, reducing cellular energy production, which causes an injury. But when ceramide levels were reduced, the mitochondria remained intact and worked properly, even under stress.

Future of the drug

While the research promises a possible total reversal of kidney damage in the future, experts believe that it is not necessary that the results of trials conducted in mice will always translate to humans. The drug, developed by US-based Centaurus Therapeutics, is still preclinical, meaning it has not yet been tested in human trials, due to safety concerns. According to Dr Summers, even if lowering ceramides works in humans, the long-term effects, drug metabolism, and side effects need careful evaluation. Also, in the study, the drug was administered to the mice before injury, and so, it is not yet clear whether the same approach would work if administered after kidney damage has already started in a clinical setting. For humans, Dr Summer says his team believes that if the trial succeeds, the mitochondrial health may not only help treat kidney injury but could also be beneficial in other diseases where mitochondrial dysfunction plays a role, like diabetes, heart failure, or fatty liver disease.

What is AKI?

Acute kidney injury (AKI) is a sudden and potentially reversible condition where the kidneys suddenly lose their ability to filter waste from the blood, usually within a few hours or days. This causes waste products to build up in the blood, leading to an imbalance in the blood's chemical makeup. Unlike chronic kidney disease, AKI is a sudden-onset condition, though it can occur in people who are already hospitalized.