Kidneys try to protect themselves during inflammation, study reveals: Study suggests kidneys try to fight of harmful effects of inflammation, which could lead to kidney failure if not combated.
Kidney Protection During Inflammation
In most kidney diseases, the main culprit is inflammation. If the inflammation persists for a long time, it can reduce the kidney’s ability to filter 150-180 liters of blood on a daily basis. If the kidneys stop working then there are only two options: a lifetime of dialysis or a transplant to get a working kidney again.
In a study conducted by researchers at the Medical College of Georgia (MCG) at Georgia Regents University, it was found that kidney cells try to protect themselves from the harmful effects of inflammation by producing an inflammation-suppressing enzyme that is also used by fetuses to survive.
The MCG researchers found that when kidney cells are threatened by inflammation, they produce an enzyme indoleamine 2,3-dioxygenase (IDO). The enzyme helps trigger a series of events, which ultimately end up destroying the damaged protein produced by inflammation. This allows the cells to recover better.
Dr. Tracy L. McGaha, immunologist in the Department of Medicine at the MCG and principle investigator said, “Inflammation can be at root of many kidney diseases- from – from rare conditions, such as Goodpasture syndrome, where the immune system starts producing antibodies against kidney collagen to an infection with hepatitis C to the slow, persistent pounding of hypertension.”
They tested this hypothesis in animal models by first blocking IDO production and then administering a fatal dose of an antibody to collagen of the kidney. This sped up the replacement of the normal kidney collagen structure being replaced with scar tissue that was dysfunctional. This suggested that IDO was the kidney’s way of protecting itself against inflammation.
Even with a reduced amount of antibody, the kidney cell’s destruction was just as rapid in mice with blocked IDO.
The researchers found that the IDO was being produced by podocytes. They are a type of kidney cells with foot-like structures that wrap around the capillaries of the kidney’s filtering units. The kidney can use these podocytes to excrete toxins in the urine and also allow circulation of vital substances, such as sodium.
It has been found that if podocytes are damaged, then the kidney loses its ability to filter. Podocytes have a limited ability of replicating themselves and any damage is more or less permanent.
The podocytes act sort of like the kidney’s gatekeepers and when they fail, substances such as proteins can easily show up in urine. That is why, in a urine analysis, protein levels are measured to check whether the kidneys are working normally or not.
The ability of the kidney to make IDO was not known however. The IDO made by the podocytes eats up an amino acid called tryptophan, which is essential for metabolism. The loss of amino acids triggers a stress signal from the hungry kidney cells, releasing another enzyme GCN2, which causes autophagy.
Autophagy is a cell process, which enables the cell to consume itself, thus helping the cell to replicate. It not only eats up the proteins made by the damaged kidney cells but also slows down production of the proteins. Most of the damage is negated and kidney cells can recover from the inflammation attack.
But if the inflammation has been going on for such a long time, that the autophagy takes too long to do its job, the cell commits suicide. In mice, when autophagy is disturbed, chronic kidney disease is caused.
It was found that the IDO-GCN2 pathway was essential in protecting the kidney cells. The enzyme might become an essential new target for treatment of kidney disease.
It was established in 1998 by MCG research colleagues that fetuses produce IDO to protect themselves from the mother’s immune system. Later studies discovered that tumors use the same enzyme. The research was funded by the National Institute of Health. It was published in the Journal of Immunology.