Treatment of chronic kidney diseases
A group of researchers from the Massachusetts Institute of Technology, Women's Hospital named after Brigham and Harvard Medical School demonstrated a new approach to the treatment of progressive kidney diseases. They claim that their finding can protect kidney cells responsible for blood filtration from destruction.
Diabetes, obesity, hypertension, as well as some hereditary diseases can damage kidney tissue and lead to the formation of focal segmental glomerulosclerosis.
Investigating kidney diseases in model animals, a group of scientists discovered a compound capable of protecting kidney filtering cells and restoring kidney function. The results of the work done can affect the fate of millions of people suffering from kidney diseases.
Over the past 40 years, there have been no progressive changes in the treatment of kidney diseases. Chronic diseases lead to kidney failure, putting the patient before a choice between a kidney transplant or hemodialysis. In both cases, the patient faces a lot of difficulties: from complications during transplantation to death with prolonged stay on hemodialysis. In addition, the treatment of patients with chronic renal failure is expensive for the state.
Using rat models of rare genetic kidney diseases, the researchers searched for genes, proteins and mechanisms that occur when kidney tissue is damaged.
Podocytes are kidney cells responsible for filtration, they must remove toxins from the blood and store the necessary protein molecules in it. The main symptom of podocyte damage and death is proteinuria, that is, the content of protein that the body needed in the excreted urine.
Cultured mouse kidney podocyte, artificially colored electron micrography.
Genetic mutations in focal segmental glomerulosclerosis lead to the activation of the Rac1 protein, which, in turn, activates the TRPC5 protein. At the same time, there is an intense influx of calcium ions into the podocyte, the cell dies.
Observations have shown that TRPC5 is activated by various stressors, and inhibition of TRPC5 can prevent podocyte damage.
Researchers have developed and tested many TRPC5 inhibitors in order to find a compound that can block the process of podocyte death. The AC1903 connection showed the greatest prospects.
In a study on rats with a genetic kidney disease, AC1903 protected podocytes, even if treatment began in the advanced stage of the disease. AC1903 prevented the progression of the process and stopped proteinuria, which indirectly indicates the restoration of kidney function.
Researchers have suggested that AC1903 will be able to cure glomerulosclerosis caused by other causes. In an experiment on rat models with kidney diseases caused by hypertension, AC1903 showed a good result: even with a late start of treatment, renal failure was avoided, and renal function was restored.
The results obtained in the study will help make a long-awaited breakthrough in the treatment of chronic kidney diseases. To do this, a large amount of work needs to be done, including conducting clinical trials of TRPC5 inhibitors in humans. But the prospects are undoubtedly impressive.
Article by Yiming Zhou et al. A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models is published in the journal Sciense.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Broad Institute: New compound stops progressive kidney disease in its tracks.