Medicine, new evidence on acute kidney injury
The study published in Nature Communications by a team from the University of Florence and the Meyer University Hospital revolutionizes the knowledge on the disease, demonstrating how the regenerative capacity of the kidney is limited and function recovery relates to an increase in size of the surviving cells and proliferation of renal stem cells.
Acute kidney injury (AKI) is a common disorder: it affects 13.3 million people in the world, with 1.7 million deaths a year and costs more than breast, lung and bowel cancer together. AKI can be caused by many conditions, such as dehydration, use of certain drugs, exposure to toxic substances, major infections, surgery. Until now, AKI, if not fatal, has been considered as a potentially reversible disease.
A study carried out by Paola Romagnani, head of the Nephrology and Dialysis Unit at the Meyer University Hospital and professor of Nephrology at the Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, and by her group — in particular by Elena Lazzeri and Maria Lucia Angelotti — published in Nature Communications, revolutionizes our knowledge on this important disease.
The team found that the regenerative capacity of the kidney in response to AKI is limited and organ function recovery is largely due to an increase in size of the surviving cells, striving to boost their activity, through endoreplication cycles or endocycles, a mechanism of response never reported . Endocycles are cell cycle variants that permit DNA doubling without cell division. This mechanism, described for the first time in the kidney, leads to a quick recovery of renal function avoiding patient death, but it does not permit the regeneration of damaged tissue.
Therefore, much of the lost tissue is not replaced and even mild AKI episodes leave permanent damage, even in the case of an apparent complete recovery of renal function. This explains why patients who experienced previous AKI episodes show an increased risk of developing chronic kidney disease (CKD) in later years and suggests that every effort should be made to prevent AKI.
The study also showed that regeneration is provided only by a small subset of intrarenal stem cells, that cannot anyway completely repair the damaged tissue. “The good news, however — explains Paola Romagnani — is that the stimulation of renal stem cells with specific drugs is able to enhance their regenerative capacity and avoid the permanent renal damage that can follow to AKI, suggesting that these cells represent an important therapeutic target for this disease “.
The study was funded by a consolidator grant from the European Research Council awarded to Paola Romagnani for the project RENOIR that aims to unravel the functional roles of renal stem cells, identified in 2006 by Romagnani, for disease and kidney regeneration.
