They say that one rotten apple spoils the bunch, and on a cellular level, that same concept might play an important role in understanding how kidney diseases progress.
Because the kidneys require millions of different cells to work in collaboration with each other, it is thought that injured cells can create a domino effect -- damaging healthy cells which can then contribute to overall kidney function decline.
Understanding how this cellular dysfunction works will help researchers find ways to treat glomerular diseases like diabetic kidney disease, glomerulosclerosis and glomerulonephritis. These diseases don’t just attack the kidneys as a whole, they begin their sinister work at the cellular level, in ways almost impossible to detect.
Ilse Daehn, PhD, an Assistant Professor in the nephrology division at the Icahn School of Medicine at Mount Sinai, is researching what happens to cells within the kidneys when they are injured, and how to prevent the injured cells from causing further damage. With support from a National Kidney Foundation Young Investigator Grant, Daehn aims to understand how different cells respond to kidney disease, and how their dysfunction promotes the progression of chronic kidney disease (CKD).
“We think that preventing dysfunction of kidney cells, particularly glomerular endothelial cells, is key to stopping kidney disease before it reaches the point of no return,” Daehn said. “To do that, we have to understand what is changing within those cells at the transcriptional level.”
Glomerular diseases are the leading causes of kidney failure in the United States, accounting for more than 76% of CKD cases. Being able to identify dysfunctional cells and how they interact with other cells could help in the development of diagnostic tools for glomerular disease. More importantly, it raises the potential to target the cell-damaging mechanisms with pharmaceuticals.
“We are starting to understand the interactions or crosstalk between cells in the glomerulus, and beginning to pinpoint the point of no return were there is enough damage that kidney decline is irreversible,” Daehn said. “Understanding this will allow us to develop therapeutic targets that could stop or prevent further cell injury.”
It is laborious to assess and catalog how cells interact within the kidney. However, Daehn and her team believe they will be able to present and discuss these mechanisms at nephrology conferences in 2016.
The presentation of the findings could also begin the processes of evaluating pharmaceuticals that could prevent cellular damage.
“Our finding may reveal novel drug targets, or that there may also already be drugs on the market that could be repurposed to preserve kidney cells,” Daehn said. “This research will help us decide which mechanism we should be aiming at first.”