Abstract
Our kidneys play a crucial role in body homeostasis, i.e. they provide in a balanced ionic composition, volume, pH and osmolarity of our body fluid, thereby ensuring proper functioning of all our organs. Hence, acute kidney injury (AKI), commonly caused by hampered blood flow, toxins and drugs that typically affect the renal tubular epithelial cells, has far-reaching health consequences with >13.3 million patients each year. When AKI is not lethal, functional recovery of the tubular epithelium usually occurs spontaneously. However, AKI has also been identified as an important risk factor for development of chronic kidney disease (CKD) due to inefficiencies in spontaneous epithelial recovery. To date, there are no treatments that directly heal the injured kidney. Yet, the intriguing biological phenomenon of "nephrectomy-induced renal recovery" might provide a new perspective. This phenomenon comes down to the observation that an acutely injured kidney shows a remarkable degree of recovery and is able to avert progression to CKD when the healthy contralateral kidney is removed shortly after the initial insult. Recently we demonstrated, for the first time, that nephrectomy 1) stimulates proliferation of renal progenitor cells, 2) suppresses detrimental cells, 3) might cause a pro-repair wave of cell death and 4) induces a maximal repair response when performed at the right time after injury. In this project, we aim for profound mechanistic insight in these unexplored processes as they may foster design of new therapeutic strategies. Hereto, we make use of state-of-the-art single cell transcriptomics as well as unique transgenic mouse models to investigate the repair response in relation to its long term outcome.
Researcher(s)
Research team(s)
Project type(s)