Grant: Project Grant

The kidney has a highly specialized filter called the glomerular filtration barrier, which prevents large molecules like proteins from leaking into the urine. This barrier consists of three layers: a basement membrane sandwiched between tiny blood vessel cells (endothelium) and specialized kidney cells called podocytes. When this barrier becomes too porous, proteins leak into the urine, leading to proteinuric kidney disease. Most children with this condition respond well to steroids, but about 10% eventually develop kidney failure. Scientists have identified genetic mutations in podocyte-related genes in about 30% of affected patients, with over 60 genes linked to the disease so far. However, another type of kidney cell, called mesangial cell, also plays a key role in glomerular function, yet very few genetic mutations affecting these cells have been found. Interestingly, we have now discovered mutations in a gene called TNS1 in individuals who have chronic kidney disease and proteinuria. This is the first time a gene primarily expressed in mesangial cells has been linked to proteinuric kidney disease, opening up new avenues for research and potential treatments. This project aims to confirm TNS1's role in CKD and understand how mutations in this gene affect kidney function, using cell, zebrafish and large databases. This research will provide new insights into genetic kidney disease and help doctors use genetic testing more effectively. Ultimately, it could lead to new targeted treatments, bridging the gap between genetic discoveries and real-world patient care.