A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models

Progressive kidney diseases are often associated with scarring of the kidney’s filtration unit, a condition called focal segmental glomerulosclerosis (FSGS). This scarring is due to loss of podocytes, cells critical for glomerular filtration, and leads to proteinuria and kidney failure. Inherited forms of FSGS are caused by Rac1-activating mutations, and Rac1 induces TRPC5 ion channel activity and cytoskeletal remodeling in podocytes. Whether TRPC5 activity mediates FSGS onset and progression is unknown. We identified a small molecule, AC1903, that specifically blocks TRPC5 channel activity in glomeruli of proteinuric rats. Chronic administration of AC1903 suppressed severe proteinuria and prevented podocyte loss in a transgenic rat model of FSGS. AC1903 also provided therapeutic benefit in a rat model of hypertensive proteinuric kidney disease. These data indicate that TRPC5 activity drives disease and that TRPC5 inhibitors may be valuable for the treatment of progressive kidney diseases.National Institutes of Health (U.S.) (Grant DK095045)National Institutes of Health (U.S.) (Grant DK099465)National Institutes of Health (U.S.) (Grant DK103658)National Institutes of Health (U.S.) (Grant DK083511)National Institutes of Health (U.S.) (Grant DK093746

Restricted home ranges reduce children’s opportunities to connect to nature: demographic, environmental and parental influences

While many studies have documented the decline in the extent of children’s independent movements, none have explicitly evaluated the impact of this change in behaviour on opportunities to connect with nature. We estimate and compare the biodiversity values within urban children’s home ranges, and relate exposure to biodiversity to children’s perceptions and use of their neighbourhoods. We interviewed 178 children aged 9–11 years in three New Zealand cities. While children often had biodiverse areas present within 500 m of their home, their restricted home range size meant many of these natural areas fell outside of the range of their daily movements. Children’s declining independent mobility, strongly influenced by parental restrictions, appears to limit their freedom to use diverse and natural habitats within their urban neighbourhood, with use instead focused on private gardens and formal greenspaces. Development of a connection to nature in urban areas must therefore take place primarily in private gardens, which are threatened by urban planning approaches that promote dense residential developments with public rather than private greenspace