Failing kidney function is a serious issue for many older people, and at this time comparatively little can be done about it:
Chronic kidney disease (CKD) affects at least one in four Americans who are older than 60 and can significantly shorten lifespan. Yet the few available drugs for CKD can only modestly delay the disease's progress towards kidney failure. [Researchers] focused on a central feature of CKD: the "fibrosis" process. This is a pathological response to chronic kidney stress that includes an abnormal buildup of fibrous collagen, a loss of capillaries a die-off of important kidney cells called tubular epithelial cells, and other changes that progressively reduce a kidney's ability to filter the blood properly.
The researchers compared the patterns of gene activity in fibrotic and normal human kidney tissue samples. They found abnormal patterns in gene networks linked to inflammation and sharp drops in activity in gene networks that support energy metabolism in the fibrotic samples. The fact that inflammation is a factor in CKD was already well known, so [researchers]] aimed their investigation at two types of energy metabolism - glucose oxidation and fatty acid oxidation - that seemed markedly reduced in the fibrotic samples. "What we found is that the tubular epithelial cells preferentially use fatty acid oxidation as their energy source in normal conditions. Even when fatty acid metabolism drops in the context of CKD, these cells don't switch to burning glucose for energy."
In human tubular epithelial cells, artificially reducing fatty acid metabolism quickly brought about fibrosis-like signs, including the buildup of fat molecules (unspent fuel) and the deaths of many affected cells. That fat buildup in kidney cells had been hypothesized to be a significant cause of cell death in CKD fibrosis, [but] the fat accumulation on its own had minimal impact. The more important factor in fibrosis was the loss of energy in the cells as fatty acid metabolism dropped. Researchers also found evidence that the shutdown of fatty acid metabolism in tubular epithelial cells is caused in large part by the growth factor TGFβ. This factor is known to promote fibrosis and has been linked to high blood glucose levels, high blood pressure, and inflammation - all triggers of CKD. "We hope to develop new compounds [that] boost enzymes more specifically related to fatty acid metabolism. In that way we might be able to greatly slow the progress of CKD."