A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreas, blood, gut, and nervous systems of mice but its effect on kidney disease is unknown, and the FMD has not been tested in rats. Here we show that cycles of a newly developed low-salt FMD (LS-FMD) restore normal proteinuria, nephron structure and function in rats with puromycin-induced nephrosis in the long term. LS-FMD induces expression of nephrogenic markers, resembling renal developmental processes in multiple kidney structures, and activates podocyte-lineage reprogramming pathways, in addition to promoting a quiescent state in mature podocytes. Sprague-Dawley rats were injected with puromycin aminonucleoside. Rats were either fed ad libitum, or a low salts fasting mimicking diet (LS-FMD). A group of healhty rats was used as control. Rats were fed a total of 6 cycles of diet and analyzed 6 weeks post treatment after 5 months from the PAN injection. Another healthy rat was fed one cycle of LS-FMD and analyzed at 72 hours post refeeding. Kidneys were harvested, embedded in OCT and frozen. 10 um sections were cut and laid on a gene expression slide for Visium spatial transcriptomics.