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.  In a pilot randomized cross-over study in patients with chronic kidney disease, FMD cycles promote renoprotection by reducing proteinuria and improving endothelial function. These results show that LS-FMD cycles, which promote the reprogramming of multiple renal cell types, leading to glomerular damage reversal, should be tested further in the treatment of progressive kidney diseases. Overall design: Sprague-Dawley rats were injected with puromycin aminonucleoside. A group of rats (N=3) were analyzed at 14 days (PAN), another group were subjected to one cycle (4 days) of low salts fasting-mimicking diet (LS-FMD) and analyzed at end of diet (EoD, and at 24 hours and 72 hours after re-feeding with regular chow (N=3 each group). A group of N=4 halthy rats were included as baseline controls in the analysis.