Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreases, blood, guts, and nervous systems of mice, but their effect on kidney disease is unknown. In addition, a FMD has not been tested in rats. Here, we show that cycles of a newly developed low-salt FMD (LS-FMD) restored normal proteinuria and nephron structure and function in rats with puromycin-induced nephrosis compared with that in animals with renal damage that did not receive the dietary intervention. LS-FMD induced modulation of a nephrogenic gene program, resembling renal developmental processes in multiple kidney structures. LS-FMD also activated podocyte-lineage reprogramming pathways and promoted a quiescent state in mature podocytes in the rat kidney damage model. In a pilot clinical study in patients with chronic kidney disease, FMD cycles of 5 days each month for 3 months promoted renoprotection, including reduction of proteinuria and improved endothelial function, compared with that in patients who did not receive the FMD cycles. These results show that FMD cycles, which promote the reprogramming of multiple renal cell types and lead to glomerular damage reversal in rats, should be tested further for the treatment of progressive kidney diseases.

中文翻译：

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肾特异性模拟空腹饮食可诱导足细胞重编程并恢复肾小球病患者的肾功能


模拟禁食饮食 （FMD） 的周期可促进小鼠胰腺、血液、肠道和神经系统的再生并减少损伤，但它们对肾脏疾病的影响尚不清楚。此外，尚未在大鼠中测试 FMD。在这里，我们表明，与未接受饮食干预的肾损伤动物相比，新开发的低盐 FMD （LS-FMD） 的周期恢复了嘌呤霉素诱导的肾病大鼠的正常蛋白尿和肾单位结构和功能。LS-FMD 诱导了肾源基因程序的调节，类似于多个肾脏结构中的肾脏发育过程。LS-FMD 还激活足细胞谱系重编程途径，并在大鼠肾损伤模型中促进成熟足细胞的静止状态。在一项针对慢性肾病患者的初步临床研究中，与未接受 FMD 周期的患者相比，每月 5 天、持续 3 个月的 FMD 周期可促进肾脏保护，包括减少蛋白尿和改善内皮功能。这些结果表明，FMD 周期促进多种肾细胞类型的重编程并导致大鼠肾小球损伤逆转，应进一步测试用于治疗进行性肾病。