GOFARR Laboratory, Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, Los Angeles, CA 90027, USA.
Division of Nephrology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Sci Transl Med. 2024 Oct 30;16(771):eadl5514. doi: 10.1126/scitranslmed.adl5514.
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.
断食模拟饮食（FMD）周期可促进老鼠的胰腺、血液、肠道和神经系统的再生和减少损伤，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动物相比，一种新开发的低盐 FMD（LS-FMD）周期可恢复嘌呤霉素诱导的肾病大鼠的正常蛋白尿和肾小球结构和功能。LS-FMD 诱导了肾发生基因程序的调节，类似于多种肾脏结构中的肾脏发育过程。LS-FMD 还激活了足细胞谱系重编程途径，并促进了大鼠肾脏损伤模型中成熟足细胞的静止状态。在一项针对慢性肾脏病患者的临床试验中，每月进行 5 天的 FMD 周期，持续 3 个月，与未接受 FMD 周期的患者相比，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 周期可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，应进一步测试其治疗进行性肾脏疾病的效果。
