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Abstract: FR-OR107

Fasting-Mimicking Diet and Podocyte Protection

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Perin, Laura, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Villani, Valentina, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Nicolas Frank, Camille H., Harvard Medical School, Boston, Massachusetts, United States
  • Hou, Xiaogang, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Da Sacco, Stefano, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Lemley, Kevin V., Children's Hospital Los Angeles, Los Angeles, California, United States
  • Lai, Silvia, Universita degli Studi di Roma La Sapienza, Rome, Lazio, Italy
  • Laviano, Alessandro, Universita degli Studi di Roma La Sapienza, Rome, Lazio, Italy
Background

Dietary management is of particular importance in the context of kidney disease. Our data indicate that periodic cycles of a fasting-mimicking diet (FDM) can ameliorate kidney damage by preventing podocyte loss. Using different tools and animal models, we showed the renoprotection of the FDM in the contest of glomerulopathies. We also showed, in a small pilot clinical trial that FMD is safe, feasible, and potentially beneficial to patients with CKD.

Methods

Damage in rats was established by puromycin (PAN). Rats were fed with six cycles of FMD or ad-lib. Morphological, physiological, and spatial transcriptomics (ST) data were collected at long term. Early molecular changes induced by the FMD were studied by snRNA-seq after one cycle. We used our Alport-podocyte-FUCCI (Fluorescence Ubiquitin Cell Cycle Indicator) mice to study the podocyte cell cycle. We administered 3 cycles of FMD to a small cohort of 13 patients (9 men and 5 women, 38-63 years) with stage III CKD.

Results

FMD downregulated proteinuria, ameliorated glomerular sclerosis, and protected podocyte number. ST showed that ctrl and FMD-rats present very similar spatial gene maps vs the PAN-rats. snRNA-seq showed that in PAN-rat, the FMD activated podocyte-specification genes, revealing the important role of fasting followed by refeeding in inducing transcriptional changes in podocytes after damage. In the Alport-podocyte-FUCCI mice, FMD lowered the podocyte number in G1 and increased the podocyte number in G0. In CKD patients, FMD downregulated IGF1, protein C, proteinuria, epicardial fat, and upregulated flow-mediated dilation value (indicating amelioration of endothelial function).

Conclusion

These results indicate that FMD promotes the maintenance of glomerular structure and function by inducing podocyte repair and by preserving the G0 state in these cells. FMD cycles could represent a potential treatment for patients affected by progressive kidney disease.