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Abstract: SA-PO813

Cycles of a Fasting Mimicking Diet Restore Renal Function in a Rat Model of PAN Nephrosis

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

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., The Saban Research Institute, Los Angeles, California, United States
  • Buono, Roberta, USC, Los Angeles, California, United States
  • Dedhia, Charmi, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Longo, Valter, USC, Los Angeles, California, United States
Background

A major hallmark of end-stage renal disease (ESRD) is the irreversible loss of the glomerular filtration barrier, the structure in charge of the blood ultrafiltration. The only treatment options for ESRD are dialysis or transplantation. To date, no cure is available to restore kidney function in ESRD patients. While dietary recommendations are currently given to patients with kidney disease to minimize the burden of the disease itself and slow down its progression, no diet has proven effective in restoring renal function. Animals have evolved adaptive mechanisms to fasting that are associated with stress resistance, reduced inflammation, longer lifespan. The fasting mimicking diet (FMD) was developed to induce similar metabolic changes as observed during fasting and FMD has been clinically proven to be extremely efficient in various human disease settings (including diabetes and cancer) by activating endogenous regenerative mechanisms.

Methods

We tested the potential of FMD to treat kidney disease. Sprague Dawley rats were injected with puromycin aminonucleoside (PAN) to induce chronic nephrosis. Multiple cycles of FMD have been applied to PAN-induced rats to determine their effect on renal function and structure. Rats were monitored for renal physiological parameters, histological and WB analysis of glomerular and tubular structures were performed.

Results

We observed amelioration of proteinuria and reduced levels of BUN in rats undergoing 6 cycles of FMD compared to the PAN group. The effect was sustained long term up to 6 weeks after the last dietary cycle. Histological characterization showed preservation of the renal structure including tubular and glomerular structures in rats treated with FMD in contrast to PAN-induced rats. Podocyte number in FMD treated rats was comparable with that of healthy animals, while a significant reduction was noted in the PAN group. WB also revealed mitochondrial function protection measured by the level of mtTFA protein expression (mitochondrial transcription factor A) associated with the post re-feeding time after only one cycle of diet.

Conclusion

These results support the application of multiple cycles of FMD to restore renal function and as a possible treatment of chronic kidney disease .

Funding

  • Private Foundation Support