Kidney Week

Abstract: FR-PO1189

Less Is More: Protective Effects of Caloric Restriction on Acute and Chronic Kidney Injury

Session Information

• CKD: Mechanisms - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Molinari, Paolo, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy

Paolo Molinari, MD

• Verlato, Alberto, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Alberto Verlato, PhD

• Noble, Johan, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Johan Noble

• Alibrandi, Sara, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Sara Alibrandi, MD

• Alfieri, Carlo, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy

Carlo Alfieri, MD

• Castellano, Giuseppe, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy

Giuseppe Castellano, MD, PhD

• Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States

Paolo Cravedi, MD, PhD

Background

Acute kidney injury (AKI) leads to an high risk of progression to chronic kidney disease (CKD). Monocytes are crucial in renal injury pathogenesis, and caloric restriction appears to inhibit the CCL2/CCR2 axis and monocyte recruitment. Thus, we hypothesized that caloric restriction via a fasting-mimicking diet (FMD) reduces both acute and chronic kidney injury.

Methods

We compared the effects of FMD (5 days of caloric restriction and 2 days of ad libitum (ad lib)) vs. ad lib diet on the severity of aristolochic acid (AA)-induced AKI and kidney recovery in BALB/c male mice. Samples were collected after 2 days of normal diet in FMD mice.

Results

At 14 (AKI phase) and 35 (CKD phase) days post-injury, serum creatinine levels were significantly lower in mice on FMD (Figure 1A). Importantly, the protective effects of FMD on CKD were present also when FMD was started at the peak of AKI severity (14 days).
Overall, kidney infiltrating monocytes were reduced in FMD mice both at 14 and 35 days. Especially during transition from AKI to CKD (35 days), kidney monocyte infiltrates were markedly reduced by FMD, showing a clear shift towards Ly6c^low anti-inflammatory monocytes (Figure 1B). FMD markedly inhibited CCL2/CCR2 axis, leading to lower serum CCL2 levels and lower monocyte recruitment throughout kidney damage progression (Figure 1C). In the presence of a selective CCR2 inhibitor, FMD had no additional effects on kidney function, monocyte recruitment and infiltrating kidney monocytes indicating the key involvement of CCL2/CCR2 signaling in FMD's mechanism of action (Figure 1D).

Conclusion

FMD appears to mitigate acute and chronic kidney injury by decreasing CCL2-mediated recruitment of pro-inflammatory monocytes in the kidney.

Figure 1: FMD reduces renal damage and kidney monocyte infiltrates inhibiting CCL2/CCR2 axis.

Funding

• NIDDK Support