An in-depth analysis of the molecular changes induced by short-term calorie restriction before living kidney donation

Area of Science:

• Gerontology and Regenerative Medicine
• Transplant Immunology
• Metabolic Research

Background:

• Aging diminishes cellular resilience, increasing susceptibility to organ injury, particularly acute kidney injury (AKI).
• Ischemia-reperfusion injury (IRI) significantly impacts outcomes in kidney transplantation.
• While short-term calorie restriction (CR) shows promise in animal models for kidney protection against IRI, its human mechanistic insights remain limited.

Purpose of the Study:

• To investigate the clinical and molecular effects of short-term CR in living kidney donors prior to organ donation.
• To assess the feasibility and safety of a pre-donation CR intervention.
• To explore CR-induced molecular changes in donor tissues and their potential organ-protective mechanisms.

Main Methods:

• A randomized controlled trial involving 12 living kidney donors, assigned to either CR or an ad libitum diet for seven days pre-donation.
• CR participants consumed a formula diet at 50% of individual caloric needs.
• Collection and analysis of clinical parameters and biosamples (perirenal fat, renal arteries, ureters, kidney biopsies, blood, urine).

Main Results:

• Short-term CR was well-tolerated, leading to significant weight loss without increasing adverse events or affecting AKI incidence.
• Lipidomic and proteomic analyses revealed enhanced lipolysis and proteostasis, reduced insulin signaling, and decreased inflammatory factors in donor arteries and ureter tissue.
• Observed sex-specific molecular effects warrant further investigation.

Conclusions:

• Short-term CR is a feasible and safe intervention for living kidney donors.
• CR may promote organ protection in humans by modulating insulin signaling and inflammation.
• Findings provide a foundation for future research into CR-based interventions in clinical and transplant settings.