Exploratory findings from a German study suggest short-term calorie restriction in living kidney donors promotes molecular changes linked to organ protection, including dampened insulin signaling and reduced inflammation.
Previous animal studies have shown that calorie restriction protects kidneys from ischemia-reperfusion injury, a key factor in transplant outcomes. To explore the mechanisms in humans, researchers assigned 12 donors to either a 50% calorie-restricted or ad libitum diet for seven days before donation.
Biosamples from kidney biopsies, blood, urine, renal arteries, and perirenal fat were analyzed. Results showed reduced insulin signaling and inflammatory markers, notably CD44 (log2FC: −4.67) and COLEC11 (log2FC: −3.8). Lower levels of IGFBP3 and IGF2 indicated reduced insulin-like growth factor signaling. Ureter tissue also showed decreased growth factors, chemokines, and pro-inflammatory interleukins. Lipidomic analysis revealed nine of ten most downregulated metabolites in perirenal fat were triacylglycerides.
Despite its limited sample size, the study demonstrates the feasibility of a seven-day, 50% calorie restriction in living kidney donors, inducing molecular changes associated with organ protection such as reduced insulin signaling, triglyceride metabolism, and immune tolerance. The authors call for larger studies to confirm whether these changes improve clinical outcomes for donors and recipients.