EXPLORATORY findings suggest that molecular changes associated with organ protection are promoted through the dampening of insulin signalling and inflammation when living kidney donors experience short-term calorie restriction (CR) according to a new German study.
Calorie Restriction in Kidney Donors
Previous studies have shown that CR in animals protects kidneys from ischemia-reperfusion injury which has a key influence kidney transplantation outcomes. However, translation to humans remains limited because the underlying mechanisms are not fully understood.
12 donors were either assigned a CR or ad libitum diet. CR entailed a 50% reduction in caloric intake for seven days prior to donation. Bio samples of kidney biopsies, blood, urine, renal arteries and perirenal fat were assessed.
Effects of Calorie Restriction
Results indicated that under CR for living kidney donors, there was reduced insulin signalling and inflammatory factors and enhance lipolysis in donor arteries and ureter tissue.
Among the most significantly altered factors were the inflammatory markers CD44 Most strongly changed were CD44 (log2FC: −4.67; p-value: 0.001), COLEC11 (log2FC: −3.8; p-value: 0.0017). Researchers also observed a decrease in the abundance of, IGFBP3 and IGF2 suggesting reduced insulin-like growth factor signalling (log2FC<−0.6; p-value: 0.01).
Ureter tissue also showed lower concentrations of growth factors, chemokines, immune response regulators pro-inflammatory interleukins and endothelial adhesion molecules in those who underwent CR.
Lipidomic analysis of perirenal fat revealed that nine out of ten of the most strongly downregulated metabolites were triacylglycerides.
Limitations
This study is considered exploratory in nature given its limited sample size. Moreover, the transferability of this study on kidney transplantations of those who are multimorbid, elderly or transplantations of those who are recently deceased is limited because this trial focused on CR in kidney donors before transplantations.
Conclusion
Overall, this exploratory study highlights the feasibility of a seven-day period of 50% CR on living kidney donors. The findings show that short term CR induces molecular changes associated with organ protection with protective mechanisms including reduced insulin signalling, metabolism of triglycerides and immune tolerance. While these findings provide insight into potential mechanisms of CR-induced stress resistance, larger studies are needed to determine whether these molecular changes translate into improved clinical outcomes for donors or transplant recipients.
Future Studies
The authors highlighted the need for larger studies to investigate sex-specific responses to CR and to determine whether the observed molecular changes improve transplant outcomes in broader donor populations.
Reference
Späth MR et al. An in-depth analysis of the molecular changes induced by short-term calorie restriction before living kidney donation. npj Aging. 2026;12:70.
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