Daijiworld Media Network - New Delhi

New Delhi, Jun 4: A new exploratory study has suggested that a short period of calorie restriction (CR) before kidney donation may trigger molecular changes associated with organ protection and improved stress resistance in living kidney donors.

Previous animal studies have shown that calorie restriction can protect kidneys from ischemia-reperfusion injury — a form of tissue damage that occurs when blood supply returns to an organ after a period of interruption and can significantly influence kidney transplant outcomes. However, evidence in humans has remained limited.

In the study, researchers evaluated 12 living kidney donors who were assigned either a calorie-restricted diet or a normal unrestricted diet. Participants in the calorie restriction group reduced their caloric intake by 50 per cent for seven days before donation.

Researchers analysed biological samples including kidney biopsies, blood, urine, renal arteries and perirenal fat tissue to assess the effects of the dietary intervention.

The findings showed that calorie restriction was associated with reduced insulin signalling and lower levels of inflammatory factors, while enhancing lipolysis, or fat breakdown, in donor arteries and ureter tissue.

Among the most significantly altered biomarkers were inflammatory markers such as CD44 and COLEC11, both of which showed substantial reductions. Researchers also observed lower levels of insulin-like growth factor-related proteins, including IGFBP3 and IGF2, indicating reduced insulin-like growth factor signalling.

Analysis of ureter tissue revealed decreased concentrations of growth factors, chemokines, immune-response regulators, pro-inflammatory interleukins and endothelial adhesion molecules among participants who underwent calorie restriction.

In addition, lipidomic analysis of perirenal fat demonstrated significant metabolic changes. Nine of the ten most strongly reduced metabolites were identified as triacylglycerides, suggesting increased utilisation of stored fat reserves.

Researchers noted that these molecular changes may contribute to protective mechanisms such as reduced inflammation, improved metabolic adaptation and enhanced immune tolerance.

However, the study's authors cautioned that the findings should be interpreted carefully due to the small sample size. They described the research as exploratory and emphasised that its applicability to elderly, multimorbid or deceased organ donors remains uncertain because the study focused exclusively on healthy living kidney donors.

The researchers concluded that a seven-day period of 50 per cent calorie restriction appears feasible for living kidney donors and may induce biological changes linked to organ protection.

While the findings provide valuable insight into potential mechanisms behind calorie restriction-induced stress resistance, larger clinical studies will be required to determine whether these molecular effects translate into better outcomes for kidney donors and transplant recipients.

The authors also called for future research to examine sex-specific responses to calorie restriction and to assess whether the observed benefits can be replicated across broader donor populations.