Short-term fasting before living kidney donation has an immune-modulatory effect.
Oudmaijer, C. A. J., et al.Frontiers in Immunology 2025; 16: 1488324.
Aims
To determine whether 48-h short-term fasting (STF) before elective donor nephrectomy alters the abundance and activation phenotype of circulating immune-cell subsets (T, B, dendritic and myeloid cells) in healthy living-kidney donors, a sub-study of the FAST randomised trial.
Interventions
Participants were randomised to control who had normal diet until standard midnight cut-off (mean fasting duration of 12 hours) or STF which consisted of < 250 kcal day⁻¹ (tea, clear soup) for 2 days and water only for final 24 h (mean fasting duration of 61 hours).
Participants
Adults accepted as living kidney donors, already randomised to either diet in FAST who have consented to extra blood analysis for immunomodulatory study. They analysed 22/30 consecutive donors (13 control, 9 STF). Eight omitted owing to missing peri-operative samples or cancelled surgery.
Outcomes
Absolute and relative frequencies of > 30 immune-cell subsets; activation markers (CD28, CD40, CD86, PD-1, HLA-DR) assessed using 3 multicolour flow-cytometry panels on cryopreserved PBMCs. Participant metabolic adherence was assessed with glucose, insulin and β-hydroxy-butyrate serum levels. They also performed an exploratory whole-blood RNA-seq pathway analysis.
Follow-up
6 weeks post-donation
CET Conclusions
The authors present a sub-study of the FAST RCT, “short-term fasting to improve outcomes in living kidney donation/transplantation” in which they scrutinise the immunomodulatory effects of short-term fasting (STF) prior to donation. A conceptually interesting study which found STF produced clear metabolic ketosis (lower glucose, lower insulin and increase BHB). Immunologically, after around 40 hours fasting donors showed: reduction in total CD4⁺ and CD8⁺ T cells, reduction in T-regulatory cells and activation markers, a reduction in central-memory T cells (CD4 & CD8) at surgery, with an increase in naïve / PD-1⁺ / HLA-DR⁺ B cells and an increase in cross-presenting cDC1 dendritic cells. These differences largely normalised after re-feeding except for persistently lower T-regs and higher NK-cell numbers in controls. This was however a small subset (n=22) of a larger trial not specifically designed or powered to scrutinise immunomodulatory effects or for clinically relevant outcomes as a result of these effects in the recipient. Their data suggest STF tilts the peri-operative immune milieu towards fewer activated / memory T cells and more naïve B cells and cDC1s, consistent with a transient “immune reset”. Whether this translates into reduced peri-operative inflammation, better graft function or altered infection risk is unknown. Findings are hypothesis-generating for larger trials assessing clinical end-points (IRI markers, donor recovery, recipient outcomes). They have demonstrated a 48-h very-low-calorie fast is feasible for healthy kidney donors and produces measurable, but reversible, immunomodulation. Incorporating STF as nutritional pre-conditioning merits further study, yet routine clinical adoption awaits confirmation of tangible clinical benefit.
Trial registration
Netherlands Trial Register - NL9262; EudraCT - 2020-005445-16