Immune cell dynamics during compensatory renal hypertrophy after unilateral nephrectomy

The mechanisms underlying compensatory renal hypertrophy (CRH) in living kidney donors after unilateral nephrectomy (UNx) remain complex and underexplored. We examined immune cells involved in CRH after UNx in mice. Following UNx of the left kidney in WT mice, GFR measurements, flow cytometry, and single-cell RNA-seq were performed over an 8 wks period. Rag1 −/− mice were studied to explore the role of adaptive immune cells in GFR changes during CRH. Immune cells showed dynamic, time-dependent changes after UNx. The innate immune system responded rapidly, with increases in neutrophils and macrophages, while NK cells initially decreased. Subsequently, adaptive immune cells, including CD4⁺, CD8⁺, and DN-T cells, showed changes in activation/resident marker CD69 and regulatory markers such as CD4⁺CD25⁺. Expression of PD-1, CTLA-4, and TIGIT on T cells changed during acute injury (0–24 hrs), recovery phase (24 hrs -1 wk), and late adaptation (4–8 wks). GFR was significantly higher in the later recovery phase in Rag1 −/− mice than in WT mice. These findings demonstrate multi-phase dynamic immune cell changes in remnant kidney after UNx, characterized by rapid innate immune cell activation, gradual adaptive immune cell regulation, and shifts in immune checkpoint levels. These immune changes could influence compensatory changes in the remnant kidney in live kidney donors and other patients with a uninephrectomy.