the First Affiliated Hospital of Sun Yat-Sen University

Dual kidney transplantation (DKT) from small pediatric donors, either en-bloc or split dual kidney transplantation, contributes to mitigating organ scarcity. This study investigates the prognosis of DKT from pediatric deceased donors, and influencing factors.

A retrospective study included recipients who underwent DKT from pediatric donors between 2012 and 2022. Recipients were categorized into low mismatch (BWLM, n = 30) and high mismatch (BWHM, n = 10) groups based on donor-recipient weight ratio of 1:10. Outcome encompassed recipient and graft survival, renal function, and adverse events.

Forty recipients were included. The average follow-up period was 54.6 months. The 1, 3, and 5-year patient survival were 97.4%, with no significant differences between en-bloc and split dual kidney transplantation or between BWLM and BWHM groups. The graft survival at 1, 3, and 5 years were 89.9%, the graft survival of BWHM group was lower than BWLM group (70% vs 96.7%, p = 0.039). The average eGFR at 1, 3, and 5 years postoperatively were (78.93 ± 25.23), (83.82 ± 32.4), and (85.92 ± 37.08) mL/min/1.73 m², respectively. The BWHM group also experienced higher rates of graft-related surgical complications (p = 0.006) and urinary tract surgical complications (p = 0.042).

DKT from pediatric donors yields favorable outcomes, with similar graft survival and complication rates across surgical subgroups. However, significant donor-recipient weight mismatch, particularly when the ratio is less than 1:10, may contribute to increased surgical complications and poorer graft survival. Efforts to minimize extreme weight mismatch are recommended to optimize outcomes.

JOURNAL/nrgr/04.03/01300535-202511000-00030/figure1/v/2024-12-20T164640Z/r/image-tiff We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury. While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function, their precise function in spinal cord injury remains unclear. To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury, we conducted single-cell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury. Subsequently, we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16–17 days and extracted exosomes. The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes. Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs, 104 long non-coding RNAs, 720 circular RNAs, and 14 microRNAs compared with the control group. Construction of a competing endogenous RNA network identified the following hub genes: tuberous sclerosis 2 (Tsc2), solute carrier family 16 member 3 (Slc16a3), and forkhead box protein P1 (Foxp1). Notably, a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury. TSC2-positive cells were localized around SRY-box transcription factor 2–positive cells within the injury zone. Furthermore, in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells. Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways. In addition, Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways. Collectively, these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.