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Immune Regulatory Signatures Associated with Different Recovery Durations of Delayed Graft Function after Kidney Transplantation.

Delayed graft function (DGF) is a common early complication of kidney transplantation characterized by immune activation. The duration of DGF may significantly affect long-term graft survival, yet the immune mechanisms underlying the different DGF durations remain unclear. Using a functional definition of delayed graft function (fDGF), defined as a failure of serum creatinine to decrease by at least 10% per day for three consecutive days within the first postoperative week, patients were stratified into short-term DGF (SDGF) and long-term DGF (LDGF) groups according to recovery periods. In this exploratory study, targeted proteomic analysis indicated that proteins enriched in SDGF were primarily involved in innate immune responses and acute inflammatory processes, including neutrophil chemotaxis and migration, whereas LDGF exhibited features related to adaptive immune responses and chronic inflammation, such as T-cell differentiation and activation. IL-7 and CCL20 were identified as candidate molecules potentially associated with different DGF durations. Targeted metabolomics revealed disturbances in amino acid metabolism, particularly alanine, aspartate, and glutamate metabolism, as well as in energy metabolism, including the tricarboxylic acid (TCA) cycle, which may be involved in LDGF. These findings provide preliminary insights into immune metabolic features associated with different DGF recovery durations.

Humans

Should we consider excessive weights in pediatric kidney transplant recepient candidates?: A systematic review and meta-analysis of kidney transplantation outcomes.

INTRODUCTION: In adult populations, excess body weight has been associated with an increased risk of adverse clinical outcomes and mortality following kidney transplantation. In contrast, the influence of obesity on transplantation outcomes among pediatric populations is not yet fully understood. This study aimed to evaluate the association between pre-transplant excess weight and post-transplant outcomes in pediatric kidney transplant recipients. MATERIAL & METHODS: A systematic literature search was performed across PubMed, ScienceDirect, and the Cochrane Library, covering publications up to December 31, 2025. The quality of the included studies was evaluated using the ROBINS-E tool. Statistical analysis was conducted using Review Manager version 5.4. RESULTS: From a total of 1465 records screened, six studies that included 65,483 participants were selected in the meta-analysis. The results indicated that pre-transplant excess weight was significantly associated with an increased risk of acute rejection (OR = 1.09; P = 0.009), delayed graft function (OR = 1.17; P < 0.00001), 1-year graft failure (OR = 1.16; P = 0.0002), and 5-year graft failure (OR = 1.13; P = 0.009). Although 5-year mortality was also higher among recipients with excess weight, this association was not statistically significant (OR = 1.08; P = 0.11). CONCLUSION: Pediatric patients with pre-transplant excess weight had higher post-transplant odds of acute rejection, delayed graft function, and both 1-year and 5-year graft failure compared to those without excess weight. These findings highlight the importance of assessing and managing excess weight prior to kidney transplantation to help prevent adverse outcomes in the future.

Humans

Urine-Derived Cells in Kidney Transplantation: Linking Cellular Phenotypes, Secretome Signatures and Multi-Omic Technologies.

Kidney transplant monitoring and early identification of graft dysfunction are central needs for long-term graft survival. Although kidney biopsy represents the gold standard in diagnostic procedures, its invasiveness may limit frequent longitudinal evaluation, highlighting the necessity of non-invasive diagnostic tools. Urine has emerged over the years as an easily obtainable source of cellular and molecular components derived from transplanted kidneys. Particularly, exfoliated cells and extracellular vesicles (EVs) represent complementary and interconnected markers able to reflect tissue injury, inflammatory signals, immune cell infiltration, and regenerative processes occurring in the graft. Also, recent advances in transcriptomics, proteomics, metabolomics, and single-cell technologies have expanded the diagnostic and mechanistic value of urinary liquid biopsy, enabling the identification of disease-specific molecular signatures associated with rejection, delayed graft function, fibrosis, and graft loss. This review discusses the emerging concept of an integrated urinary cell-EV ecosystem and highlights how integrated multi-omic approaches may transform non-invasive graft surveillance and advance precision medicine in kidney transplantation.

Humans

Long-term functional synaptic integration of genome-edited retinal organoids in a primate model of macular degeneration.

Retinal organoids represent a promising regenerative strategy for restoring vision in retinal degenerative diseases, but the capacity of host cone bipolar cells in the primate macula to rewire with transplanted photoreceptors has not been established. In this study, we transplanted genome-edited ISL1-/- human retinal organoids lacking ON-bipolar cells into an acute laser-induced macular photoreceptor ablation non-human primate model. Using immunohistochemistry, ultrastructural imaging, and focal macular electroretinography, we demonstrate that host rod and cone bipolar cells actively extend dendrites toward grafted photoreceptors and form synaptic contacts, with evidence of functional signal transmission in a subset of transplanted eyes. Longitudinal, per-eye analyses revealed that host ON-bipolar responses improved in two of four eyes with ISL1-/- graft by up to 21.6% and remained stable for up to 2 years post transplantation. Moreover, OFF-pathway connectivity showed potential progressive maturation, with delayed increase in d-wave after 13 months in one of those eyes. These findings provide the first demonstration of long-term anatomical host-graft synaptic integration in the primate macula, establishing that central cone bipolar circuits retain the capacity for durable rewiring with human stem-cell-derived grafts. Our results highlight ISL1-/- retinal organoids as a promising approach for central vision restoration in macular degeneration.

Animals