Helong Dai

Kidney transplantation is the optimal treatment for end-stage kidney disease (ESKD), but transplant-associated acute kidney injury (AKI), primarily driven by ischemia–reperfusion injury (IRI), contributes to delayed graft function (DGF) and inferior long-term graft outcomes. Rodent kidney transplantation models provide a clinically relevant platform. This review summarizes the establishment and application of rat and mouse kidney transplantation models for studying transplant-associated acute kidney injury. It highlights critical variables in model design, including surgical techniques, ischemic conditions, organ preservation, donor characteristics, and immunological settings that influence experimental outcomes. It further synthesizes current mechanistic evidence on oxidative stress, microvascular injury, immune activation, regulated cell death, tissue repair and fibrosis, molecular regulatory networks, multi-omics analyses, and remote organ injury. The review also examines interventions targeting donor conditioning, organ preservation and perfusion, reperfusion inflammation, recipient therapy, and regenerative repair, while considering their experimental limitations and translational relevance. Rodent kidney transplantation models can bridge conventional renal ischemia–reperfusion models and clinical transplantation. Future progress will depend on standardized surgical procedure, clinically relevant model selection, rigorous long-term outcome assessment, and the integration of emerging molecular technologies to enhance translational relevance.

Acute kidney injury (AKI) is a critical clinical syndrome, with sepsis being a major trigger associated with high mortality, making early intervention crucial. Ethyl caffeate (EC), a natural phenolic compound, exhibits anti-inflammatory, antioxidant, and immunomodulatory activities. However, its role and underlying mechanisms in sepsis-associated AKI (SA-AKI) remain unclear. This study investigated the renoprotective effects and mechanisms of EC using a lipopolysaccharide (LPS)-induced murine AKI model. We found that EC pretreatment significantly reduced the LPS-induced elevations in serum creatinine and blood urea nitrogen levels, alleviated histopathological renal damage, and downregulated the expression of injury biomarkers KIM-1 and NGAL. EC also suppressed the expression of renal and systemic inflammatory factors (e.g., IL-6, IL-18) and inhibited caspase-1 activation. Further mechanistic investigations demonstrated that EC restrains macrophage polarization toward the pro-inflammatory M1 phenotype by suppressing the JAK1-STAT1 signaling pathway. Concurrently, EC promotes apoptosis of M1 macrophages through inhibition of the PI3K/AKT-Bcl-2 survival axis, thereby accelerating the resolution of inflammation. In summary, ethyl caffeate alleviates LPS-induced acute kidney injury through dual regulation of macrophage polarization and apoptosis, involving the inhibition of JAK1-STAT1 and PI3K/AKT signaling pathways. This study provides new experimental evidence supporting EC and its analogs as a potential strategy for AKI intervention.

Interleukin‐27 (IL‐27) is a multifunctional cytokine produced mainly by innate immune cells that regulates immune responses primarily through the Janus kinase (JAK)‐signal transducer and activator of transcription (STAT) signaling pathway. The role of IL‐27 in immune regulation is complex and often paradoxical, with both pro‐inflammatory and immunosuppressive functions described, depending on the specific immune context and cellular milieu. Here, we systematically discuss the dual regulatory roles of IL‐27 in immune regulation, with a particular emphasis on its role in the JAK‐STAT signaling pathway. We highlight the latest advancements in understanding the functional differences and molecular mechanisms of IL‐27 in both adaptive and innate immune cells. We further elaborate on IL‐27‐mediated immune regulation through nonimmune cells. Understanding the multifaceted and context‐dependent properties of IL‐27 is essential for deciphering the precise role of IL‐27 in health and disease and for developing targeted immunotherapies. This review systematically analyzes the “double‐edged sword” mechanism of IL‐27, providing a theoretical and translational basis for targeting the JAK‐STAT pathway.

Background: Sepsis-associated acute kidney injury (SA-AKI) drives high mortality in sepsis. The triggering receptor expressed on myeloid cells-1 (TREM1) plays critical roles in both infectious and non-infectious pathologies. However, the role of TREM1 in AKI still needs to be further clarified. Methods: Using both in vivo and in vitro experiments, we examined the role and underlying mechanism of TREM1 in AKI. Results: In this study, the level of soluble TREM (sTREM1) in the urine of patients with SA-AKI was significantly higher than that of the healthy control group, although there was no significant difference in sTREM1 levels in the serum. In the SA-AKI mouse model, TREM1 deficiency markedly reduced serum creatinine levels in SA-AKI mice. Notably, TREM1 deficiency significantly promoted the expression levels of Il10 and Cd206 in the kidneys of SA-AKI mice. Cytometric Bead Array analysis revealed that serum levels of the pro-inflammatory cytokines IL17A and IFN-γ were significantly diminished, whereas the anti-inflammatory factor IL10 was notably elevated. The enzyme-linked immunosorbent assay (ELISA) results showed that the serum levels of CCL2 and CXCL1 in TREM1-deficient mice were significantly reduced. Mechanistically, experimental evidence indicated that TREM1 deficiency promoted M2 macrophage polarization by activating IRF4 via PI3K/AKT and STAT6 pathways. Conclusions: These findings confirmed that TREM1 is the primary regulatory factor of macrophage plasticity in SA-AKI, proposing a therapeutic strategy for the clinical intervention of SA-AKI-related kidney diseases.

Purpose: While fluid intake and trace elements are known to influence kidney stone risk, the impact of drinking water type remains unclear. This study aimed to systematically evaluate the association between water source and kidney stone prevalence. Methods: This analysis included 10 246 adults (≥20 years) from the National Health and Nutrition Examination Survey database (2009–2016). Kidney stone history was self-reported, and drinking water sources were assessed through 24-hour dietary recalls. We employed multivariable-adjusted logistic regression models, adjusting for potential confounders including age, sex, race, body mass index (BMI), physical activity, calcium intake, smoking status, alcohol consumption, diabetes, and hypertension, to evaluate the association between drinking water type and kidney stone occurrence. To assess potential nonlinear relationships, restricted cubic spline (RCS) models were utilized. Additionally, cluster analysis was performed to categorize participants into distinct subgroups based on water consumption patterns. Finally, propensity score matching (PSM) and subgroup analyses were conducted to further validate the robustness of the findings. Results: Logistic regression suggested that higher tap water intake was significantly inversely related with kidney stone prevalence [adjusted odds ratio (OR) = 0.678, 95% confidence interval (CI): 0.491–0.938, P for trend = 0.0177], suggesting a 32% lower odds of kidney stones with increased tap water consumption. However, bottled water intake was not significantly associated with kidney stone risk. The RCS model revealed a linear decreasing trend between tap water intake and kidney stone risk ( P for all P for nonlinear = 0.8505). Cluster analysis showed that high tap water intake and low bottled water intake were associated with a lower prevalence of kidney stones. This association persisted in the propensity score-matched models and subgroup analyses after adjustment for bottled water intake. Conclusion: Our study revealed an inverse association between tap water intake and kidney stone prevalence among U.S. adults. Bottled water intake had no statistically significant effect on stone formation. These results suggest that higher tap water intake may confer a protective effect against kidney stone formation. These findings could guide public health recommendations on hydration habits.

Kidney transplantation is the optimal treatment for end-stage renal disease; however, the limited availability of donor kidneys hinders the advancement of this procedure. The utilisation of expanded criteria donor (ECD) kidneys and kidney donor profile index (KDPI) > 85% kidneys represents a significant initiative in addressing this shortage. Our study aimed to investigate the clinical outcomes of kidney transplantation by the ECD and KDPI > 85% kidneys, as well as the risk factors influencing graft survival, with the aim of providing a reference for the clinical application of the ECD and KDPI > 85% kidneys in Chinese population. This retrospective analysis included 326 adult donor kidney transplant recipients from July 2018 to June 2020. The donor kidneys were classified into ECD kidneys (n = 110) and standard criteria donor (SCD) kidneys (n = 216) based on the United Network for Organ Sharing (UNOS) criteria, as well as into kidneys with KDPI > 85% (n = 42) and KDPI ≤ 85% (n = 284), according to the donor’s KDPI value. T tests, chi-square tests, and Mann-Whitney U tests were used to compare complications and renal function following kidney transplantation. Additionally, the log-rank test was used to assess differences in survival rates, whereas Cox regression analysis was conducted to identify risk factors associated with graft loss. Analysis revealed that grafts from ECDs exhibited significantly poorer survival rates (P = 0.004), whereas the survival rates of their recipients were comparable (P = 0.710). No significant differences were observed between the ECD and SCD groups regarding the incidence of DGF (22.7% vs. 26.4%, respectively; P = 0.471) or AR (24.5% vs. 25.9%, respectively; P = 0.787). At 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years posttransplantation, the SCr level and eGFR in the ECD group were significantly lower than those in the SCD group (all P < 0.05); however, no differences were noted at 1 month posttransplantation. Furthermore, the SCr level and eGFR in the kidneys of patients with a KDPI > 85% were significantly worse than those in the kidneys of patients with a KDPI ≤ 85% at 6 months, 2 years, 3 years, and 4 years posttransplantation (all P < 0.05), with no differences being observed at 1 month, 3 months, and 1 year posttransplantation. Additionally, no significant differences were observed between the KDPI > 85% and KDPI ≤ 85% groups regarding the incidence of DGF, AR, graft survival, or recipient survival (all P > 0.05). Multivariate Cox regression analysis indicated that ECD kidneys (HR = 3.647, P = 0.003) and AR (HR = 4.675, P < 0.001) were independent risk factors for graft loss. In this validation study of the transplant scoring criteria based on the Chinese population, our study indicated that compared with SCD kidneys, ECD kidneys demonstrated poorer graft survival and a tendency towards inferior postoperative renal function. However, the rates of recipient survival, DGF, and AR were comparable. Additionally, graft and recipient survival, as well as the incidence of DGF and AR, in KDPI > 85% kidneys were also similar to those in KDPI ≤ 85% kidneys. Nevertheless, kidneys with a KDPI > 85% tended to exhibit inferior postoperative renal function. Thus, the KDPI score is a valuable tool for predicting graft function in Chinese population.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by multisystem involvement, primarily caused by loss-of-function mutations in the TSC1 or TSC2 genes. TSC is a key integrator of metabolic signaling and cellular stress and has become an important regulator in several kidney diseases. TSC1 and TSC2 can be used not only as genetic markers for disease diagnosis, but also as potential immunotherapeutic targets for kidney disease. Recent studies on the pathogenesis of TSC may provide guidance for developing new treatment strategies for kidney diseases. Therefore, we systematically reviewed the molecular biology of TSC and their signaling pathway, regulation of cell metabolism, and immune response in acute renal injury, chronic kidney disease, diabetic kidney disease, renal cysts, benign and malignant intrarenal tumors, and renal angiomyolipomas. We also summarize the efficacy and adverse effects of mTOR inhibitors in the treatment of TSC-related kidney diseases.

The exact mechanism of graft dysfunction has not been fully clarified. We aimed to explore the causal effects of serum metabolites on graft dysfunction and the mediating role of inflammatory proteins. We first analyzed the causal association of 1,091 serum metabolites and 91 inflammatory proteins with graft dysfunction by Mendelian randomization (MR) to find the most important indicators and calculated the mediating role of inflammatory proteins. Second, we further intergrated the single-cell analysis, machine learning, and Shapley Additive exPlanations (SHAP) methods to validate the role of the inflammatory protein in rejected transplanted kidneys. In MR analysis, the inverse variance weighted (IVW) method showed that N-acetylaspartyl glutamate (NAAG) levels reduced the risk of graft dysfunction (OR 0.648, 95% CI 0.522-0.805). Interleukin-2 receptor subunit beta (IL-2RB) mediated the association between NAAG and graft dysfunction with a mediation ratio of 11.35% (95% CI 1.85%-24.69%). In transplanted kidneys, IL-2RB is predominantly expressed elevated in T cells from rejection samples and is associated with decreased renal function. 10 hub genes were identified based on T cells with high and low expression of IL-2RB, of which NGboost reached AUC 0.77. The SHAP method obtained the gene with the greatest model contribution: the IL-2RB gene. NAAG plays a protective role in graft dysfunction, and part of the effect is mediated by inhibition of IL-2RB, which is verified as an important gene that functions in transplant kidney rejection. NAAG and IL-2RB may be novel molecular markers and therapeutic targets for graft dysfunction.