To investigate the effects of renal tubular epithelial cell-specific c-kit gene knockout on macrophage infiltration and renal interstitial fibrosis following unilateral ischemia-reperfusion injury (uIRI) in mice.

Eight-week-old male renal tubular epithelial cell-specific c-kit knockout mice (Ggt1-Cre c-kit^-/-), c-kit^loxp/loxp mice, and wild-type (WT) C57BL/6J mice were used to establish the uIRI model. Experimental mice were divided into six groups (n= 12 per group): Ggt1-Cre c-kit^-/- uIRI group, c-kit^loxp/loxp uIRI group, C57BL/6J uIRI group (WT uIRI group), Ggt1-Cre c-kit^-/- sham group, c-kit^loxp/loxp sham group, and C57BL/6J sham group (WT sham group). Kidney tissue and blood samples were collected at 1, 3, 14, and 28 days post-operation. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured, and renal histopathological changes were evaluated. Sirius red staining was used to assess renal interstitial fibrosis. Macrophage infiltration was examined by immunohistochemistry. The protein and mRNA expression levels of α-smooth muscle actin (α-SMA), vimentin, and collagen I were detected by Western blotting and RT-qPCR, respectively. ANOVA software was used for statistical analysis.

Compared with the WT uIRI group and c-kit^loxp/loxp uIRI group, the Ggt1-Cre c-kit^-/- uIRI group exhibited significantly lower SCr and BUN levels at all time points after uIRI operation (all P<0.05). On 3 and 14 days post-operation, the number of infiltrating macrophages in the Ggt1-Cre c-kit^-/- uIRI group was significantly reduced compared with the other two uIRI groups. On postoperative day 28, the renal interstitial fibrosis score and the mRNA and protein expression levels of fibrosis markers (α-SMA, vimentin, and collagen I) in the Ggt1-Cre c-kit^-/- uIRI group were significantly lower than those in the other two uIRI groups (all P<0.05).

Renal tubular epithelial cell-specific c-kit gene knockout significantly attenuates renal interstitial fibrosis and inhibits macrophage infiltration, suggesting that c-kit gene may serve as a new therapeutic target for kidney diseases.

To explore the correlation between dynamic changes of serum complement C3 and C4 and renal function progression as well as prognosis in patients with lupus nephritis.

Patients with lupus nephritis diagnosed by renal biopsy between January 2022 and January 2025 were retrospectively enrolled. Clinical, pathological, and serum complement C3 and C4 data at baseline (Day 0) and all time points within the 0-180-day follow-up period were collected. The relative change amplitude and time-weighted mean of complement levels from Day 0 to Day 180 were calculated. Patients were classified into the persistently normal group, the recovered group, the persistently reduced group, and the newly reduced group according to complement levels at baseline and Day 180. Landmark analysis was performed with Day 180 as the landmark time point. The Kaplan-Meier method and multivariate Cox regression model were used, and LASSO-Cox regression was adopted for sensitivity analysis to assess the association between longitudinal changes in complement levels and the composite endpoint of renal function progression.

A total of 148 patients with lupus nephritis were enrolled in this study, with a median follow-up of 19.80 months. Among them, 32 patients (21.62%) developed renal function progression and were assigned to the progression group, and the remaining 116 patients were included in the non-progression group. Compared with the non-progression group, the progression group had lower baseline levels of complement C3 and C4 (all P<0.05). The proportion of patients with persistently reduced C3 and C4 in the progression group was higher than that in the non-progression group (all P<0.05). Patients with persistently reduced C3 and C4 exhibited the lowest renal progression-free rate (P<0.05). After adjustment for confounding factors, the persistently reduced C3 phenotype was independently associated with renal function progression (HR=3.120, 95%CI: 1.051-9.270, P=0.040). Indicators related to C4 showed no significant association with renal function progression (all P>0.05). LASSO-Cox sensitivity analysis verified the robustness of the findings in this study.

Dynamic change in serum complement C3, especially the persistently reduced phenotype, is independently associated with the long-term risk of renal function progression in patients with lupus nephritis. Dynamic monitoring of complement C3 level contributes to risk stratification and prognostic evaluation of lupus nephritis.

Abnormal activation of programmed cell death (PCD) plays a key regulatory role in the progression of kidney injury and fibrosis, and different modes of PCD can participate in the occurrence and development of chronic kidney disease (CKD) through diverse pathological mechanisms. Autophagy has a "double-edged sword" effect. Its moderate activation can maintain cellular homeostasis and retard renal fibrosis by clearing damaged organelles and misfolded proteins. However, its excessive activation or impaired function leads to the accumulation of harmful substances and mitochondrial dysfunction, thereby accelerating the progression of kidney diseases. Necroptosis mediates inflammatory responses and promotes renal fibrosis via the receptor-interacting protein kinases 1/3 (RIPK1/RIPK3)-mixed lineage kinase domain-like protein (MLKL) signaling pathway. Pyroptosis relies on the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, which promotes the release of pro-inflammatory factors and aggravates renal injury. Ferroptosis participates in the pathological process of CKD through lipid peroxidation and iron-dependent mechanisms. Targeted therapeutic strategies for the aforementioned PCD have exhibited potential renal-protective effects in various preclinical models, including diabetic kidney disease, unilateral ureteral obstruction, 5/6 nephrectomy, and acute kidney injury. This paper reviews the roles, mechanisms and interactions of the four PCD modalities in CKD. In the future, machine learning can be leveraged to optimize multi-target combination therapies (e.g., quercetin derivatives synergistically regulating ferroptosis and necroptosis), realize patients stratification and therapeutic effect prediction, and provide a new paradigm for precise intervention of CKD.

Immunoglobulin A (IgA) nephropathy is the most common primary glomerular disease and one of the leading causes of end-stage kidney disease. In recent years, the gut-kidney axis has become a research hotspot in the pathogenesis of IgA nephropathy. Accumulating studies have demonstrated that the onset of IgA nephropathy is closely associated with gut microbiota dysbiosis, disruption of the intestinal mucosal barrier, aberrant mucosal immune activation, and disturbed gut microbial metabolites. This review systematically summarizes the latest research progress regarding the gut-kidney axis in the pathogenesis of IgA nephropathy, and outlines novel intervention strategies based on the gut-kidney axis, including dietary modulation, gut microbiota intervention, mucosal immune regulation, and biologic agents targeting B-cells/plasma cells. Conventional therapeutic approaches that may exert benefits via modulating the gut-kidney axis are also summarized, so as to provide theoretical evidence and new research insights for individualized prevention and treatment of IgA nephropathy.

To investigate the effectiveness of generative AI-supported error-corrective case-based teaching in clinical nephrology clerkship.

Medical students rotating through the Department of Nephrology at the Army Specialized Medical Center from June 2024 to September 2025 were selected and randomly assigned to an experimental group and a control group using a random number table. The control group received traditional case-based teaching, while the experimental group underwent generative AI-supported error-corrective case-based teaching. Both groups received a 2-week clinical training period. The pre- and post-teaching examination scores, learning engagement and critical thinking level were compared between the two groups, and their comprehensive learning effect and teaching satisfaction were evaluated after teaching.

A total of 64 medical students were enrolled, with 32 in each group. Post-teaching assessment results showed that the case-analysis score [(42.50±4.56) vs (38.47±4.75)] and total examination score [(82.06±8.09) vs (75.97±7.37)] in the experimental group were higher than those in the control group (all P<0.05). The scores of dedication dimension [(30.34±5.95) vs (27.63±4.84)], absorption dimension [(34.53±7.31) vs (25.38±5.66)] and total learning-engagement score [(92.19±9.09) vs (79.19±8.10)] were higher in the experimental group (all P<0.05). The experimental group also obtained higher scores in learning effect [(67.41±4.31) vs (60.25±6.61)], learning experience [(38.09±3.21) vs (34.19±5.37)], classroom interaction [(18.41±1.88) vs (16.50±2.11)], and academic load [(10.91±1.82) vs (9.56±2.69)] (all P<0.05). The total critical-thinking score was higher in the experimental group [(266.72±16.57) vs (252.06±13.86)], together with higher scores in the sub-dimensions of truth-seeking, open-mindedness, systematicity, critical-thinking self-confidence, and inquisitiveness (all P<0.05). The total teaching-satisfaction score of the experimental group was higher than that of the control group [(83.38±3.08) vs (79.16±4.15), P<0.05].

Generative AI-supported error-corrective case-based teaching can improve medical students′ case-analysis ability, learning engagement, learning effect, and critical thinking, and enhance teaching satisfaction.