Emerging evidence suggests that mucosal immune responses in the tonsils may be associated with clinical features of immunoglobulin A nephropathy (IgAN). This study characterised the tonsillar microbiota implicated in IgAN using 16S ribosomal RNA gene sequencing. We retrospectively analysed tonsillar tissues from 20 patients with biopsy-proven IgAN and 19 patients with recurrent tonsillitis (RT) who underwent tonsillectomy. The microbiota composition was determined via 16S rRNA sequencing, and the disease-associated genera were identified using the Boruta feature selection algorithm. Their associations with clinical outcomes after tonsillectomy were evaluated using receiver operating characteristic curve analysis, Kaplan–Meier analysis, and log-rank tests. A total of 194 and 190 genera were detected for IgAN and RT. The α-diversity did not differ significantly between the groups, but the β-diversity analysis revealed distinct microbial community structures (p < 0.01). Boruta identified Actinomyces, Parvimonas, Streptococcus, Catonella, Bacillus, and Pseudomonas as key discriminating genera. Pseudomonas and Bacillus were enriched in the IgAN group. The area under the curve for the prediction of complete remission at 3 years based on Pseudomonas abundance was 0.712. The complete remission and proteinuria remission rates were significantly higher for the patients with Pseudomonas (p = 0.03 for both). This study reveals distinct tonsillar microbiota profiles between patients with IgAN and those with RT and shows that tonsillar Pseudomonas enrichment was associated with favourable outcomes after tonsillectomy. These findings suggest that tonsillar Pseudomonas may be associated with clinical remission after tonsillectomy in IgAN.
Tolvaptan is used to treat autosomal dominant polycystic kidney disease (ADPKD) through vasopressin V2 receptor blockade. We investigated whether the urine-to-serum (U/S) uric acid (UA) ratio, a simple, clinically accessible index, reflects early physiological changes after tolvaptan initiation and is associated with subsequent changes in renal function. This single-center prospective observational study included 72 patients with ADPKD who initiated tolvaptan. Multivariable regression analyses evaluated factors associated with the initial change in the U/S UA ratio and its association with subsequent annual changes in estimated glomerular filtration rate (eGFR). The mean observation period was 2.6 ± 1.4 years. At 1 month, serum UA increased from 6.0 ± 1.4 to 6.3 ± 1.5 mg/dL, whereas the U/S UA ratio decreased from 4.3 ± 3.1 to 1.8 ± 1.2 (both P < 0.0001). Fractional excretion of UA did not change significantly, whereas urine osmolality decreased markedly. A larger initial decrease in the U/S UA ratio was associated with a slower subsequent annual eGFR decline. However, this association was attenuated and was no longer statistically significant after adjustment for the initial change in urine osmolality. In sex-stratified analyses, the association was significant in women but not in men, although the sex-by-U/S UA ratio change interaction was not significant (P = 0.883). The U/S UA ratio is a simple, clinically accessible index reflecting early physiological changes after tolvaptan initiation. Its association with subsequent eGFR decline appears partly influenced by changes in urine osmolality and requires prospective validation.
Acute kidney injury (AKI), particularly ischemia-reperfusion injury (IRI), lacks effective targeted therapies. Protein S-palmitoylation is a reversible lipid modification involved in cellular stress responses, but its role in AKI remains unclear. We aimed to identify palmitoylation-related genes in AKI and explore their potential functions. Public transcriptome datasets of AKI kidney tissues were analyzed to identify differentially expressed genes (DEGs). Palmitoylation-related common hub genes were screened by integrating DEG analysis and weighted gene co-expression network analysis (WGCNA). Single-nucleus RNA sequencing (snRNA-seq) data and online clinical databases were used to determine cellular localization and clinical relevance. ENPP6 was further validated in a mouse renal IRI model and hypoxia/reoxygenation (H/R)-treated renal tubule cells. Six candidate common hub genes were identified: EDN1, VMP1, ENPP6, MYC, CXCR4, and EFNA1. Among them, ENPP6 was enriched in renal tubular cells and showed the strongest association with indices of renal function. ENPP6 expression was significantly reduced in the renal tubules of IRI mice at both the mRNA and protein levels. In renal tubule cells, ENPP6 overexpression was accompanied by increased overall protein S-palmitoylation. Functionally, ENPP6 overexpression improved cell viability and alleviated H/R-induced injury. ENPP6 expression was reduced in renal IRI and was positively associated with renal function. In renal tubular cells, ENPP6 overexpression was accompanied by increased global protein S-palmitoylation and reduced H/R-induced injury. These findings identify ENPP6 as a potential protective factor and a candidate for further mechanistic investigation in ischemic AKI.
Prolonged waiting for deceased-donor kidney transplantation may lead to progressive physical deterioration, particularly in countries with limited organ availability. However, the clinical significance of longitudinal changes in body composition remains unclear. This study investigated longitudinal changes in body composition and their association with subsequent adverse clinical events. This retrospective longitudinal study included 87 candidates who underwent annual bioelectrical impedance analysis in 2023, 2024, and 2025. Changes in body composition were evaluated, and multivariable logistic regression assessed associations with adverse clinical events during the subsequent 1-year follow-up. During follow-up, 24 patients experienced adverse clinical events. Between 2023 and 2025, skeletal muscle index (SMI), fat-free mass index (FFMI), and phase angle decreased, whereas extracellular water-to-total body water ratio increased (all P < 0.05). Patients who experienced adverse clinical events showed greater declines in FFMI (median change, − 0.75 vs. −0.10 kg/m²; P = 0.003) and SMI (− 0.35 vs. −0.10 kg/m²; P = 0.013). After adjustment for age, diabetes mellitus, dialysis vintage, and baseline FFMI, a greater decline in FFMI remained independently associated with adverse clinical events (odds ratio, 0.44; 95
Quadruple maintenance immunosuppression with everolimus (EVR), low-dose tacrolimus (TAC), mycophenolate mofetil, and methylprednisolone may improve allograft survival by reducing calcineurin inhibitor exposure; however, real-world long-term data on delayed EVR introduction remain limited. We retrospectively analyzed 186 adult primary kidney transplant recipients who received this quadruple regimen with EVR introduced 3–6 months post-transplantation in 2013–2023. Outcomes included graft and patient survival, post-transplant complications, and EVR-related adverse events (AEs). The association between the initial EVR dose adjusted for body surface area (BSA) and AEs was evaluated. In a secondary landmark analysis from 1 year, outcomes were compared with contemporaneous recipients on triple therapy using overlap weighting. Death-censored graft survival was 99.5
