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Objective: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease, with chronic inflammation driving its progression. This study aimed to identify immune-related diagnostic biomarkers for DKD and explore their association with immune cell infiltration.
Methods: Three glomerular transcriptomic datasets (53 DKD, 36 controls) were analyzed via batch-corrected differential expression analysis to screen immune-related differentially expressed genes (DEGs). Machine learning algorithms (least absolute shrinkage and selection operator, support vector machine - recursive feature elimination) prioritized biomarkers, validated by RT-PCR in db/db mice. Immune infiltration was assessed via CIBERSORT and EPIC.
Results: Thirteen immune DEGs were identified, enriched in cytokine signaling and leukocyte chemotaxis. Three biomarkers (albumin (ALB), AP - 1 transcription factor subunit (FOS), and S100 calcium binding protein A9) showed strong correlations with T cell, natural killer cell, and macrophage infiltration, validated by RT-PCR ( < 0.001). Protein-protein interactionnetwork analysis identified ALB and FOS as hub genes (ROC Area Under the Curve: 0.803, 0.795), linking immune dysregulation to glomerular injury.
Conclusion: ALB and FOS serve as novel immunogenetic biomarkers for DKD, highlighting chronic inflammation as a key driver. This framework supports precision immunomodulation, though clinical validation in larger cohorts is needed.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247103 | PMC |
http://dx.doi.org/10.1080/0886022X.2025.2525467 | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
Clin J Am Soc Nephrol
September 2025
University College London Great Ormond Street Hospital for Children and Institute of Child Health, London, UK.
Background: Experience with icodextrin use in children on long-term peritoneal dialysis is limited. We describe international icodextrin prescription practices and their impact on clinical outcomes: ultrafiltration, blood pressure control, residual kidney function (RKF), technique and patient survival.
Methods: We included patients under 21 years enrolled in the International Pediatric Peritoneal Dialysis Network (IPPN) between 2007 and 2024, on automated PD with a daytime dwell.
Clin J Am Soc Nephrol
September 2025
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland USA.
Socioeconomic, environmental and lifestyle factors shape kidney health. Among the social determinants of health, access to healthy foods is particularly significant. As a basic need, food is integral to an individual's identity, culture, and health.
View Article and Find Full Text PDFClin J Am Soc Nephrol
September 2025
Kidney Division, Peking University First Hospital, Peking University Institute of Nephrology; Key Laboratory of Kidney Disease, Ministry of Health of China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China.
Background: The Therapeutic Effects of Steroids in IgA Nephropathy Global (TESTING) trial demonstrated that glucocorticoid therapy reduced proteinuria and improved kidney outcomes in patients with Immunoglobulin A Nephropathy (IgAN). Galactose-deficient IgA1 (Gd-IgA1) plays a central role in IgAN pathogenesis by promoting immune complex formation. However, the effects of glucocorticoid on pathogenic IgA levels remain unclear.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Department of Medicine, Institute for Transformative Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
The β-adrenergic receptor (βAR), a prototype G protein-coupled receptor, controls cardiopulmonary function underpinning O delivery. Abundance of the βAR is canonically regulated by G protein-coupled receptor kinases and β-arrestins, but neither controls constitutive receptor levels, which are dependent on ambient O. Basal βAR expression is instead regulated by the prolyl hydroxylase/pVHL-E3 ubiquitin ligase system, explaining O responsivity.
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