FXR-targeted drug discovery: Recent advances and therapeutic perspectives.

BackgroundDiabetic kidney disease (DKD) is a major complication of diabetes and the leading cause of end-stage renal disease globally. Artificial intelligence (AI) technologies have shown increasing potential in DKD research for early detection, risk prediction, and disease management. However, the landscape of AI applications in this field remains incompletely mapped, especially in terms of collaboration networks, thematic evolution, and clinical translation.ObjectiveThis study aims to perform a comprehensive bibliometric and translational analysis of AI-related DKD research published between 2006 and 2024, identifying publication trends, research hotspots, key contributors, collaboration patterns, and the extent of clinical validation and explainability.MethodsA systematic search of the Web of Science Core Collection was conducted to identify English-language original articles applying AI technologies to DKD. Articles were screened following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Bibliometric visualization was performed using CiteSpace and VOSviewer to assess coauthorship, institutional and country collaboration, keyword evolution, and citation bursts. A qualitative review was conducted to evaluate clinical validation, model explainability, and real-world implementation.ResultsOut of 1158 retrieved records, 384 studies met the inclusion criteria. Global publications on AI in DKD increased rapidly after 2019. China led in publication volume, followed by the United States, India, and Iran. Keyword analysis showed a thematic transition from early biomarker and proteomic research to deep learning, clinical prediction models, and management tools. Despite methodological advances, few studies included external validation or explainability frameworks. Notable translational efforts included DeepMind’s acute kidney injury predictor and a chronic kidney disease prediction model developed by Sumit, yet widespread real-world integration remains limited.ConclusionsAI research in DKD has grown substantially over the past 2 decades, with expanding international collaboration and diversification of research themes. However, challenges persist in clinical applicability, model transparency, and global inclusivity. Future research should prioritize explainable AI, multicenter validation, and integration into clinical workflows to support effective translation of AI innovations into DKD care.

Angiopoietin-like protein 8 mediates inflammation and fibrosis of tubular cells in diabetic kidney disease progression by interacting with Akt2.

Swietenine attenuates renal tubular injury by activating mitophagy in diabetic nephropathy.

Disease management, outcomes, and healthcare resource utilization in real-life clinical practice of diabetes and diabetic kidney disease in Finland.

Identification of biomarkers to predict renal function decline and its deceleration in patients with type 2 diabetes and diabetic kidney disease.

Diabetic Kidney Disease (DKD) is a major cause of End-Stage Renal Disease (ESRD) and lacks effective treatments. Tangmaikang Granules (TMK), a multi-herb traditional Chinese medicine formulation, have shown potential in managing DKD. However, the precise active components, molecular mechanisms, and therapeutic advantages of TMK remain unclear. This study tests the hypothesis that TMK granules exert protective effects on DKD by targeting multiple pathways involved in oxidative stress, inflammation, and apoptosis in podocytes through a multi-targeted approach. The aim was to identify TMK's bioactive components, evaluate its therapeutic potential, and uncover its molecular mechanisms in DKD. The bioactive constituents in TMK were determined through ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Drug targets were identified using SwissTargetPrediction and SuperPred, whereas DKD-associated targets were obtained from the GeneCards, DisGeNET, OMIM, and TTD databases. A Protein-Protein Interaction (PPI) network was constructed, and key targets were identified via topological analysis. Molecular docking and dynamics simulations were performed to evaluate stable binding interactions. GO and KEGG pathway enrichment analyses were conducted to uncover relevant signaling pathways. TMK's effects on oxidative stress, inflammation, and apoptosis in podocytes were assessed using CCK-8, flow cytometry, RT-qPCR, ELISA, and Western blot assays. Thirty active compounds and 384 potential therapeutic targets were identified, with eight key targets. Pathway enrichment analysis revealed TMK's involvement in AGE-RAGE, EGFR, HIF-1, and apoptosis pathways, affecting inflammatory cytokine responses and oxidative stress. In vitro experiments demonstrated that TMK significantly reduced oxidative stress, inflammation, and apoptosis in podocytes by inhibiting the MAPK and NF-κB pathways. TMK granules target DKD through a multi-component, multi-target strategy, effectively mitigating oxidative stress and suppressing inflammatory and apoptotic pathways. This study integrates advanced computational and experimental methods, demonstrating TMK's unique therapeutic potential and providing a robust foundation for its clinical application in DKD management.

METTL3-mediated m6A modification of SIRT1 mRNA modulates podocyte autophagy in diabetes nephropathy with the treatment effect of Astragalus polysaccharide.

Mechanism exploration of QingReXiaoZheng Decoction on renoprotection in diabetic kidney disease: Integrated network pharmacology, molecular docking and experimental validation.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide, disproportionately affecting underserved and safety-net populations. Los Angeles County Department of Health Services (LAC-DHS) Kidney Health Workgroup has developed pragmatic population health frameworks and Expected Practices for DKD co-management with primary-care providers: pragmatic definitions of low kidney function (LKF, <50% of normal) and very low kidney function (VLKF, <25%), and proteinuria severity classification as early (>150 mg/g), heavy (>1 g/g), and massive (>7 g/g) to guide referral urgency; biopsy-agnostic diagnosis of DKD when four out of five criteria are met, including diabetes history or A1c more than 6%, LKF, proteinuria, diabetic microangiopathy, and larger kidney length (>12 cm) or faster CKD progression (>25 ml/min/year); Kidney Disease Integrated Therapy (KDIT) combining four medication categories (RAAS blockade, SGLT2 inhibitors, GLP-1 agonists, nonsteroidal mineralocorticoid antagonist) and renal nutrition and lifestyle medicine (PLADO/PLAFOND diets), adequate hydration, and exercise; and eConsults to support timely detection, dialysis vascular access placement, shared decision-making, and ESRD care coordination. The DKD management model demonstrates that resource-limited systems can deliver innovative, high-quality kidney care and provide a scalable framework for equity-focused and pragmatic kidney care in municipal health systems.

CSB6B attenuates renal inflammation and fibrosis by inhibiting the activation of NLRP3 inflammasome through the NLRP3/Caspase-1/GSDMD/IL-1β signaling pathway.

Soluble Tumor Necrosis Factor Receptors (sTNFRs) as biomarkers for Diabetic Kidney Disease.

Mechanistic insights into myricetin-regulated autophagy via the PI3K/Akt and PINK1/Parkin pathway in diabetic kidney disease treatment.

The Emerging role of lipoprotein(a) in diabetic kidney disease: possible pathophysiological links and unresolved mechanisms.

CD38 knockout attenuates type 2 diabetic renal injury by downregulating p53 and Bax via the ERK/JNK signaling pathway.

The role of oral alpha-lipoic acid as an adjuvant antioxidant therapy in diabetic nephropathy among children and adolescents with type 1 diabetes: a randomized controlled trial.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve outcomes in diabetic nephropathy (DN) and cardiovascular disease. To elucidate the underlying protective mechanisms, we explored the hypothesis that the lectin complement pathway, specifically through collectin kidney 1 (CL-K1), plays a critical role in early DN. We assessed: 1) CL-K1 abundance in the kidneys of diabetic mice, 2) the impact of SGLT-2 inhibition on CL-K1 and complement activation, and 3) the effect of CL-K1 deficiency on albuminuria and epithelial injury. Streptozotocin (STZ) was used to induce diabetes in male wild-type (WT) and CL-K1 knockout (KO) mice in three substudies. The studies evaluated time-dependent effects (14 days and 35 days), the effect of dapagliflozin, and the effect of COLEC11 gene deletion. Urine, plasma, and organ samples were analyzed for CL-K1 mRNA and protein levels by quantitative polymerase chain reaction (qPCR), Western blotting, and in situ hybridization. STZ-treated mice displayed elevated plasma glucose, increased kidney weight, urinary excretion of albumin, and kidney injury molecule-1. Kidney and plasma CL-K1 protein levels increased significantly and progressively in STZ-treated mice, whereas hepatic CL-K1 remained unchanged. Plasma mannose-binding lectin-C (MBL-C) and mannose-binding lectin (MBL)-associated serine proteases (MASP-1), as well as kidney CL-K1 and MBL-C mRNAs increased following STZ. Dapagliflozin reduced fasting blood glucose (P < 0.01), kidney (P < 0.05), and hepatic (P < 0.05) CL-K1 protein abundance, and plasma MBL-C levels (P < 0.01), without affecting mRNA levels. CL-K1 KO STZ mice exhibited a transient significant reduction in the albumin-creatinine ratio after 2 wk compared with WT STZ (P < 0.0001). Dapagliflozin reduced diabetes-related lectin pathway molecule levels in liver and kidney, potentially protecting the kidney through inhibition of this pathway.NEW & NOTEWORTHY This study investigated how SGLT-2 inhibitors (SGLT-2is) could improve kidney outcomes in early stages of diabetic nephropathy (DN) by examining changes in and contribution of collectins. We found that levels of collectin [CL-K1 and mannose-binding lectin (MBL)] increase in the kidneys of diabetic mice as injury progresses, and SGLT-2is reduce these levels. Notably, CL-K1 deletion offered temporary protection against filtration barrier injury. These findings suggest that collectins are involved in the early stages of DN, and SGLT-2is might protect the kidneys by influencing collectin activity and reducing inflammation.

HPGDS promotes tubular injury and interstitial inflammation in diabetic nephropathy by activating canonical pyroptosis pathway.

Serum analysis of type 2 diabetes mellitus patients with low, moderate, and high risk of diabetic kidney disease using LC-MS metabolomics approach.

Diagnostic and therapeutic potential of PCSK9 in diabetic tubulopathy: Evidence from observational and experimental studies.