Tribulus terrestris L. extract alleviates diabetic nephropathy through regulation of oxidative stress and inflammation: insights from in silico, in vivo and LC-MS/MS-based metabolite profiling studies.

HMGCS2 desuccinylation modulates acetoacetate to drive tubule-macrophage inflammatory crosstalk in diabetic kidney disease.

A 16S rRNA-based meta-analysis of gut microbiota in diabetic nephropathy using QIIME2 and publicly available NGS datasets.

Shenxiao decoction ameliorates podocyte injury in diabetic nephropathy via upregulating RUNX3 expression and inhibiting the JAK2/STAT3 signaling pathway.

Suoquan Yishen formula attenuates ectopic lipid deposition in diabetic kidney disease by inhibiting UBC9-mediated SUMO1 modification of DRP1.

Jujuboside A ameliorates glomerular podocytes lipotoxicity in diabetic mice by YY1-mediated promotion of intracellular cholesterol transport and efflux.

The role of complement protein and complement regulatory protein in diabetic nephropathy.

Non-steroidal mineralocorticoid receptor antagonist finerenone ameliorates diabetic nephropathy via suppressing SLC7A11-mediated ferroptosis.

Dual versus monotherapy with SGLT2 inhibitor and GLP-1 receptor agonist: PRECIDENTD pragmatic randomized trial.

The urine albumin-to-creatinine ratio (uACR) level is an essential biomarker for the early screening and monitoring of chronic kidney disease (CKD), particularly among patients with diabetic and hypertension. However, uACR requires quantitative assay, where the use of designated analyzers makes the assays difficult for large-scale screening. In this study, we developed a decentralized, instrument-free microfluidic microspheres accumulation platform (MMAP) that visualizes the uACR in patients with diabetic nephropathy. Albumin inhibits the binding between magnetic microspheres (MMSs) and polymer microspheres (PMSs) due to competitive immunoassay interactions, while creatinine is recognized by the anti-creatinine aptamer, which releases a DNA blocker strand to facilitate connections between MMSs and PMSs through DNA hybridization. The binding of MMSs and PMSs prevents PMSs from escaping magnetic attraction in the inlet, thereby reducing the free PMS accumulation length in the measurement zone of the microfluidic chip. The PMS accumulation length allows for the visual quantification of uACR with excellent selectivity, tolerance to varying pH levels, and high accuracy comparable to that of standard tests in the hospital. As a convenient, low-cost assessment tool that correctly classified all clinical samples in this pilot cohort to evaluate CKD stages from normal to end-stage, this device offers significant benefits for disease self-monitoring and community health services.

In FIDELITY, finerenone improved kidney and cardiovascular (CV) outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines categorise CKD progression risk based on estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). This FIDELITY post hoc subanalysis investigated KDIGO risk category changes associated with finerenone. Improvement or worsening in KDIGO risk category was defined by variation from baseline, with specified eGFR and UACR changes. Association of these category changes with a CV composite outcome was assessed. Finerenone therapy led to a higher likelihood of KDIGO risk category improvement (odds ratio [OR], month 36: 1.47; 95% confidence interval [CI], 1.31-1.65; p<0.0001) and lower likelihood of worsening (OR, month 36: 0.83; 95% CI, 0.77-0.90; p<0.0001) vs. placebo. Risk category improvement reduced the CV composite outcome risk (hazard ratio [HR]: 0.82; 95% CI, 0.68-0.99; p=0.043) while worsening increased this risk (HR: 1.29; 95% CI, 1.06-1.56; p=0.01). Finerenone therapy is associated with greater improvement and less worsening in KDIGO risk vs. placebo. The category changes are associated with lower risk of CV events in patients with CKD and T2D. FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) are registered with ClinicalTrials.gov (funded by Bayer AG).

Herpetic ocular infections in solid organ transplantation: A narrative review.

Impact of diabetic foot ulcers and nephropathy on risk of treatment-warranted diabetic eye disease: A retrospective cohort study

Endothelial Ffar4 protects against diabetic kidney disease by potentiating endogenous retinoic acid metabolism.

The implementation gap between evidence-based SGLT2 inhibitor therapy and real-world practice remains substantial in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Protocolized care delivery bundles incorporating frequent follow-up, systematic monitoring and adherence support may bridge this implementation gap. To evaluate the impact of a a structured, nurse-delivered multi component pathway (frequent contact, protocolized monitoring, and adherence reminders) on kidney function progression and clinical outcomes in patients with T2DM and CKD. This single-center, retrospective cohort study included 450 patients with T2DM and CKD who initiated SGLT2 inhibitors between February 2024 and February 2025. Patients were categorized into structured nurse-delivered multi component pathway management (n = 225) or conventional care (n = 225) groups. Primary outcomes included annualized eGFR decline rate and composite kidney endpoint (≥ 40% eGFR decline, end-stage kidney disease, or kidney-related death). Propensity score weighting was applied to balance baseline characteristics. The structured nurse-delivered multi component group demonstrated a slower annualized eGFR decline compared to conventional care. The composite kidney endpoint occurred less frequently in the structured nurse-delivered multi component group (HR 0.68, 95% CI 0.52-0.89, P = 0.004). Laboratory follow-up compliance was significantly higher in the structured nurse group (82.3% vs. 64.7%, P < 0.001). Adverse event-related drug discontinuation was lower with structured nurse-delivered multi component group (8.4% vs. 15.2%, P = 0.012). A structured SGLT2 inhibitor management bundle delivered through a nurse-coordinated pathway reflecting greater care intensity and standardized follow-up was associated with improved kidney function trajectories and fewer adverse kidney outcomes in routine practice. The clinical trial was registered in the Chinese Clinical Trial Registry (ChiNHSMU20231015).

Diabetic nephropathy (DN) is a major complication of type 1 diabetes (T1D). Current diagnostic parameters, such as albuminuria and estimated glomerular filtration rate (eGFR), often detect the disease at advanced stages, promoting the identification of additional inflammatory markers. This study investigated the potential roles of pro-inflammatory interleukin-26 (IL-26), anti-inflammatory interleukin-35 (IL-35), and Signal Transducer and Activator of Transcription 1 (stat1) gene expression as potential biomarkers of DN in T1D. To evaluate serum levels of IL-26 and IL-35 and the gene expression of stat1 in T1D patients with and without renal dysfunction to assess their involvement in DN. This case-control study included 80 T1D patients (subgrouped to nephropathy status) and 60 healthy controls. Serum cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA), and stat1 expression in the blood was assessed using quantitative real-time PCR (qPCR). Statistical analyses included ANOVA, correlation tests, and receiver operating characteristic (ROC) curve analysis. IL-26 levels were not significantly elevated in hemodialysis T1D patients. IL-35 levels were significantly higher in T1D patients with nephropathy and in those on hemodialysis. A significant positive correlation was observed between IL-26 and IL-35 levels (r = 0.561, p = 0.0002). stat1 gene expression was significantly elevated in all T1D subgroups compared to controls, with the highest level observed in the hemodialysis group. ROC analysis indicated that stat1 had a discriminative ability for T1D, whereas IL-35 showed an acceptable diagnostic value for end-stage renal disease. This study showed that stat1 expression and IL-35 levels were linked with renal impairment in the T1D context, with stat1 expression elevated across T1D subgroups, and IL-35 expression was more accentuated in advanced renal dysfunction. Despite its limited discriminative value, IL-26 correlates with IL-35, suggesting simultaneous regulation within the inflammatory microenvironment.

Diabetic nephropathy (DN), a leading cause of end-stage kidney disease (ESKD), often progresses despite standard care. Evidence suggests a DN subgroup exhibit overlapping features of primary podocytopathy, potentially responsive to immunosuppression, has not yet systematically studied. We hypothesized that DN patients with biopsy-proven concurrent ultrastructural features of primary podocytopathy will demonstrate superior renal outcomes following immunosuppressive therapy, compared to those with isolated DN pathology. A retrospective analysis was conducted on 88 patients with biopsy-confirmed DN recruited from Peking University First Hospital between 2017 and 2022. The patients were categorized into two groups: Group A (patients with DN and primary podocytopathy) and Group B (patients with DN without primary podocytopathy). Seven patients with diabetes and primary podocytopathy but without DN served as disease controls. Primary podocytopathy was defined by electron microscopy foot process width (FPW) ≥821nm. Patients in Group A had a shorter duration of nephropathy (p=0.005), lower serum albumin levels (p<0.001), and higher proteinuria (p=0.032) than those in Group B. Light microscopy demonstrated milder glomerular lesions in Group A (p<0.001), with most cases classified as Class I or II (63.6%). Electron microscopy showed significantly broader FPW in Group A than in Group B (1310.5±510.1nm vs. 569.1±97.5nm, p<0.001). While Group B showed no such benefit and differed significantly from the control group, patients in Group A benefited from immunosuppressive therapy, with a significantly reduced risk of ESKD. DN with concurrent primary podocytopathy represents a distinct clinical entity characterized by nephrotic-range proteinuria, ultrastructural podocyte effacement, and favorable response to immunosuppressive therapy. Early renal biopsy incorporating FPW assessment enables targeted therapy to mitigate ESKD progression in this high-risk phenotype.

Podocyte injury is a hallmark of diabetic nephropathy (DN) and significantly contributes to disease progression. Accumulating evidence suggests that impaired autophagy exacerbates podocyte dysfunction under hyperglycaemic conditions. However, the underlying regulatory mechanisms remain incompletely understood. This study aimed to investigate the role and mechanism of microRNA-10a-5p (miR-10a-5p) in regulating podocyte injury and autophagy in DN. The function of miR-10a-5p was explored in high glucose (HG)-induced murine podocyte (MPC5) cells and streptozotocin (STZ)-induced diabetic mice. Gain- and loss-of-function experiments were conducted using miR-10a-5p mimics or inhibitors. E2F transcription factor 7 (E2f7) was predicted as a downstream target of miR-10a-5p via bioinformatics, and the binding between miR-10a-5p and E2f7 was assessed using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Podocyte injury, cell apoptosis, inflammation and autophagy were assessed using flow cytometry, Western blotting, enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining. Rescue experiments were conducted by silencing or overexpressing E2f7 to confirm its role in miR-10a-5p-mediated effects. miR-10a-5p was significantly upregulated in HG-stimulated podocytes and kidney tissues of diabetic mice. Inhibition of miR-10a-5p alleviated HG-induced podocyte injury, as evidenced by enhanced cell viability, reduced apoptosis and inflammatory cytokine production, and restored autophagic activity. E2f7 was identified as a direct target of miR-10a-5p. Notably, silencing E2f7 abrogated the protective effects of miR-10a-5p inhibition on podocyte survival and autophagy, and E2f7 overexpression restored the detrimental effects of miR-10a-5p overexpression on podocytes. Invivo, administration of AntagomiR-10a-5p in STZ-induced diabetic mice ameliorated renal injury and restored autophagic flux, and increased E2f7 expression in mouse renal tissues. This study identifies the miR-10a-5p/E2f7 axis as a critical regulator of podocyte injury and autophagy in DN. Therapeutic inhibition of miR-10a-5p may represent a promising strategy for preserving podocyte function and attenuating DN injury.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiovascular and renal protection in type 2 diabetes and chronic kidney disease (CKD). Although both excess and restricted sodium intake are linked to adverse outcomes, the interaction of sodium intake with SGLT2 inhibitors has not been explored. This study aimed to examine how dietary sodium intake affects cardiorenal outcomes and whether canagliflozin modifies these effects. A post hoc analysis of the CREDENCE trial (median follow-up 2.6 years) was conducted in individuals with type 2 diabetes and CKD randomised to canagliflozin 100 mg or placebo. Using a validated formula, we estimated daily sodium intake from urine in 2573 participants, divided into low-normal sodium (LNS; n=1286) and high sodium (HS; n=1287) groups. Outcomes included the following: cardiovascular death or hospitalisation for heart failure; heart failure alone; a composite renal outcome; and all-cause death. Cox models were adjusted for confounders. Sodium intake was additionally analysed as a continuous variable to assess non-linearity. In the placebo group, LNS intake increased the risk of heart failure/cardiovascular death vs HS (adjusted HR [adjHR] 1.56 [95% CI 1.10, 2.23]). Canagliflozin significantly reduced this risk in the LNS group (adjHR 0.48 [95% CI 0.33, 0.70]) but not in the HS group (adjHR 1.05 [95% CI 0.73, 1.53]). Similar patterns were seen for heart failure alone. Sodium intake had no effect on renal outcomes, while canagliflozin reduced renal risk in both the LNS group and the HS group. Neither sodium intake nor canagliflozin influenced all-cause mortality. Continuous modelling revealed a near-linear rise in heart failure/cardiovascular death risk as sodium intake decreased in placebo recipients, while this gradient was flattened with canagliflozin. In individuals with type 2 diabetes and CKD, LNS intake increases the risk of heart failure and cardiovascular death, while renal outcomes are unaffected by sodium intake. Canagliflozin mitigates the increased cardiovascular risk in individuals with LNS intake, while offering renal protection irrespective of dietary sodium. Clinicaltrial.gov NCT02065791.

The ubiquitin-proteasome system (UPS) is important for podocyte health, but the specific UPS proteins involved in podocyte injury of diabetic nephropathy (DN) are not well known. Patients with DN have lower expression of USP46 in podocytes, which is linked to higher proteinuria. Deleting the Usp46 gene in podocytes of mice (Usp46PKO mice) led to spontaneous albuminuria and worsened podocyte injury and glomerular lesions under diabetic conditions. Mechanically, loss of USP46 caused cytosolic translocation and aggregation of TAR DNA binding protein 43 (TDP-43) in podocytes. Here, we identified acarbose as an agonist of USP46. Treatment with acarbose reduced TDP-43 aggregation in podocytes, prevented podocyte loss, and mitigated albuminuria in diabetic mice; the therapeutic efficacy of acarbose was abolished in Usp46PKO mice. This research elucidates the role of USP46 in podocyte homeostasis and injury in DN and indicates a potential therapeutic impact for acarbose in DN beyond the regulation of blood glucose concentrations through its activation of USP46.