抗糸球体基底膜腎炎

BACKGROUND: The study aimed to evaluate the efficacy and safety of eculizumab in addition to conventional therapy for anti-glomerular basement membrane (anti-GBM) disease presenting rapidly progressive glomerulonephritis (RPGN). METHODS: 42 patients with anti-GBM disease presenting with RPGN were included in this multicenter retrospective cohort study. All patients received intensive immunosuppressive therapy including intravenous methylprednisolone pulses followed by maintenance prednisone, in combination with at least two of the following: intravenous cyclophosphamide, therapeutic plasma apheresis, rituximab, or eculizumab. The cohort was stratified into two groups: the eculizumab group (n = 13) which received eculizumab (900 mg once weekly for 1-5 doses) in combination with other therapies, and the control group (n = 29) which did not receive eculizumab. Kidney survival at 12 weeks and 24 weeks, and adverse events (infections, metabolic alterations, laboratory abnormalities), ascertained via clinical and laboratory data. RESULTS: At 12 weeks, the eculizumab group showed significantly higher kidney survival compared with the control group (69.2% vs. 31.0%, p = 0.021). At 24 weeks, kidney survival remained numerically higher in the eculizumab group (66.7% vs. 40.7%, p = 0.081). Kaplan-Meier curves for renal survival by the Gehan-Breslow-Wilcoxon test, which places greater emphasis on early events, revealed a statistically significant difference between the groups (χ² = 4.137; p = 0.042); however, the difference assessed by the log-rank test did not reach statistical significance (χ² = 3.491; p = 0.062). There were no significant differences in the overall incidence of infections or other adverse events. CONCLUSION: Combined therapy with eculizumab showed improved early kidney survival for anti-GBM nephritis at 12 weeks, and did not increase the risk of adverse events. Prospective, large-sample studies with long-term follow-up are needed to validate its efficacy and safety.

The incidence of diabetes mellitus (DM) is increasing worldwide, especially for its major renal complications, diabetic nephropathy (DN) and chronic kidney disease (CKD). These are caused by chronic hyperglycemia, oxidative stress, hemodynamics, inflammation, and profibrotic signaling, which result in progressive renal structural damage and functional decline. All these mechanisms contribute to podocyte injury, thickening of the glomerular basement membrane, interstitial fibrosis, and progressive loss of renal function. While traditional diagnostic markers like albuminuria or estimated glomerular filtration rate (eGFR) aid in tracking disease with imaging, and emerging markers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin C can help, none can detect early, subclinical kidney damage. A comprehensive literature review was conducted in PubMed, Google Scholar, Scopus, Web of Science, and ScienceDirect using keywords related to DN pathophysiology, diagnosis, nanomedicine, renal targeting, and nanoformulations, with publications between 2015 and 2026. Intensive glycemic and blood pressure control, inhibition of the renin-angiotensin-aldosterone system, and lipid-lowering therapy are currently used as therapeutic interventions. Poor bioavailability, off-target toxicity, complex dosing regimens, and variable renal drug handling are often responsible for their limited effectiveness. One approach to circumventing these limitations is with nanotechnology-based drug delivery systems. In preclinical studies, the antioxidant, anti-inflammatory, and antifibrotic effects have consistently been reported to be superior, with reduced systemic toxicity, while clinical translation remains in its early stages. This review discusses current knowledge on DN and critically evaluates the pros, cons, and future of nanotechnology-based approaches for delivering targeted nanomedicines to the kidney.

Hypoxia-inducible factor 1α (HIF-1α) promotes T helper 17 (Th17) differentiation, but whether it regulates ADAM9 expression in Th17 cells during autoimmune nephritis remains unclear. Hypoxia enhanced Th17 differentiation and increased ADAM9 expression in a HIF-1α-dependent manner. HIF-1α deficiency reduced ADAM9 expression and impaired Th17 differentiation in vitro. In anti-glomerular basement membrane nephritis and B6.lpr lupus-prone mice, T cell-specific HIF-1α deletion attenuated renal pathology and reduced kidney-infiltrating CD4+ and IL-17A-producing T cells. These findings identify ADAM9 as a HIF-1α-regulated target in Th17 cells that may contribute to autoimmune renal inflammation.

Nintedanib (NIB), a small-molecule tyrosine kinase inhibitor (TKI), is approved for idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease. Although nephrotoxicity is uncommon, cases of nephrotic syndrome (NS), acute kidney injury (AKI) and glomerular lesions including thrombotic microangiopathy (TMA) and anti-glomerular basement membrane (GBM) nephritis have been reported. However, the optimal management of NIB-associated glomerular disease remains undefined. We report a 69-year-old man with IPF, hypertension, diabetes and underlying chronic kidney disease who developed persistent NS and renal dysfunction 16 months after initiation of NIB. Kidney biopsy demonstrated glomerular endothelial injury with microangiopathic features, accompanied by secondary collapsing focal segmental glomerulosclerosis (FSGS) and background diabetic kidney disease. Despite discontinuation of NIB and intensification of renin-angiotensin system inhibition and mineralocorticoid receptor blockade, nephrotic-range proteinuria persisted. Subsequent initiation of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was temporally associated with a gradual and sustained reduction in proteinuria, with partial remission achieved while preserving the estimated glomerular filtration rate. To our knowledge, this is the first report of NIB-associated glomerular endothelial injury with secondary collapsing FSGS in which SGLT2i initiation was temporally associated with sustained proteinuria reduction under concomitant supportive therapy. TKIs may induce both endothelial and podocyte injury and therapeutic options beyond drug withdrawal remain limited. In this context, SGLT2 inhibition may represent a potential adjunctive therapeutic strategy in selected cases with underlying chronic kidney disease and warrants further systematic evaluation.