Mesangial hypercellularity and excessive extracellular matrix (ECM) accumulation are defining lesions of mesangial proliferative glomerular diseases and drivers of progressive glomerulosclerosis and renal dysfunction. How mesangial cells (MCs) remain quiescent within the mechanically dynamic glomerular microenvironment, and why this control fails in disease, remain incompletely understood, in part because few in vitro systems combine three-dimensional architecture, heterotypic cell interactions, and defined mechanical loading. We therefore developed a simplified three-dimensional (3D) co-culture system using immortalized mouse cell lines: MCs embedded in a type I collagen gel, overlaid with a monolayer of mouse microvascular endothelial cells and subjected to orbital-shaking-induced fluid-flow-derived mechanical loading, intended to model indirect loading rather than pressure-driven interstitial perfusion. In MC monoculture, fluid flow markedly increased MC expansion and Ki-67-positive cell density, whereas an overlying endothelial monolayer substantially attenuated this proliferative response under flow and reduced cleaved caspase-3-positive (CC3) apoptotic MCs. Endothelial co-culture suppressed MC p38 MAPK and AKT phosphorylation under both static and fluid-flow conditions, while flow increased ERK phosphorylation in the endothelial layer despite reduced total ERK abundance. Fluid flow enhanced MC collagen accumulation (Picrosirius Red staining), whereas endothelial co-culture reduced total and type III collagen deposition under both conditions. These findings indicate that fluid flow and the endothelial monolayer are key determinants of the mesangial microenvironment, with flow prompting proliferation and the endothelium restraining proliferation and matrix deposition largely independently of flow. We propose that disruption of this endothelial-mesangial cross-talk may contribute to the mesangial expansion and fibrosis of mesangial proliferative glomerulonephritis.

Type I interferonopathies are a heterogeneous group of monogenic autoinflammatory disorders characterized by dysregulated type I interferon (IFN-I) signaling due to pathogenic variants that affect nucleic acid sensing, processing, or downstream signaling pathways. Mutations in genes including TREX1, RNASEH2A/B/C, SAMHD1, ADAR1, STING1 (TMEM173), PSMB8, COPA, and DNASE1L3 lead to persistent activation of innate immune pathways, particularly the cGAS-STING, MDA5, and Toll-like receptor pathways, with subsequent JAK-STAT signaling and sustained overexpression of interferon-stimulated genes. Chronic IFN-I activation promotes endothelial dysfunction, vascular inflammation, and tissue injury, providing a mechanistic link between interferonopathies and vasculitic disorders. Clinically, these conditions present with diverse manifestations, including chilblains, livedo reticularis, necrotizing cutaneous vasculopathy, panniculitis, interstitial lung disease, cerebral vasculopathy, and glomerulonephritis, often resembling autoimmune diseases such as primary central nervous system vasculitis, systemic lupus erythematosus (SLE), poliarteritis nodosa (PAN), immune complex vasculitis, and ANCA-associated vasculitis (AAV). A persistently elevated interferon gene signature represents a valuable diagnostic biomarker that distinguishes these disorders from most classical autoimmune vasculitides and facilitates early recognition. Timely genetic testing is essential to establish an accurate diagnosis, guide patient management, and avoid treatment delays. The present review summarizes the molecular mechanisms linking IFN-I dysregulation to endothelial injury and vasculitis, discusses the clinical spectrum and diagnostic challenges of monogenic interferonopathies, and highlights emerging targeted therapies, particularly Janus kinase inhibitors, that support precision medicine approaches for interferon-driven inflammatory diseases.

C3 glomerulopathy (C3G) includes dense deposit disease and C3 glomerulonephritis, both of which can be associated with membranoproliferative glomerulonephritis. The prevalence and true burden of C3G in Italy is difficult to estimate due to the rarity of the disease and a lack of epidemiological and patient-reported data. Moreover, diagnosis of C3G is challenging and complex due to its nonspecific clinical characteristics, a continually evolving disease classification, and the need for careful interpretation of immunofluorescence, light microscopy and electron microscopy kidney biopsy findings. Here, we provide a narrative review of the relevant literature, along with 38 consensus statements specific to the Italian context that were developed by an eight-member scientific advisory board, and voted on by a 42-member expert panel, with consensus reached using Delphi methodology. We outline the patient journey and management of C3G in Italy, highlighting ways of improving the current pathway, and suggesting steps to improve our understanding of the disease. The consensus statements cover: epidemiology of C3G in Italy; classification of C3G; histology and diagnostic procedures; management of patient symptoms; the patient journey in C3G in terms of diagnosis, treatment and follow-up; and disease burden and quality of life. Two rounds of voting were conducted, and consensus (at least 66.6% of panelists voting agree/strongly agree on a 4-point Likert scale) was reached for all statements. These consensus statements, while specific to the Italian context, are broadly applicable globally and provide an overview of this rare disease as well as the necessary diagnostic steps.

Congenital complete atrioventricular block (CCAVB) is a well-recognized manifestation of neonatal lupus erythematosus (NLE), caused by transplacental transfer of maternal anti-Ro/Sjögren's Syndrome Type A (SSA) and anti-La/Sjögren's Syndrome Type B (SSB) antibodies. Although non-cardiac manifestations of NLE typically resolve within the first year of life, the long-term autoimmune risk in affected offspring remains unclear. We report a 24-year-old woman with CCAVB secondary to maternal Sjögren's disease who presented with acute heart failure, nephrotic-range proteinuria, bicytopenia, pericardial effusion, and findings concerning for Libman-Sacks endocarditis. Despite negative conventional lupus serologies, renal biopsy demonstrated Class IV/V lupus-like immune-complex glomerulonephritis with full-house immune complex deposition, leading the multidisciplinary team to favor seronegative lupus nephritis. This case demonstrates the diagnostic limitations of serology-based approaches in atypical lupus presentations and underscores the critical role of tissue biopsy. The case also raises questions regarding long-term autoimmune risk after autoimmune congenital heart block, an area for which prospective data and evidence-based surveillance strategies remain limited.

Renal disease in people living with HIV extends beyond classical HIV-associated nephropathy to include immune-mediated and vasculitic lesions, of which pauci-immune crescentic glomerulonephritis is among the rarest and most easily missed. We describe two biopsy-proven cases with anti-myeloperoxidase anti-neutrophil cytoplasmic antibody positivity. The first, established on antiretroviral therapy, presented with a pulmonary-renal syndrome after empirical anti-tubercular treatment had failed; biopsy showed cellular crescents without chronic change, and corticosteroids with rituximab achieved sustained clinical, biochemical and serological remission. The second, antiretroviral-naive, had glomerular haematuria and proteinuria documented at HIV diagnosis and an ischaemic stroke soon afterwards, but declined nephrological assessment; biopsy 3 years later was dominated by global glomerulosclerosis and interstitial fibrosis and he remained dialysis-dependent. The divergence turned on the histological stage at diagnosis rather than antiretroviral status and argues for early biopsy whenever unexplained renal decline with an active urinary sediment occurs in HIV.

Anti-glomerular basement membrane (GBM) antibody disease is an autoimmune-mediated rapidly progressive renal injury. The coexistence of diffuse non-hereditary glomerular basement membrane thinning of uncertain etiology in elderly patients is clinically rare and poses substantial challenges in differential diagnosis and clinical management. We herein report a 70-year-old female patient admitted for elevated serum creatinine for more than 20 days. After a prodromal infection, she rapidly progressed to anuria and acute kidney injury (AKI), with markedly elevated serum anti-GBM antibody levels. Renal biopsy revealed crescentic glomerulonephritis, and electron microscopy demonstrated diffuse thinning of the glomerular basement membrane; genetic testing excluded hereditary thin basement membrane nephropathy. The patient received methylprednisolone pulse therapy, cyclophosphamide immunosuppression, plasma exchange, and maintenance hemodialysis. Long-term dynamic monitoring of antibody levels and imaging indicators was performed after discharge. During hospitalization and follow-up, anti-GBM antibody levels declined continuously, subsequent infection was gradually controlled by antimicrobial therapy, and the patient remained hemodialysis-dependent with stable overall condition. Renal biopsy combined with genetic testing is the core method to distinguish lesions of diffuse non-hereditary glomerular basement membrane thinning of uncertain etiology, from hereditary basement membrane lesions. This case represents an elderly patient with oligoimmune atypical anti-GBM antibody disease and diffuse non-hereditary glomerular basement membrane thinning of uncertain etiology, and this long-term follow-up record provides valuable clinicopathological reference for individualized treatment and prognostic evaluation of similar rare cases.

ANCA-associated vasculitis (AAV) presents with rapidly progressive glomerulonephritis, yet the tissue-level molecular landscape in pediatric AAV remains poorly understood. We aimed to characterize spatially resolved renal disease programs across different histopathological stages of pediatric AAV and compared with adult AAV.

Dietary risks are key modifiable contributors to chronic kidney disease (CKD) worldwide; however, their association with geographic or socioeconomic status remains underexplored. We aimed to quantify the global, regional, and national burden of CKD attributable to dietary risks from 1990 to 2021 using estimates from the Global Burden of Disease Study (GBD) 2021. Estimates of disability-adjusted life-years (DALYs) of CKD attributable to dietary risks were stratified by age, sex, location, and Socio-demographic Index (SDI) across 204 countries and territories from 1990 to 2021. We performed a comprehensive risk assessment for 7 dietary factors of CKD stratified by underlying causes: CKD due to type 2 diabetes mellitus (T2DM), hypertension, glomerulonephritis, and other unspecified causes. Every DALY estimate was accompanied by a 95% uncertainty interval. In 2021, the global age-standardized DALY rates of CKD attributable to dietary risks were 93.52 (95% uncertainty interval, 54.29-134.38) per 1,00,000. The leading dietary contributors were low fruit (38.68 [20.15-57.77] per 1,00,000) and vegetable (30.84 [14.80-50.20]) intake and high sodium (19.81 [2.51-54.57]) intake. The DALY rates increased sharply with age, with higher rates among males, reaching 920.46 in males and 840.16 in females at ages 95 years or above for low fruit intake. Low SDI regions showed a higher burden from CKD due to hypertension, attributable to fruit (54.23) and vegetable (55.99) deficiencies, while high SDI regions exhibited a greater burden from CKD due to T2DM, attributable to highly processed meat (11.36) and a relatively high burden from red meat (6.59) and sugar-sweetened beverages (4.01), with the greatest increase from high sugar-sweetened beverage intake (121.08%). The global burden of CKD attributable to dietary risk remains substantial, with persistent disparities in age, sex, location, and SDI. Targeted dietary strategies are needed to address these disparities and reduce the CKD burden worldwide.