Search Results (464)

Kidney diseases in patients with SLE include glomerulonephritis (GN), tubulointerstitial nephritis (TIN) and vasculitis alone or in combination. Immune complex (IC) deposition with complement activation in renal glomeruli causes lupus GN. However, IC deposition can also occur in the tubular basement membrane, renal interstitium, peritubular capillaries and arteries/arterioles to elicit inflammatory responses. TIN is usually associated with more severe GN with inflammation induced by IC. Immunopathologically, the aberrant presentation of T cell subpopulations, T_h1, T_h2, T_h9, T_h17, Treg and follicular T helper cells (T_fh), is closely implicated in TIN in SLE. In addition, M₁/M₂ macrophages and more specific dendritic cells (DCs) contribute to the inflammatory reactions of SLE-TIN. TIN may also present alone (isolated TIN) in apparently normal glomeruli or class I GN. It is intriguing that lupus nephritis constitutes two different pathological predilections, i.e., GN and tubulointerstitial inflammation. Alternatively, these two types may represent a continuous spectrum of inflammatory renal damages. In the present review, we will discuss in detail the pathology/immunopathogenesis, likely specific biomarkers/predictors and novel therapeutic designs for SLE-tubulointerstitial inflammation. In addition, we also raise several plausible investigation methods in SLE-tubulointerstitial inflammation that may help further elucidate this setting of perplexing renal diseases with rheumatic characteristics. Full article

Background and Aims: C1q is an autoantigen in different autoimmune disorders, Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN) among them. The two functional domains of C1q, the collagen-like region (CLR) and the globular head region (gC1q), are frequently recognized by autoantibodies in SLE and LN when C1q is immobilized. We studied whether autoantibodies to C1q in SLE and LN patients recognized C1q as a soluble autoantigen and whether the act of immobilization was a prerequisite for the recognition of C1q autoepitopes localized on gC1q domains. Methods: The interaction of soluble C1q and its globular fragments ghA, ghB, and ghC with immobilized IgG autoantibodies (and vice versa) from sera of 48 patients with SLE and LN was studied with ELISA. Data were compared using Spearman correlation coefficient. Fluorescence spectroscopy was used to study the interaction between C1q and LN IgG autoantibodies both presented in solution. Results: We found that anti-C1q autoantibodies from SLE and LN patients specifically bound C1q and gC1q fragments, ghA, ghB, and ghC, both as immobilized and soluble antigens. Correlation analysis indicated a negative correlation between the levels of autoantibodies against immobilized and soluble C1q and immobilized and soluble gC1q fragments which indicates different epitopes when these proteins were recognized as autoantigens in soluble and immobilized conformations. Conclusions: Serum C1q in patients with SLE is a target molecule for binding from anti-C1q autoantibodies. The gC1q region undergoes a conformational change in an immobilized and a soluble form, thus exposing different epitope-binding sites. Full article

Studies examining IgG subclasses within circulating immune complexes (CICs) in patients with IgG4-related disease remain scarce. A Japanese man in his 50s with a history of diabetes mellitus and chronic pancreatitis was referred to our department because of an increase in serum creatinine levels. Serum IgG and IgG4 levels were markedly high, accompanied by eosinophilia and elevated serum IgE levels. C3 hypocomplementemia and an increase in CICs were also noted, and imaging revealed swollen mediastinal lymph nodes. Renal biopsy revealed extensive tubulointerstitial nephritis with numerous IgG4-positive plasma cells and dense interstitial fibrosis. The patient was diagnosed with IgG4-related disease, and glucocorticoid therapy was initiated; renal function, serological abnormalities, and swelling of the mediastinal lymph nodes improved. Subsequent analyses revealed that the patient’s CICs mainly comprised IgG4 and that there was tubular deposition of complement components C1q, C4d, C3, and C5b-9 in the renal biopsy tissue, suggesting that immune complexes containing IgG4 activated the complement pathway in circulation and locally in the kidneys. Hypocomplementemia and CICs are observed in a subset of patients with IgG4-related diseases; however, the underlying mechanisms remain unclear. Further accumulation of IgG4-related disease cases is required to evaluate the possibility of IgG4-mediated complement activation. Full article

Background: Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), necessitates effective therapeutic strategies. Polysaccharides derived from Irpex lacteus have demonstrated beneficial biological activities in MRL/lpr mice; however, their precise mechanisms of intervention in LN require further elucidation. Methods: MRL/lpr mice were administered low-dose and high-dose Irpex lacteus polysaccharide (PCP) continuously for 8 weeks. The therapeutic efficacy of PCP was systematically assessed by measuring autoantibody levels, inflammatory cytokine expression, and renal function markers. The underlying pharmacological mechanisms were investigated through integrated transcriptomics and metabolomics analyses. Results: PCP treatment significantly improved renal function in MRL/lpr mice, normalizing serum levels of anti-nuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-Sm antibody (Sm), creatinine (Cr), blood urea nitrogen (BUN), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and proteinuria. Integrated transcriptomic and metabolomic analyses revealed that the therapeutic action of PCP involves modulation of the PI3K/AKT/NF-κB pathway. This inhibition was further confirmed by Western blot analysis. Conclusions: PCP exerts renal protective effects in MRL/lpr mice by mitigating inflammation, modulating immune responses, and preserving renal function. The combined application of transcriptomics, metabolomics, and Western blotting elucidates that this protection is mediated through inhibition of the PI3K/AKT/NF-κB signaling pathway. Full article

Objective: To determine infectious complications and explore potential prognostic factors associated with mortality in patients with lupus nephritis (LN) admitted to the intensive care unit (ICU). Methods: We conducted a retrospective analytical study of 20 patients with biopsy-proven LN admitted to a tertiary ICU between 2022 and 2023. Clinical, histopathological, microbiological, and paraclinical data were collected. Associations with mortality were explored using Firth’s penalized logistic regression. Results: The mean age was 37 ± 14 years; 85% were female. Hypertension (50%) was the most frequent comorbidity. Mean ICU stay was 13 ± 27 days; in-hospital mortality was 15%, and 60% required hospital readmission. Sepsis was the leading reason for ICU admission (55%), predominantly respiratory and gastrointestinal. In the exploratory analysis, respiratory tract infection (OR 1.43; 95% CI: 1.19–9.90; p = 0.04), proliferative LN (OR 2.12; 95% CI: 1.32–17.34; p = 0.03), and hypocomplementemia (C3) (OR 1.72; 95% CI: 1.25–10.40; p = 0.02) showed point estimates suggestive of higher odds of mortality. Conclusions: In this cohort of critically ill patients with LN, respiratory tract infection, proliferative histological class, and hypocomplementemia were associated with higher mortality. These findings require validation in larger prospective studies to determine their utility in risk stratification and ICU management. Full article

Patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) are at increased risk of severe infections, making effective vaccination strategies essential. While antibody responses to SARS-CoV-2 vaccination have been studied in SLE, less is known about innate immune correlates. Therefore, we evaluated cytokines with a particular emphasis on interferon and chemokine profiles. To fulfill the immunological picture, we also assessed neutralizing antibodies against SARS-CoV-2 variants, lymphocyte subpopulations, and selected gene expression signatures in 33 patients stratified by vaccination status: fully vaccinated (FV, n = 23) and partially vaccinated (PV, n = 10). Serum analyses showed that FV patients exhibited increased type I (IFN-α2, IFN-β) and type III (IFN-λ1, IFN-λ2/3) interferons, as well as elevated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-12p70) and IL-10, whereas neutralizing antibody (Neut. Ab.) titers against wild-type and variant strains, including Omicron, were comparable between groups. Immunophenotyping demonstrated preserved T- and B-cell subset distributions, except for reduced CD8⁺CD197⁺CD45RA⁻ (central memory) T cells in FV patients. ISG15 gene expression was upregulated in the T cells of FV patients. Correlation analyses linked IL-6 with disease activity and IL-8, GM-CSF, IFN-β, IL-10, and Alpha Neut. Ab. with organ damage. Complement C3 correlated inversely with IFN-α2 and IFN-γ, while C4 correlated positively with Alpha and Omicron Neut. Ab. These findings highlight that vaccination in SLE induces distinct interferon and cytokine signatures without consistent enhancement of neutralizing antibodies against SARS-CoV-2, underscoring the importance of integrated immune correlates in assessing vaccine responses in this population. Full article

Background/Objectives: Henoch–Schönlein purpura (HSP), or IgA vasculitis, is the most common small-vessel vasculitis in children, yet Indian cohort data remain limited. We aimed to describe the clinical profile, renal involvement, treatment patterns, relapse, and outcomes of pediatric HSP at a tertiary centre in South India. Methods: We conducted a retrospective review of children <18 years diagnosed with HSP (January 2013–October 2018) using EULAR/PRINTO/PRES criteria. Demographics, clinical features, laboratory parameters, treatments, and outcomes were abstracted from records and analyzed in SPSS (descriptive statistics; Chi-square/Fisher’s exact and t/non-parametric tests as appropriate). Subgroup comparisons included renal vs. non-renal disease and age <6 vs. ≥6 years. An exploratory analysis examined predictors of nephritis. Results: Of 43 children identified, 2 were excluded (misclassified as systemic lupus erythematosus); 41 were analyzed. Mean age was 8.5 years (range 3–17), male: female 1.4:1. A preceding febrile illness or upper respiratory tract infection was noted in 41.4% and 17%, respectively. Palpable purpura was universal; joint involvement 73.1%, abdominal pain 61.0%, vomiting 41.5%. Renal involvement 17% occurred only in children ≥6 years; exploratory testing supported a strong age-linked signal for nephritis. Laboratory abnormalities included anemia (48.7%), thrombocytosis (19.5%), and elevated ESR (51.2%). Skin biopsy (n = 29) showed IgA and complement deposition; renal biopsy (n = 2) showed ISKDC grades II–III. Treatments included NSAIDs 71.6%, corticosteroids 31.7%, and dapsone 24.4% (used for severe systemic/persistent cutaneous disease). Rash relapse 7.3% clustered with joint plus abdominal symptoms and was not observed among children with nephritis. At a mean 18.9-month follow-up, one child required long-term antihypertensives; no child progressed to end-stage renal disease. Conclusions: Pediatric HSP in this South-Indian cohort followed a largely self-limited course with favourable renal outcomes. Age ≥6 years flagged higher renal risk, supporting age-targeted urine and blood-pressure surveillance, while relapse appeared to follow a non-renal trajectory (joint/abdominal clustering). Steroid and dapsone use reflected clinical severity rather than relapse risk. Findings align with Indian series and suggest lower renal morbidity than some East-Asian reports, adding region-specific evidence to guide monitoring and counselling. Full article

Copper is an essential trace element that supports numerous physiological functions; however, excessive copper accumulation can disrupt cellular and biological processes. In this study, forty-eight male mice were randomly divided into four groups (n = 12): Control (fed normal rice), Cu300 (300 mg/kg copper), Cu300+Se (Cu300 + selenium-enriched rice), and Cu300+iSe (Cu300 + 1 mg/kg iSe), and were treated for 180 days. Copper exposure resulted in reduced body weight, hepatomegaly and nephritis, elevated copper deposition in organs, oxidative stress, and significant declines in RBC, HGB, and WBC counts, leading to anemia and immunosuppression. Selenium supplementation, effectively mitigated these effects by reducing copper accumulation, restoring antioxidant balance, and enhancing selenoprotein-related functions. Histopathological analysis revealed that copper toxicity induced hydropic degeneration and focal necrosis in hepatic and renal tissues, effects that were significantly attenuated by selenium supplementation. Transcriptomic profiling revealed that selenium-enriched rice reversed copper-induced gene expression changes. In the liver, selenium treatment significantly upregulated protective genes such as Slc7a, Bola1, Uqcrq, Dtx1, and Znrd2, while downregulating stress-related genes like Trim75, Dpm3, Moxd1, Tnfrsf25, and Gpr75. In the kidneys, selenium enhanced the expression of detoxification and immune-modulating genes (Mt1, Mt2, Rhbdl1, Crisp3, Mif) and suppressed stress-related genes (Nnt, Ifi44l, NLRP12, Eno1b, Ugt1a), demonstrating its role in mitigating oxidative and inflammatory stress. Collectively, these findings demonstrate that selenium-enriched rice exerts potent protective effects against chronic copper toxicity through multiple mechanisms: (1) restoration of mitochondrial function, (2) attenuation of ER stress and apoptosis, (3) enhancement of antioxidant and detoxification pathways, and (4) modulation of metabolic and immune responses. This study highlights selenium-enriched rice as a promising nutritional intervention for mitigating chronic copper toxicity and maintaining hepatorenal health. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease frequently complicated by hematologic abnormalities, which may reflect disease activity or treatment effects. To characterize the clinical, laboratory, and immunological features of adult SLE patients referred to hematology during routine rheumatology follow-up. Methods: We retrospectively analyzed 84 adult SLE patients who fulfilled the 2012 SLICC or 2019 EULAR/ACR criteria and were referred to hematology during follow-up. Clinical, laboratory, and immunological data were collected. Associations between hematologic manifestations, organ involvement, autoantibodies, and complement levels were evaluated. Results: The cohort included 92.6% females with a median age of 46 (IQR 36–62). Hematologic abnormalities commonly appeared within three years of disease onset. Lymphadenopathy was more frequent in patients with cutaneous vasculitis and lupus nephritis (p = 0.046 and p = 0.045). Splenomegaly was associated with serositis, anti-β2 glycoprotein I IgG, and lupus anticoagulant (LA) positivity; anti-β2GPI IgG independently predicted splenomegaly (OR 26.02, p = 0.006). Low C4 was associated with increased autoimmune hemolytic anemia risk (OR 5.88, p = 0.009), while low C3 was linked to lupus nephritis (p = 0.017). Antiphospholipid antibodies were significantly associated with venous thrombosis, with anti-cardiolipin IgG as an independent predictor (OR 7.43, p = 0.007). Stroke history, anti-histone antibodies, and higher steroid doses were associated with mortality. Remission was linked to fewer comorbidities (p = 0.008). Conclusions: Hematologic complications in SLE arise early and carry prognostic significance, with splenomegaly associated with lupus anticoagulant and anti-β2GPI IgG, and mortality linked to anti-histone antibodies. Full article

Chronic kidney disease (CKD) affects as many as 10% of the population, which translates to about 850 million globally. Even though genetics, diabetes, and hypertension contribute to CKD, the underlying pathologic processes remain poorly understood. Mast cells (MCs) are unique tissue immune cells capable of secreting numerous biologically active molecules. MCs have been associated with kidney diseases and poor CKD outcomes, but they have received limited attention in CKD research. MCs are typically located perivascularly and are identified through kidney biopsies, which limits their diagnostic utility. MC-specific biomarkers such as histamine and the proteases chymase and tryptase show potential, but signature biomarker profiles are needed. While MC biomarkers have been studied in non-renal diseases, their clinical relevance in kidney disease remains underexplored. This review aims to clarify the role of MCs in kidney diseases, such as diabetic nephropathy, IgA nephropathy, hypertensive nephropathy, pruritus, parathyroidism, renal amyloidosis, and lupus nephritis, as well as in conditions such as kidney fibrosis, inflammation, and kidney transplant rejection. Evidence indicates an increased number of MCs, as judged by increased urine levels of histamine, chymase, IL-33, metalloproteinase-9 (MMP-9), and tryptase. In conclusion, MCs are involved in the pathogenesis of CKD and may represent new targets for early diagnosis, prevention, and treatment. Full article

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which environmental factors modulate genetically determined immune dysregulation. Vitamin D has emerged as a plausible modifier of disease expression because its active metabolite signals through the vitamin D receptor on innate and adaptive immune cells and influences antigen presentation, cytokine balance, and lymphocyte differentiation. This narrative review synthesizes current evidence on vitamin D status and supplementation in SLE with attention to organ-specific domains. Observational studies consistently report high rates of hypovitaminosis D in SLE and associations with less favorable clinical profiles, including higher global and renal disease activity, adverse cardiometabolic features, greater infection vulnerability, and neuropsychiatric manifestations. Preclinical models demonstrate neuroprotective and barrier-stabilizing actions of vitamin D analogs, supporting biological plausibility. Interventional trials indicate that supplementation safely corrects deficiency and shows signals of benefit for selected outcomes (e.g., modest activity reductions or fatigue in specific contexts), although effects on interferon signatures, complement, and autoantibodies are heterogeneous and often limited. Overall, current evidence supports optimization of vitamin D status as a low-risk adjunct in comprehensive SLE care while highlighting the need for adequately powered, organ-focused randomized trials using standardized measurements and prespecified endpoints to define causality, therapeutic targets, and long-term safety. Full article

Non-diabetic chronic kidney disease (ND-CKD) refers to the progressive and irreversible decline in kidney function occurring in the absence of diabetes mellitus—a distinction that sets it apart from the more prevalent diabetic CKD. While diabetic nephropathy remains the leading cause of CKD globally, ND-CKD encompasses a heterogeneous group of etiologies, including hypertensive nephrosclerosis, glomerulonephritis, and interstitial nephritis. Its incidence and prevalence are steadily increasing, particularly in aging populations, and are often underrecognized. Importantly, ND-CKD is not a benign entity; it independently contributes to systemic inflammation, oxidative stress, and metabolic dysregulation, which in turn amplify cardiovascular risk. Among the most severe complications is heart failure (HF), a complex syndrome arising from structural and functional impairments in cardiac performance. Despite ongoing advancements in HF management, mortality remains unacceptably high, ranging from 2–3% at 30 days to up to 50–75% over five years. Standard pharmacologic therapies frequently fall short in halting disease progression and may provoke undesirable side effects. This therapeutic gap has spurred growing interest in natural compounds with multi-targeted effects. Bioactive molecules such as arjunolic acid, kaempferol, luteolin, and resveratrol have shown anti-inflammatory and antioxidant properties that may offer dual benefits for both renal and cardiac function. By modulating shared molecular pathways—including those involved in inflammation, oxidative damage, and cellular dysfunction—these agents hold promise as adjunctive treatments in ND-CKD complicated by heart failure. Full article

Reliable clinical markers for predicting sustained renal remission remain poorly understood in patients with lupus nephritis (LN). We investigated whether achieving complete renal remission (CRR) within 6 months of induction therapy, compared to within 12 months, was associated with a higher likelihood of attaining CRR at 24 months. We conducted a retrospective observational study of biopsy-proven patients with class III or IV ± V LN treated at a lupus clinic in Australia. CRR was defined as a urine protein: creatinine ratio (UPCR) of <0.05 g/mmol with no worsening of eGFR > 10% from baseline. CRR responders at 6, 12, and 24 months were determined. Associations between 6- and 12-month CRR status and 24-month CRR were examined using logistic regression. In total, 60 patients were included; 49 (82%) were female, with a median age of 27 years (IQR: 19, 39) at LN diagnosis. CRR was attained at 6, 12, and 24 months by 23 (40%), 26 (47%), and 24 (44%) of patients, respectively. Both 6- and 12-month CRR attainment were significantly associated with an increased likelihood of CRR achievement at 24 months (adjusted odds ratios 11.23 (95% CI 2.53, 49.88) and 11.39 (95% CI 2.41, 53.80), respectively). Achieving CRR at 6 and 12 months was a strong independent predictor for attaining subsequent renal remission. Full article

Background and Objectives: Lupus nephritis (LN) is a major cause of mortality and morbidity in patients with systemic lupus erythematosus (SLE). Biomarkers derived from blood, urine, and multi-omics techniques are essential for enabling access to less invasive methods for LN evaluation and personalized precision medicine. Materials and Methods: The purpose of this work was to review the studies that addressed the potential role of urinary and serological biomarkers for the diagnosis, disease activity, response to treatment, and renal outcome of adult patients with LN, published over the past decade, and summarize their results with a particular emphasis being directed towards the available traditional tools. Results: Traditional biomarkers used for the diagnosis and surveillance of LN are proteinuria, urinary sediment, estimated glomerular filtration rate (eGFR), anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-C1q, and serum complement levels. Anti-dsDNA, serum C3, and proteinuria are the conventional biomarkers with the strongest clinical evidence, with overall moderate ability in predicting LN from non-renal SLE, disease activity, renal flares, response to therapy, and prognosis. The last decade has brought significant progress in our understanding regarding the pathogenesis of LN and, consequently, several molecules, either alone or in combination panels, have emerged as potential novel biomarkers, some of them outperforming conventional biomarkers. Promising results have been suggested for urinary activated leukocyte cell adhesion molecule (ALCAM), soluble cluster of differentiation 163 (CD163), C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein 1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and vascular cell adhesion molecule 1 (VCAM-1). Conclusions: Despite the intensive research of the last decade, no novel biomarker has entered clinical practice, and we continue to rely on traditional biomarkers to assess non-invasively LN and guide its treatment. Novel biomarkers should be validated in multiple longitudinal independent cohorts, compared with conventional biomarkers, and integrated with renal histology information in order to optimize the management of LN patients. Full article

Recurrence of the original glomerular disease (GN) poses a significant threat to kidney transplant function and longevity. The probability and severity of this recurrence vary, with C3 glomerulopathy and certain forms of FSGS exhibiting particularly high rates. Kidney transplant GN recurrence risk hinges on the characteristics of the initial GN, recipient/donor genetics, recipient age, donor type, end-stage kidney disease (ESRD) progression rate, and proteinuria levels. Standard immunosuppression has limited efficacy in preventing primary disease recurrence; however, agent selection and induction therapy can influence the risk for specific GNs. Diagnosing recurrent GN involves a comprehensive approach, including clinical evaluation, laboratory tests (such as proteinuria, hematuria, and specific biomarkers like anti-PLA2R for membranous nephropathy or complement for C3G), and, critically, an allograft biopsy analyzed with light, immunofluorescence, and electron microscopy. Treatment strategies are evolving towards targeted therapies, such as rituximab for antibody-mediated GN and complement inhibitors for C3G, moving away from broad immunosuppression. This narrative literature review provides practical monitoring algorithms for post-transplant settings, synthesizing information on the incidence, predictors, diagnostic strategies, and therapeutic options for various glomerular disease subtypes. The methodology involved searching MEDLINE, Embase, and Cochrane databases from 1996 to 2025, prioritizing systematic reviews, cohort studies, registries, and interventional reports. Eligibility criteria included adult transplant recipients and English-language reports on recurrent glomerular disease outcomes, excluding most single-patient case reports. Limitations include potential selection bias, omission of relevant studies, and the absence of a formal risk-of-bias assessment or meta-analysis. The evidence base is heterogeneous, with inconsistent outcome reporting and scarce randomized controlled trials. Future efforts should focus on developing predictive biomarkers, standardizing diagnostic and response criteria, conducting multicenter prospective cohorts and pragmatic trials, and creating shared registries with harmonized data. Full article