Search Results (91)

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

Background: The complement system factors’ role in the pathogenesis of autoimmunological diseases is known, but the influence of autoantibodies against complement factors’ receptors on the course of specific glomerular diseases remains unclear. Methods: We measured the levels of anti-C3aR and anti-C5aR antibodies in patients with membranous nephropathy (n = 18), primary focal and segmental glomerulosclerosis (FSGS) (n = 25), lupus nephritis (LN) (n = 17), IgA nephropathy (n = 14), mesangial proliferative (non-IgA) glomerulonephritis (n = 6), c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis (n = 40), and p (perinuclear)-ANCA vasculitis (n = 16). These conditions were compared to a healthy control group (n = 22). Then, for up to two years, we tracked the patients’ clinical progress (in terms of creatinine, total protein, and albumin levels) and compared the outcomes with their antibody levels. Results: The lupus nephritis group had higher levels of anti-C3aR and anti-C5aR antibodies than the other groups. The lupus nephritis group’s anti-C3aR antibody level showed a negative correlation with albumin and total protein at several time points of observation. Additionally, at numerous observational points, the anti-C3aR antibody level showed a positive correlation with both the basic albumin level in the FSGS group and the total protein level. Conclusions: The anti-C3aR and anti-C5aR antibodies are higher in lupus nephritis patients compared to other glomerulonephritis patients and healthy individuals. Albumin and total protein levels appear to be correlated positively with anti-C3aR antibody levels in FSGS and negatively in lupus nephritis. Full article

Background: Autoimmune diseases and other immune-mediated disorders are associated with an increased risk of malignancy, influenced by chronic inflammation, immune dysregulation, and treatment-related factors. Clarifying cancer risk patterns across specific conditions is essential to improve clinical vigilance and inform screening practices. Objective: The aim of this study was to synthesise current evidence on the association between autoimmune and immune-mediated diseases and cancer, with a focus on practical implications for clinicians. Methods: Recent cohort studies, meta-analyses, and expert consensus documents were analysed to describe cancer epidemiology, pathogenic mechanisms, high-risk phenotypes, and treatment considerations across major autoimmune diseases and other immune-mediated conditions. The review covers idiopathic inflammatory myopathies, Sjögren’s syndrome, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, ANCA-associated vasculitis, giant cell arteritis, polymyalgia rheumatica, sarcoidosis, mixed connective tissue disease, IgG4-related disease, VEXAS syndrome, and eosinophilic fasciitis. Special attention was given to identifying warning features for underlying malignancy and evaluating cancer screening strategies. Results: The magnitude and distribution of cancer risk vary across diseases. In some conditions such as dermatomyositis, systemic sclerosis or Sjögren’s syndrome, increased risk is well established, particularly for haematological and certain solid tumours. However, tumour patterns may differ across populations, and findings are not always consistent. Distinct clinical and serological features help stratify individual cancer risk and may guide the intensity of screening. The first years after disease onset often represent a window of higher vulnerability, during which intensified surveillance may be warranted in selected patients. Conclusions: Cancer risk in autoimmune diseases should be assessed on an individual basis. Awareness of disease-specific risk factors and clinical warning signs supports early recognition of malignancy and informs screening decisions in routine practice. Full article

Background: IgA vasculitis (IgAV) represents the most frequently seen form of vasculitis among children. Although it often resolves without intervention, renal involvement (IgAV nephritis) poses a risk for long-term complications. Although the lectin and alternative complement pathways are possible causes in its development, dependable serum biomarkers for the early identification of nephritis remain unavailable. Methods: In this prospective case-control study, we examined how the serum levels of a membrane attack complex (sC5b-9), complement factor H (CFH), mannose-binding lectin (MBL), and mannose-binding lectin-associated serine protease-1 (MASP-1) relate to renal involvement in IgAV. These complement proteins were measured in children diagnosed with IgAV and compared to levels in healthy controls (HCs) matched for age and sex. Results: The study cohort comprised 44 IgAV patients with a median age of 8 years and 34 HCs. The CFH levels were reduced significantly in the patient group (median: 357.31 ng/mL; IQR: 228.32) relative to the controls (median: 543.08 ng/mL; IQR: 504.05) (p < 0.001). This decrease was observed irrespective of the presence of nephritis. There were no significant differences in serum sC5b-9, MBL, or MASP-1 levels between the patients and controls. Furthermore, no correlation emerged between these complement components and renal involvement. Conclusion: The data suggest that lower CFH levels may signal systemic dysregulation of the alternative pathway in IgAV. In contrast, the serum levels of sC5b-9, MBL, and MASP-1 appear inadequate as markers for predicting renal involvement. Further research with larger cohorts that includes genetic analyses and examination of kidney tissue is needed to better define the contribution of complement activation in IgAV-related nephritis. Full article

Riedel thyroiditis (RT) is a rare immune-mediated inflammatory disease that destroys the thyroid parenchyma, replacing it with storiform fibrosis extending to the extrathyroidal tissue. Secondary fibrotic lesions can be associated as parts of the systemic IgG4-related disease. We present the case of a 52-year-old female patient who presented initially with subacute thyroiditis when corticosteroid treatment was initiated. After a year, compressive respiratory symptoms and dysphagia appear, and fine-needle aspiration cytology is performed to rule out malignancy, but without results. Thyroidectomy is performed, and histopathology shows scleroatrophic thyroiditis, with chronic inflammatory infiltrate containing eosinophils extending in the neighboring tissue, rare atrophic follicles, and obliterative vasculitis. Immunohistochemistry proves abundant plasma cells with IgG4 secretion; the macrophage is mainly the M2 subtype. RT is diagnosed, and a CT (computed tomography) scan is performed to detect peritracheal fibrosis and subtle pulmonary modifications. A literature review was performed that situates our findings in the context of the current literature. The last part discusses the immuno-inflammatory mechanisms behind IgG4-related diseases. Full article

Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article

Immunoglobulin A vasculitis (IgAV), previously known as Henoch–Schönlein purpura (HSP), is a type of non-thrombocytopenic small-vessel vasculitis. HSP is the most common systemic vasculitis in pediatric patients, and it is characterized by purpura, arthritis or arthralgia, gastrointestinal pain, and renal dysfunction. This retrospective analysis also examines a range of demographic factors, including sex, geographic and environmental influences, age, and medication, to evaluate their potential effects on the pediatric population affected by HSP. The five-year hospital-based retrospective analysis included 138 hospitalized children diagnosed with HSP during hospitalization. Blood sample analysis was conducted to assess various immunological parameters, including levels of immunoglobulins (IgA and IgE), complement components (C3 and C4), C-reactive protein, fibrinogen, the erythrocyte sedimentation rate (ESR), and allergen panels. Elevated IgE levels and normal IgA serum concentrations were found to be strongly associated with infectious diseases in pediatric HSP patients. Patients with recurrent infectious diseases consistently exhibited elevated IgE levels and normal IgA levels during treatment despite no identified allergens, alongside an increased risk of disease recurrence. Full article

Cryoglobulinemia is a rare disorder characterized by the presence of abnormal proteins (cryoglobulins) in the blood that precipitate at low temperatures. It presents with a wide clinical spectrum, from mild symptoms to severe, life-threatening disease. In mixed cryoglobulinemia (MC), vascular damage results from immune complexes—typically monoclonal IgM with rheumatoid factor activity and polyclonal IgG (Type II), or polyclonal/oligoclonal IgM and IgG (Type III). These complexes can obstruct small blood vessels, leading to ischemia and leukocytoclastic vasculitis. Renal involvement occurs in about 30% of MC patients and it is a manifestation with poor prognosis. Nowadays, types II and III MC are the most common forms, often linked to autoimmune diseases like Sjögren’s syndrome and systemic lupus erythematosus, or to viral infections such as hepatitis B or persisting despite hepatitis C eradication. This review explores renal involvement in MC, offering a comprehensive perspective on current knowledge, including recent advances in pathophysiological understanding, evolving diagnostic strategies, and novel therapeutic approaches. In this context, “perspectives” refers to the growing recognition of the shifting epidemiology of MC—particularly the changing etiological landscape following hepatitis C virus eradication—as well as the integration of emerging clinical and pathological entities such as cryofibrinogenemia and monoclonal gammopathy of renal significance into diagnostic and management frameworks. Furthermore, the review highlights current therapeutic strategies recognized as most effective, emphasizing the importance of a multidisciplinary and multimodal approach that combines etiological treatment, B-cell–targeted therapy (notably rituximab), plasma exchange in selected cases, and comprehensive supportive care for renal and systemic complications. Moreover, the landscape of management could be enriched in future years, since clinical trials are ongoing to explore novel therapies for refractory or relapsing cases of MC with renal involvement. Full article

There is rapidly increasing evidence of the role of complement in different forms of kidney disease and this has broadened the field to involve not only atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G), but also a number of other glomerular diseases, mainly ANCA-associated renal vasculitis, immune-complex glomerulonephritis, membranous nephropathy, and IgA nephropathy (IgAN). In parallel, the field of therapeutic agents able to target the three complement pathways at different levels, both proximally and terminally, has grown tremendously in recent years. This has led to the approval of agents targeting complement for ANCA-associated vasculitis, IgA nephropathy, and, very recently, C3 glomerulopathy. The real-world implementation of these agents remains a challenge. This review will attempt, through the presentation of representative clinical vignettes, to provide some practical guidance for the nephrologist in how to navigate these new therapeutic opportunities, focusing on aHUS, C3G, and IgAN. Full article

Background: Anti-PAR 1 (protease-activated receptor 1) and anti-ACE 2 (angiotensin 2-converting enzyme 2) antibodies are a kind of non-HLA (human leukocyte antigens) antibodies postulated to be of significance in autoimmunological diseases and organ transplantation. Methods: We assessed anti-PAR 1 and anti-ACE 2 antibody levels in patients with membranous nephropathy n= 18, focal and segmental glomerulosclerosis (FSGS) n = 25, lupus nephritis (LN) n = 17, IgA nephropathy n = 14, mesangial proliferative (non-IgA) glomerulonephritis n = 6, c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis n = 40, p (perinuclear)-ANCA vasculitis n = 16, and compared them with a healthy control group n = 22. Next, we observed the clinical course of the patients (creatinine, total protein, and albumin) up to 2 years and correlated the results with the level of antibodies. Results: The anti-PAR 1 antibody level was lower in membranous nephropathy and FSGS compared to the control group. Anti-PAR 1 antibody levels were higher in secondary compared to primary glomerulonephritis. Both anti-PAR 1 and anti-ACE 2 antibody levels correlated positively (in focal and segmental glomerulosclerosis) or negatively (in lupus nephritis) with total protein and albumin at different time points of observation. Anti-PAR 1 and anti-ACE 2 antibody levels correlated also with creatinine level at one time point of observation in IgA nephropathy. Anti-PAR 1 and anti-ACE 2 antibodies correlated with each other in membranous nephropathy, FSGS, and p- and c-ANCA vasculitis (p < 0.05). Conclusions: The anti-PAR 1 antibody level was lower in membranous nephropathy and focal and segmental glomerulosclerosis compared to the control group. Anti-PAR 1 antibody levels tend to be higher in secondary compared to primary glomerulonephritis. Full article

Objective: This study aimed to identify clinical and laboratory predictors of kidney involvement and disease relapse in pediatric patients with IgA vasculitis (Immunoglobulin A vasculitis, IgAV). Materials and Methods: A retrospective cohort study was conducted on 173 children diagnosed with IgAV at the Children’s Clinical Hospital of the Medical University of Warsaw between 2018 and 2022. Patients were categorized into groups based on renal involvement (IgAVN+ vs. IgAVN−) and disease recurrence. The analysis included demographic data, clinical manifestations, allergy history, presence of infection, duration of hospitalization, relapse occurrence, the interval between the first and second hospitalization, and laboratory markers. Results: Renal involvement was observed in 42% of cases, while disease recurrence occurred in 9.25% of patients. IgAVN+ patients were older, had longer hospital stays, and more frequently exhibited gastrointestinal symptoms, consistent with previous research. A history of allergic conditions was more prevalent in both the IgAVN+ and recurrence groups. An increase in IgA levels over time was associated with a higher risk of nephropathic development. Patients with recurrences had higher IgM levels and an elevated neutrophil-to-lymphocyte ratio (NLR) (p = 0.07). In the ROC (Receiver Operating Characteristic) analysis, a cutoff value of 1.67 for NLR (AUC 0.71; p = 0.0002; sensitivity 0.87; specificity 0.58) was identified as a risk factor for disease recurrence. Conclusions: Older age at disease onset, gastrointestinal involvement, and allergies are associated with renal involvement in pediatric IgAV. Immune dysregulation, reflected by elevated NLR and IgM, may contribute to disease recurrence. It is important to monitor changes in IgA levels over time, as an increase in IgA concentration is a risk factor for the development of nephropathy. Additionally, calculating the NLR is recommended, as it may indicate the probability of disease recurrence. Full article

Background/Objectives: A limited number of previous studies have reported high rates of end-stage renal disease (ESRD) in adults with IgA vasculitis nephritis (IgAVN). Despite the high prevalence of the disease and the high rates of ESRD reported in the literature, no specific guidelines for adult patients have been established and there is no consensus on the management of the disease. This study aimed to prospectively investigate adults with IgAVN from a broad perspective. Methods: This investigation was designed as a prospective observational study and was conducted between 01.02.2022 and 01.10.2024. A total of 49 newly diagnosed adult (>18 years) patients with IgAVN were regularly followed up. At the end of the study, the renal remission rates, factors influencing remission, treatment data, treatment-related adverse events, and disease outcomes were determined. Results: The median follow-up time was 22 (IQR: 11–24) months. A total of 42 patients (87%) received immunosuppressive treatment in addition to the initial glucocorticoid treatment. Azathioprine (AZA) was the preferred (41%) first steroid-sparing agent. ESRD occurred in only one patient (2%), while a total of ten patients (20%) had an unfavorable outcome. The rate of nephrotic-range proteinuria (NRP) was significantly higher in the patients who did not achieve renal remission at the end of the 12-month follow-up period (9,7% vs. 60%; p = 0.02) and NRP was an independent risk factor for unfavorable outcomes [OR: 17.18; 95% CI: 1.31–224.95; p = 0.03]. A total of 16% of the patients developed an infection that required hospitalization during follow-up; these patients had a higher rate of IgAVN-associated acute kidney injury (62.5% vs. 22%; p = 0.02) and were significantly older (mean: 46 ± 15.3 vs. 65 ± 13.3; p = 0.002). One patient died of sepsis at 4 months and another died of a myocardial infarction at 32 months. Conclusions: These results suggest that adults with IgVAN do not have a high rate of ESRD if they receive effective immunosuppressive therapy. However, immunosuppressive therapy is associated with an increased risk of infection, particularly in the elderly. The presence of NRP is associated with lower long-term remission rates and has a predictive value for unfavorable outcomes. Full article

Kidney transplantation is the most effective replacement therapy for kidney failure, providing the best outcomes in terms of patient survival and offering a better quality of life. However, despite the progressive improvement in kidney survival, the recurrence of original disease remains one of the most important causes of graft loss and a major challenge that requires clinical vigilance throughout the transplant’s duration. Additionally, the type and severity of recurrence affect both treatment options and graft survival. This is especially true for the recurrence of systemic diseases. In this narrative review, we will discuss the timing, frequency, severity, and treatment of post-transplant recurrence in three systemic diseases: lupus nephritis (LN), Antineutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (ANCA-GN), and Henoch–Schönlein purpura (HSP). The recurrence of lupus nephritis is less common than that of primary focal segmental glomerulosclerosis or C3 glomerulopathy. Its severity can range from mild mesangial to diffuse proliferative forms, with varying prognoses and treatment options, much like the original disease. In some patients with LN, as well as in those with ANCA-GN or HSP, the reactivation of the primary disease can affect other organs besides the kidneys, potentially leading to life-threatening conditions. These cases may require a multidisciplinary approach, making these transplants clinically more challenging. Extrarenal flare-ups often necessitate an increase in immunosuppression, which in turn raises the risk of infections. In these autoimmune diseases, the role of immunological tests in determining the timing of kidney transplants remains a topic of ongoing debate. However, elevated levels of certain immunological markers, such as anti-dsDNA antibodies, ANCA titers, or serum immunoglobulin A may indicate a reactivation of the disease, suggesting the need for more intensive patient monitoring. Full article

Background/Objectives: Immunoglobulin A (IgA) vasculitis (IgAV), classically known as Henoch–Schönlein purpura (HSP), is a type of nonthrombocytopenic small-vessel vasculitis. HSP is the most frequent kind of systemic vasculitis in children, characterized by purpura, arthritis or arthralgia, gastrointestinal pain, and kidney dysfunction. The aim of our research was to investigate and observe the clinical characteristics of children diagnosed with HSP and to explore the correlation between infectious diseases and HSP. Furthermore, this retrospective study considered other factors, such as demographic characteristics (sex, area/environment, and age), and their effect on the pediatric population diagnosed with HSP. Methods: To answer this question, we conducted a five-year hospital-based retrospective study that included 144 hospitalized children who were diagnosed with HSP during hospitalization. Measurements of immunological panels (IgA, IgM, IgG, and IgE), C3, C4, C-reactive protein, fibrinogen, and hematite sedimentation rate (VSH) determined using blood samples revealed that there is a strong correlation between the elements of the immunological panel and the HSP manifestations. Results: Additionally, elevated IgG and normal IgA serum levels in pediatric HSP patients are strongly associated with infectious diseases. Conclusions: Notably, patients with infectious diseases exhibited high IgG and normal IgA serum levels post-treatment and a higher risk of relapses. Full article

Background: Anti-ETAR (endothelin A receptor) antibodies and anti-CXCR3 (C-X-C motif chemokine receptor 3) antibodies are types of non-HLA (human leukocyte antigens) antibodies that could have some influence on the course of glomerulonephritis. The authors aimed to study the influence of these antibodies’ levels on the course of specific glomerulonephritis types. Methods: We evaluated the anti-ETAR and anti-CXCR3 antibody levels in the serum of patients with membranous nephropathy (n = 18), focal and segmental glomerulosclerosis (FSGS) (n = 25), systemic lupus erythematosus (n = 17), IgA nephropathy (n = 14), mesangiocapillary glomerulonephritis (n = 6), anti-neutrophil cytoplasmic antibodies (c-ANCA) vasculitis (n = 40), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) vasculitis (n = 16), and we compared their levels with the control group (n = 22). Next, we observed the patients’ clinical parameters (serum creatinine, albumin, total protein) for 2 years and checked the correlation of the clinical course markers with basic receptor antibody level. Results: Our results indicate lower anti-ETAR antibody levels in patients with FSGS and IgA nephropathy compared to the control group. Both types of antibodies correlated with creatinine levels after 2 years of observation in IgA nephropathy. Both types of antibodies seemed to negatively influence the total protein and albumin levels in systemic lupus erythematosus. Conclusions: This prospective observation showed that anti-ETAR and anti-CXCR 3 antibody levels are connected with the course of IgA nephropathy and lupus nephritis. Full article