Goodpasture's Syndrome Research Articles

#675 Application of ANCA-associated vasculitis Histopathological Classification and Renal Risk Score for prediction of end-stage kidney disease

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease predominantly characterized by inflammation of small-sized blood vessels along with the presence of circulating ANCA. The kidney is frequently involved and, even though immunosuppressive therapy has dramatically improved the outcome of AAV patients, a significant proportion of patients progress to end-stage kidney disease (ESKD). Therefore, establishing and validating tools to predict renal outcomes in patients with AAV is crucial. Here we analyzed the application of two tools in predicting kidney survival in a Portuguese single-center cohort with AAV. Method We conducted a retrospective cohort study at a tertiary-care hospital in Portugal (Hospital de São João, Porto), from December 2010 to June 2023. Patients with a kidney biopsy-proven AAV were included. Serological ANCA-negative patients and patients with overlap syndromes, such as AAV in combination with anti-glomerular basement membrane disease, were excluded. Based on electronic records, information on demographics and clinical variables were collected. Kidney biopsies were reviewed to calculate: Berden histopathological classification and the Brix Renal Risk Score (RRS). Kidney survival was defined as the time from diagnosis to the need for kidney replacement therapy. A Kaplan-Meier analysis was performed to compare kidney survival based on the mentioned classifications. Results Fifty-one patients were enrolled, 78% (n = 40) of whom were positive for myeloperoxidase (MPO). The majority were men (61%, n = 31) with a mean age of 65 (± 12) years and a mean serum creatinine of 4.59 mg/dL (± 2.74) at diagnosis. During a median follow-up of 39 (IQR, 7-84) months, 20 patients (39%) progressed to end-stage kidney disease (ESKD), 10 patients (20%) died with preserved renal function and 21 patients (41%) did not need hemodialysis. Concerning Berden classification, 13 patients with a crescentic class, 4 patients with a mixed class and 3 patients with a sclerotic class developed ESKD. After 48 months of follow-up, renal survival was 100%, 90%, 61% and 26.7% in the focal, mixed, crescentic and sclerotic class groups, respectively. Berden classification did not correlate with kidney survival (p = 0.211). Concerning RRS, 10 patients in the high-risk group and 5 patients in the medium-risk group developed ESKD. After 48 months of follow-up, renal survival was 100% in the low-risk group, 85.7% in the medium-risk group, and 41.6% in the high-risk group. A correlation was established between kidney survival and RRS score (p = 0.003). Conclusion In our cohort RRS was predictive of ESKD, contrary to Berden histopathological classification. The information derived from these risk models strongly add to standard biochemical and clinical data. Patients with higher risk of ESKD need close follow-up and a tailored treatment plan regarding preparation for renal replacement therapy.

#1155 Outcomes after kidney transplantation in anti-glomerular basement membrane disease

Abstract Background and Aims Anti-glomerular basement membrane antibody disease-associated glomerulonephritis (anti-GBM-GN) can lead to end-stage kidney disease (ESKD), requiring replacement therapy with dialysis or kidney transplant (KT). Few studies evaluated the outcome of these patients after KT. Our aim was to describe, in comparison with a control group, the occurrence of the following events: delayed graft function recovery, graft survival, relapse, acute rejection, overall survival; and to study the risk factors associated with these events. Method This was a retrospective, multicenter (6 French centers), observational study including patients who received a KT between 2005 and 2023 for ESKD secondary to anti-GBM-GN. Each vasculitis case receiving a KT was matched with 2 controls, matched on gender, center, recipient age (±5 years) and transplant period (±1 year). Event-free survival and the associated risk factors were analyzed. Results 126 patients were included, including 42 with anti-GBM-GN and 84 control patients. The median post-KT follow-up for vasculitis patients was 95 months. There was no difference in the occurrence of DGF between the groups (24 vs 18%, p = 0.5). There was no difference in graft survival when comparing both groups (78% vs 82% at 10 years, p = 0.48) (Fig. 1A). Only one patient experienced a relapse after KT (being anti-GBM negative at the time of transplantation). There was no difference in the incidence of acute rejection between the groups (p = 0.82). There was no difference in overall survival when comparing both groups (83% vs 89% at 10 years, p = 0.76) (Fig. 1B). Conclusion Kidney transplantation is an interesting option for patients with anti-GBM-GN: outcomes are similar to those of a matched population with similar occurrence of acute rejection, graft loss or death. Moreover, relapse rate is low. Comparison with a matched anti-GBM-GN population remaining on dialysis would be of interest to go further.

#1290 Adverse proinflammatory responses in the kidney after FGF23 administration in three murine kidney disease models

Abstract Background and Aims The hormone FGF23 is a biomarker associated with morbidity and mortality in individuals with and without kidney disease, but the role of FGF23 excess as a pathogenic factor is incompletely understood. Here, we investigated renal FGF23 signaling in kidney disease models. Method This study used three independent disease models: i) Male C57BL/6 mice (n = 16) were treated with Freud's adjuvant and nephrotoxic serum (NTS) to induce anti-glomerular basement membrane (anti-GBM) disease. ii) Female BALB/c mice (n = 8) were treated with adriamycin (doxorubicin) 10.5 mg/kg to induce focal and segmental glomerulosclerosis (FSGS). iii) Male DBA/2J mice (n = 20) were fed a diet containing adenine 0.2%. Control mice of the respective same strain and sex received vehicle injections. Mice of the anti-GBM and FSGS models and controls received intravenous injections of recombinant FGF23 1 µg or vehicle for six consecutive days (anti-GBM) or once (FSGS), with dissection 24 h after the last injection. Mice of the adenine model were dissected after 15 weeks. Following dissection, ex vivo precision-cut kidney slices (PCKS) were obtained from n = 4 mice and maintained for 24 at 37°C, 95% O2 and 5% CO2, followed by a 1 h treatment with recombinant FGF23 200 ng/ml or vehicle. Glomerular filtration rate (GFR) or renal retention parameters in serum and albuminuria were assessed. Kidneys underwent histological assessment using hematoxylin & eosin or Masson's trichrome. Renal RNA was isolated for bulk RNAseq. Differential gene expression was assessed to determine the effect of FGF23 treatment in disease-free controls, in each disease model, and the interaction between FGF23 X disease effect for the anti-GBM and FSGS groups. Gene set enrichment analysis was performed with a focus on the immune system. Results Anti-GBM mice showed a 45 ± 27% GFR decline (mean ± SD) compared to baseline, whereas controls showed an GFR increase of 11 ± 36% (p < 0.01). Kidney histology revealed an interstitial infiltrate. The FSGS model showed elevated serum creatinine and albuminuria, and hypercellularity in some glomeruli. Mice of the adenine model showed progressively increased blood urea nitrogen concentrations starting after 2 weeks, up to a 3-fold increase at week 14. Histology revealed interstitial fibrosis and tubular atrophy. Bulk RNAseq revealed proinflammatory transcriptional signatures after FGF23 treatment in all disease models, regardless of which timepoint or model: In the anti-GBM model, Hallmark gene sets of inflammatory response, interferon-α response, interferon-β response and allograft rejection were significantly increased after 6 days of FGF23 treatment, whereas disease-free controls showed no significantly changed immune gene sets after 6 days of FGF23. In FSGS mice, none of the Hallmark gene sets were changed after 1 FGF23 injection, but top individual gene expression affected by 1 FGF23 injection were an increased proinflammatory transcription factor Cebpb and an increased DNA damage transcript Dclre1b. Finally, the PCKS of adenine model revealed no significant Hallmark gene sets, but the two genes with differential expression were a proinflammatory macrophage/fibroblast chemokine Ccl4 (increased) and an immunoglobulin heavy variable Ighv2-2 (decreased). Conclusion FGF23-driven patterns of proinflammatory gene expression were observed in three experimental models of kidney disease, both in vivo and ex vivo assessment of FGF23 signaling, thus excluding effects of FGF23 on other organs. As these findings were limited to transcriptional analyses, the present data warrant further confirmation and exploration of FGF23 as a pathogenic agent in kidney disease.

#2842 Increased incidence of anti-glomerular basement membrane disease in Madrid in the past two decades

Abstract Background and Aims Recently, epidemiological changes have been identified in the incidence of anti-glomerular basement membrane (GBM) in different European regions, reporting an increased incidence in population-based studies in Ireland and Denmark, possibly due to demographic changes and exposure to environmental triggers, since the evidence of spatial and temporal clustering of cases suggests that environmental factors could be playing a role in this trend. The aim of our study was to evaluate the changes in incidence of anti-GBM disease in the past two decades in two different urban areas in Madrid (North and Southwest), identify possible environmental triggers, and analyse temporal and within-area differences in presentation and outcome of the disease. Method We performed a retrospective observational study using data between 2006 and 2022 from the hospital coding databases and laboratory databases of two hospitals in Madrid covering a population of 884000 residents. We collected data from patients who were diagnosed with anti-GBM disease with confirmed positive anti-GBM antibodies and renal and/or pulmonary manifestations. We excluded patients with positive anti-GBM antibodies without clinical manifestations suggestive of the disease. Incidence was described as per 100000 person-years at risk, and 95% confidence intervals were computed assuming a Poisson distribution. In order to detect changes in incidence, we divided the analysis into three time periods: 2006-2010, 2011-2016 and 2017-2022. We also compared the incidence before and after the onset of COVID-19 pandemic in Madrid (March 2020). Demographic data, clinical data at presentation, previous exposure to environmental factors (smoking, exposure to hydrocarbons, infections, vaccination), and treatments received and outcome was collected. Renal survival was defined as a state free from renal replacement therapy. Results During the 17-year study period, 26 cases of anti-GMN disease were identified (incidence rate 2.94 per 100000 persons); with a mean age of 52 ± 26 years at presentation, and 53.6% were females. 30.8% of patients were double-seropositive for ANCA and anti-GBM, 42.3% presented only renal involvement, 3.8% with only pulmonary involvement, and 53.8% with both renal and pulmonary involvement. At presentation, 19.2% of patients required mechanical ventilation and 65.4% required renal replacement therapy. After induction treatment, 13 patients (50%) remained on maintenance dialysis. After a median follow-up of 33 months, 46.2% patients died. Renal and patient survival after 1 year was 30.8% and 73.1% respectively. The incidence rate gradually increased from time periods 2006-2010 to 2017-2022, from 1.81 cases per 100000 persons (CI95% 0.78-3.57) to 2.83 cases per 100000 persons (CI95% 1.58-4.66) (OR 1.56, CI95%0.66-3.69, p = 0.30). We observed that the incidence rate significantly increased from 1.13 cases per 100000 persons (95% CI 0.62-1.90) before March 2020 to 4.53 cases per 100000 persons (95% CI 2.34-7.90) after the onset of the COVID-19 pandemic (OR 4, P < 0.001). Serum creatinine at presentation was significantly lower in cases diagnosed after COVID-19 (5.09 ± 4 vs 8.7 ± 3.9 mg/dl, p = 0.037). We found no differences within time periods in demographic data, previous exposure to environmental triggers, presence of double-seropositivity, or treatments received or patient survival after 1 year. However, we found that renal survival after 1 year has improved from 0% in 2006-2010 to 46.7% in 2017-2022 (p = 0.023) and 14.3% pre-COVID to 50% post-COVID (p = 0.049). Conclusion There is a gradual increase in the incidence rate of anti-GBM disease in our population, which has markedly increased after the COVID-19 pandemic, with a significantly lower serum creatinine at presentation with improved renal survival. We did not find any changes in the rate of exposure to known environmental triggers within time periods. These findings suggest that the rising incidence may be attributable to an increased awareness and diagnosis of anti-GBM disease, which leads to a better renal survival.

Transcriptome Analysis of BAFF/BAFF-R System in Murine Nephrotoxic Serum Nephritis.

Chronic kidney disease (CKD) is an emerging cause for morbidity and mortality worldwide. Acute kidney injury (AKI) can transition to CKD and finally to end-stage renal disease (ESRD). Targeted treatment is still unavailable. NF-κB signaling is associated with CKD and activated by B cell activating factor (BAFF) via BAFF-R binding. In turn, renal tubular epithelial cells (TECs) are critical for the progression of fibrosis and producing BAFF. Therefore, the direct involvement of the BAFF/BAFF-R system to the pathogenesis of CKD is conceivable. We performed non-accelerated nephrotoxic serum nephritis (NTN) as the CKD model in BAFF KO (B6.129S2-Tnfsf13btm1Msc/J), BAFF-R KO (B6(Cg)-Tnfrsf13ctm1Mass/J) and wildtype (C57BL/6J) mice to analyze the BAFF/BAFF-R system in anti-glomerular basement membrane (GBM) disease using high throughput RNA sequencing. We found that BAFF signaling is directly involved in the upregulation of collagen III as BAFF ko mice showed a reduced expression. However, these effects were not mediated via BAFF-R. We identified several upregulated genes that could explain the effects of BAFF in chronic kidney injury such as Txnip, Gpx3, Igfbp7, Ccn2, Kap, Umod and Ren1. Thus, we conclude that targeted treatment with anti-BAFF drugs such as belimumab may reduce chronic kidney damage. Furthermore, upregulated genes may be useful prognostic CKD biomarkers.

Pathogenesis of Pulmonary Manifestations in ANCA-Associated Vasculitis and Goodpasture Syndrome.

Pulmonary manifestations of vasculitis are associated with significant morbidity and mortality in affected individuals. They result from a complex interplay between immune dysregulation, which leads to vascular inflammation and tissue damage. This review explored the underlying pathogenesis of pulmonary involvement in vasculitis, encompassing various forms such as granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and anti-GBM disease. Mechanisms involving ANCA and anti-GBM autoantibodies, neutrophil activation, and neutrophil extracellular trap (NETs) formation are discussed, along with the role of the complement system in inducing pulmonary injury. Furthermore, the impact of genetic predisposition and environmental factors on disease susceptibility and severity was considered, and the current treatment options were presented. Understanding the mechanisms involved in the pathogenesis of pulmonary vasculitis is crucial for developing targeted therapies and improving clinical outcomes in affected individuals.

Unravelling the Link between the Gut Microbiome and Autoimmune Kidney Diseases: A Potential New Therapeutic Approach.

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may systemically induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins by penetrating the gut epithelial barrier. Once in the blood stream, these pro-inflammatory mediators activate immune cells, which release pro-inflammatory molecules, many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes/Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including lupus nephritis, MPO-ANCA vasculitis, and Goodpasture's syndrome. Therapies that enhance SCFA-producing bacteria in the gut have powerful therapeutic potential. Dietary fiber is fermented by gut bacteria which in turn release SCFAs that protect the gut barrier, as well as modulating immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability

This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient’s kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.

364 Atypical case of anti-glomerular basement membrane disease

364 Atypical case of anti-glomerular basement membrane disease

Urban Agroecosystems in Dynamic Yamuna River Sandbars in Delhi, Capital City of India

Present paper studies urban agroecosystems on Yamuna River sandbars (islands) in Delhi using GIS. These sandbars formally come under local administration and are used by people for different activities like agriculture, fishing, collection of various types of grasses, and grazing of livestock. Cheap laborers from different states of India migrate to the sandbars for seasonal employment. The crops grown by farmers include tomatoes, pumpkins, bottle gourds, ridge gourds, and bitter gourds. Tomatoes are grown on the maximum area of land on the sandbars. The products are sold at different nearby markets according to requirements. These small and fragile agroecosystems have inputs like seeds, human labor/hours, fertilizers, water, fuels, etc., and outputs like crops, grasses, fish, milk, etc. For a long time, people have been interested in these landscapes because; i) the deposits along the Yamuna are fertile and therefore appropriate for farming, (ii) the growth of natural vegetation/fodder species (which includes many types of grasses) makes them good pastures, (iii) the river banks along the attached sandbars provide space for the washermen, (_dhobi-ghat)_, (iv) even if the government officials abandon the slums/activities on these sandbars, the people involved in them could re-build it in no time, and (v) none of the sandbar dwellers were paying any rent/lease for the activities they are carrying out on the sandbars. The pastoralists (_gujjar)_ do not seem to have to pay anything to the claimant. On the other hand, the farmers do have to pay for cultivating on the sandbars.

Urban Agroecosystems in Dynamic Yamuna River Sandbars in Delhi, Capital City of India

Present paper studies urban agroecosystems on Yamuna River sandbars (islands) in Delhi using GIS. These sandbars formally come under local administration and are used by people for different activities like agriculture, fishing, collection of various types of grasses, and grazing of livestock. Cheap laborers from different states of India migrate to the sandbars for seasonal employment. The crops grown by farmers include tomatoes, pumpkins, bottle gourds, ridge gourds, and bitter gourds. Tomatoes are grown on the maximum area of land on the sandbars. The products are sold at different nearby markets according to requirements. These small and fragile agroecosystems have inputs like seeds, human labor/hours, fertilizers, water, fuels, etc., and outputs like crops, grasses, fish, milk, etc. For a long time, people have been interested in these landscapes because; i) the deposits along the Yamuna are fertile and therefore appropriate for farming, (ii) the growth of natural vegetation/fodder species (which includes many types of grasses) makes them good pastures, (iii) the river banks along the attached sandbars provide space for the washermen, (_dhobi-ghat)_, (iv) even if the government officials abandon the slums/activities on these sandbars, the people involved in them could re-build it in no time, and (v) none of the sandbar dwellers were paying any rent/lease for the activities they are carrying out on the sandbars. The pastoralists (_gujjar)_ do not seem to have to pay anything to the claimant. On the other hand, the farmers do have to pay for cultivating on the sandbars.

Goodpasture syndrome: An updated overview for healthcare professionals

Background: Goodpasture syndrome is an autoimmune disorder characterized by the presence of anti-glomerular basement membrane (anti-GBM) antibodies, leading to significant lung and kidney complications, particularly pulmonary hemorrhage and glomerulonephritis. The disease has a poor prognosis if not promptly treated, making early identification and intervention crucial. Aim: This article aims to provide an updated overview of Goodpasture syndrome, highlighting its etiology, epidemiology, pathophysiology, diagnosis, and treatment approaches, to enhance healthcare professionals' understanding and management of this condition. Methods: A comprehensive review of current literature on Goodpasture syndrome was conducted, focusing on its clinical presentation, histopathological findings, and advancements in diagnostic techniques. The article discusses relevant immunological aspects, genetic predispositions, and the significance of serological testing in diagnosis. Results: The incidence of Goodpasture syndrome is estimated at 0.5 to 1.8 cases per million annually, with a bimodal age distribution. Genetic factors, particularly the presence of specific human leukocyte antigens (HLAs), play a significant role in disease susceptibility. The pathophysiology involves circulating autoantibodies targeting type IV collagen, leading to crescentic glomerulonephritis and pulmonary damage. Renal biopsy remains the gold standard for diagnosis, with immunofluorescence microscopy revealing characteristic linear immunoglobulin deposits.

Study on the prevalence of gastrointestinal nematodes in goats from the Rupandehi district in Nepal

Goats play an important role in the livelihood of the farmer but their frequent encounter with gastrointestinal nematodes causes retarded growth, mortality, and production losses. A cross-sectional descriptive study was conducted between August and November 2023 to determine the prevalence, level of infections, and its association with various risk factors. A total of 350 fecal samples of goats were collected per rectally using the purposive sampling method from the smallholder and commercial farm of Tilottama Municipality, Rupandehi, Nepal. The collected sample was subjected to floatation and the McMaster technique for qualitative and quantitative examination with saturated NaCl solution. Data was entered in MS Excel 2013 and analysis was performed in SPSS version 25. Out of 350 samples, 242 (69.14%) were found to be positive for gastrointestinal nematodes among which the Strongyle group (60%) including Haemonchus spp., Oesophagostomum spp., Trichostrongylus spp., Bunostomum spp.), Strongyloides sp. (38.57%), and Trichuris spp. (11.14%). The EPG of the total positive sample was 1352 (192.610). Statistically, there was a significant association among the smallholder vs commercial for prevalence rates (p = 0.000242) rates and EPG (p = 0.003). The statistical difference was also observed based on deworming status for the prevalence of nematodes and EPG count (p = 0.016). The practice of good housing, grazing and pasture management, feeding of supplements, and deworming at a regular interval must be maintained to promote growth, minimize mortality & production losses, and maximize the returns from animals.

Efficacy of rituximab for patients with anti-glomerular basement membrane disease.

Efficacy of rituximab for patients with anti-glomerular basement membrane disease.

Evaluation of the Risk Prediction Models in Predicting Kidney Outcomes in Antiglomerular Basement Membrane Disease

A previous study showed that the renal risk score (RRS) was transferrable to antiglomerular basement membrane (anti-GBM) disease and proposed a risk stratification according to the need of renal replacement therapy (RRT) and the percentage of normal glomeruli (N). Herein, we analyzed the risk factors associated with kidney outcomes in patients with biopsy-proven anti-GBM disease and evaluated these 2 prognosis systems. A total of 120 patients with biopsy-proven anti-GBM disease with complete clinicopathologic and outcome data were analyzed. The median time to kidney biopsy was 41 days (interquartile range [IQR]: 22-63 days). RRT and N were the only independent predictors of end-stage kidney disease (ESKD). Patients with N≥10% were more likely to achieve ESKD-free outcomes, even in the subcohort of patients who underwent posttreatment biopsies (P< 0.001). N and serum creatinine at presentation (cut-off values 750 μmol/l and 1300 μmol/l) were 2 independent factors for predicting kidney recovery. The RRS and the risk stratification tool exhibited predictive value for ESKD and could be transferred to patients with kidney biopsy following treatment (Harrell's C statistic [C]= 0.738 and C= 0.817, respectively). However, a cross-over of outcomes among groups was observed in the risk stratification tool in long-term follow-up, when patients with RRT and N≥10% achieved better kidney outcomes than those without RRT but N<10%. Normal glomeruli percentage, even posttreatment, was a strong indicator for kidney outcomes, especially on long-term prognosis. Serum creatinine is a predictor for kidney recovery, independent of biopsy findings. The risk stratification tool for kidney survival was transferrable to patients with anti-GBM disease with biopsy following treatment in our cohort; however, this needs further validations for long-term outcomes.

Bullous Variant of Central Serous Chorioretinopathy in Goodpasture's Disease - A Case Report and Review of Literature.

To describe a case of bullous variant of central serous chorioretinopathy (CSR) in Goodpasture's disease (GD) compared to an identical twin without GD, and summarize the literature on ocular manifestations of GD. Interventional/observational case report and literature review. A 46-year-old white female with a history of GD presented with decreased vision. She demonstrated bilateral multifocal pigment epithelial detachments and a large inferior exudative retinal detachment in the left eye consistent with bilateral CSR with bullous variant CSR (bvCSR) in the left eye. Despite treatment, her disease remained refractory, with final VA of 20/200 in the left eye. The patient's identical twin sister did not have GD and demonstrated milder CSR on presentation with a more typical, self-limited disease course. Her final VA was 20/20 bilaterally. GD is associated with severe manifestations of CSR (exudative RD). Additional studies focusing on the association between GD and CSR severity may be of interest.

Serum sulfatide level is associated with severe systemic vasculitis with kidney involvement.

Sulfatides are a type of sulfated glycosphingolipid that are secreted with lipoproteins into the serum. These molecules are involved in the inflammatory pathway of vessels in addition to coagulation and platelet aggregation. Previous studies have proposed that sulfatides play a pivotal role in regulating inflammation-related disorders. Systemic vasculitis (SV) diseases are generally caused by autoimmune diseases and often involve kidney vasculitis, which may lead to rapidly progressive kidney dysfunction and end-stage kidney disease. Our earlier pilot study revealed that the level of serum sulfatides (SSs) was significantly decreased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), a representative disease-causing SV with kidney involvement (SVKI), especially in patients exhibiting active crescentic findings on kidney biopsy. To further explore the clinical significance of an association between SS and SVKI, we analyzed and compared the SS level of patients with various SVKI diseases in this retrospective cohort study. Among patients admitted to our hospital between 2008 and 2021, we ultimately enrolled 26 patients with IgA vasculitis (IgAV), 62 patients with AAV, and 10 patients with anti-glomerular basement membrane disease (GBM) as examples of SVKI diseases, as well as 50 patients with IgA nephropathy (IgAN) and 23 donors for living kidney transplantation as controls. The mean ± standard deviation SS level in the donor, IgAN, IgAV, AAV, and GBM groups was 8.26 ± 1.72, 8.01 ± 2.21, 6.01 ± 1.73, 5.37 ± 1.97, and 2.73 ± 0.99 nmol/mL, respectively. Analysis of patients in the SVKI disease group showed that those with the crescentic class kidney biopsy finding exhibited a significantly lower SS level than did those with other class biopsy features. Additionally, the SS level had a higher detection ability for SVKI patients with crescentic class kidney biopsy findings (area under the receiver operating characteristic curve 0.90, 95% confidence interval 0.82-0.99) than did several other predictor candidates. Our results indicate that the SS level is decreased in more severe SVKI diseases and may be associated with active glomerular lesions in SVKI kidney biopsy samples.

Laminin-521: a novel target for pathogenic autoantibodies in anti–glomerular basement membrane disease

Anti-glomerular basement membrane (anti-GBM) disease is typically characterized by autoimmunity against the α3 chain of type IV collagen. Rarely, circulating autoantibodies are not detected. These atypical cases follow a more indolent clinical course, and underlying mechanisms, including alternative target antigens, require investigation. In this issue of Kidney International, Kuang etal. describe a case of anti-GBM disease with autoantibodies against the GBM component laminin-521 and demonstrate that laminin-521 is pathogenic in a rat model of anti-GBM glomerulonephritis.

The Immunobiological Agents for Treatment of Antiglomerular Basement Membrane Disease.

Combination therapy with glucocorticoids, cyclophosphamide, and plasmapheresis is recommended as the standard treatment for anti-glomerular basement membrane (anti-GBM) disease, but the prognosis of this disease remains poor. Several immunobiological agents have been administered or are expected to be useful for anti-GBM disease in light of refractory disease or the standard treatments' tolerability. Many data regarding the use of biologic agents for anti-GBM disease have accumulated, verifying the effectiveness and potential of biologic agents as a new treatment option for anti-GBM disease. Tumor necrosis factor (TNF) inhibitors were shown to be useful in animal studies, but these agents have no clinical use and were even shown to induce anti-GBM disease in several cases. Although the efficacy of the TNF-receptor antagonist has been observed in animal models, there are no published case reports of its clinical use. There are also no published reports of animal or clinical studies of anti-B-cell-activating factor, which is a member of the TNF family of agents. Anti-interleukin (IL)-6 antibodies have been demonstrated to have no effect on or to exacerbate nephritis in animal models. Anti-C5 inhibitor was observed to be useful in a few anti-GBM disease cases. Among the several immunobiological agents, only rituximab has been demonstrated to be useful in refractory or poor-tolerance patients or small uncontrolled studies. Rituximab is usually used in combination with steroids and plasma exchange and is used primarily as an alternative to cyclophosphamide, but there is insufficient evidence regarding the efficacy of rituximab for anti-GBM disease, and thus, randomized controlled studies are required.

Pneumorenal Syndrome Complicating ANCA-Negative Pauci-Immune Vasculitis Associated with Atypical Mycobacteriosis: Case Report

Among the forms of pneumorenal syndrome (PRS), one of the most urgent is characterized by the combination of diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis (RPGN). In 90% of cases, it is the manifestation of an autoimmune disease, such as pauci-immune vasculitis with anti-neutrophil cytoplasmic antibodies (ANCA) or Goodpasture's disease with the presence of antibodies directed against the basement membrane of the glomerular and alveolar capillaries (anti-GBM). These antibodies are absent in approximately 10% of cases with histological confirmation in the context of rare clinical situations. We report a case of a 66-year-old patient, with a history of alcoholism and active smoking, who was admitted to the hospital for respiratory distress with hemoptysis. The admission assessment showed severe renal failure requiring hemodialysis upon admission. ANCA and anti-GBM, as well as all other autoantibodies were negative. A renal biopsy revealed pauci-immune extra-capillary glomerulonephritis with the majority of chronic lesions. The orientation of the diagnostic approach in search of other causes of pauci-immune vasculitis with negative antibodies has been initiated. He was treated with glucocorticoids in combination with cyclophosphamide. The initial evolution was marked by the improvement of respiratory symptoms and a less considerable recovery of renal function. PRS can develop without the presence of ANCA or other autoantibodies. The diagnosis is then made by histology. Renal damage, such as extra-capillary glomerulonephritis (GN), is more severe and has a very poor prognosis with a high risk of mortality. The absence of ANCA should never delay diagnosis and treatment.