ANCA-associated Glomerulonephritis Research Articles

Autoantibodies Targeting Nephrin in Podocytopathies.

Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear. We conducted a multicenter study to analyze antinephrin autoantibodies in adults with glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, antineutrophil cytoplasmic antibody-associated glomerulonephritis, and lupus nephritis, as well as in children with idiopathic nephrotic syndrome and in controls. We also created an experimental mouse model through active immunization with recombinant murine nephrin. The study included 539 patients (357 adults and 182 children) and 117 controls. Among the adults, antinephrin autoantibodies were found in 46 of the 105 patients (44%) with minimal change disease, 7 of 74 (9%) with primary focal segmental glomerulosclerosis, and only in rare cases among the patients with other conditions. Of the 182 children with idiopathic nephrotic syndrome, 94 (52%) had detectable antinephrin autoantibodies. In the subgroup of patients with active minimal change disease or idiopathic nephrotic syndrome who were not receiving immunosuppressive treatment, the prevalence of antinephrin autoantibodies was as high as 69% and 90%, respectively. At study inclusion and during follow-up, antinephrin autoantibody levels were correlated with disease activity. Experimental immunization induced a nephrotic syndrome, a minimal change disease-like phenotype, IgG localization to the podocyte slit diaphragm, nephrin phosphorylation, and severe cytoskeletal changes in mice. In this study, circulating antinephrin autoantibodies were common in patients with minimal change disease or idiopathic nephrotic syndrome and appeared to be markers of disease activity. Their binding at the slit diaphragm induced podocyte dysfunction and nephrotic syndrome, which highlights their pathophysiological significance. (Funded by Deutsche Forschungsgemeinschaft and others.).

#2958 Can the Kidney Failure Risk Equation (KFRE) be used in ANCA associated glomerulonephritis?

Abstract Background and Aims The Kidney Failure Risk Equation (KFRE) provides a 2 and 5 year probability of treated kidney failure for a patient with chronic kidney disease (CKD) stage 3a to 5. KFRE has been validated in over 30 countries, including the United Kingdom (UK) and has become a useful tool to aid clinical decision making [1]. However there has been limited validation to determine if KFRE can be used in primary renal pathologies such as ANCA associated glomerulonephritis (AAGN). We conducted a retrospective cohort study of patients with AAGN at a single centre in Lancashire, UK to determine if KFRE accurately predicts end stage kidney disease (ESKD). Method Patients diagnosed with AAGN between 2009 and 2018 were screened for inclusion. Exclusion criteria included mortality within 6 months of diagnosis, those that remained dialysis dependent 6 months after diagnosis, transfer out of area, eGFR >60 ml/min/1.73 m2 and missing biochemical results required to calculate KFRE. Baseline and clinical characteristics were collected. The UK 4-variable KFRE was calculated at 6 months (±3 months) and 18 months (±3 months) after initial diagnosis of AAGN (1). Clinical outcomes including ESKD (dialysis or transplantation) were recorded. Statistical analysis was performed. The median and interquartile range were used for continuous variables and frequency and percentage for absolute values. The median and interquartile range were calculated for KFRE. The area under the received operator characteristic curve (AUC) was used to calculate discrimination of KFRE. Results Of the 150 patients screened, 78 patients were included in this retrospective analysis. Median age at diagnosis was 67 years (IQR 61-74 years). Forty one (53%) males and 37 (47%) females were included in the study. Forty two (53.8%) patients had positive anti-MPO antibodies, 29 (37.2%) had anti-PR3 antibodies and 7 (9.0%) had seronegative AAGN. 15 of 78 patients required dialysis or transplantation within the study period assessed. KFRE was calculated at 6 months (± 3 months) ; the median 2 year risk KFRE score was 2% (IQR 0.3-5%) and median 5 year KFRE score was 7.1% (IQR 1.1-17.6%) (Fig. 1). KFRE was calculated at 18 months (± 3 months) ; the median 2 year risk KFRE score was 0.7% (IQR 0.4–2.7%) and median 5 year KFRE score was 2.1% (IQR 0.7–9.5%). In terms of discrimination for KFRE calculated 6 months after diagnosis, in the 2 year analysis, the AUC was 0.74 (95% CI 0.55-0.92) and in the 5 year analysis, the AUC was 0.73 (95% CI 0.55-0.90). When KFRE was calculated 18 months after diagnosis, in the 2 year analysis, the AUC was 0.75 (95% CI 0.30-1) and in the 5 year analysis, the AUC was 0.81 (95% CI 0.50-1). Conclusion While KFRE is a thoroughly validated and widely adopted tool in CKD patients, its application in primary renal pathologies, such as AAGN, is yet to be determined. We have shown that KFRE provides fair discrimination, as early as 6 months after initial diagnosis and may provide future clinical utility in AAGN patients that have achieved stable remission. Current tools to risk stratify AAGN patients require histological parameters which is not always possible to achieve and further work in predicting the prognosis of glomerular diseases is needed. This study was limited by the single centre and small cohort but further analysis and validation on a larger multi-centre cohort is needed before KFRE can be considered for clinical use in AAGN patients.

#1355 Albuminuria after Induction Treatment and Kidney Prognosis in ANCA-associated Glomerulonephritis

Abstract Background and Aims Persisting proteinuria has been associated with worse kidney outcomes in ANCA-associated glomerulonephritis (AAGN). However, it remains unclear whether this reflects damage from the initial injury or ongoing inflammation. Method A retrospective, single centre study of biopsy-proven AAGN. The group “albuminuria” was defined as urine albumin-to-creatinine ratio (ACR) more than 300 mg/g and the group “no albuminuria”, defined as ACR less than or equal to 300 mg/g at 6 months. We sought the clinical and histopathological characteristics from both the initial and any subsequent biopsies, and long-term kidney outcomes stratified by albuminuria levels. Results 218 patients were included. Within the first six months, 28 (13%) had either died or progressed to end-stage kidney disease (ESKD). Among the remaining 190 patients, 37% had an ACR>300 mg/g at 6 months. The albuminuria group more frequently presented with a Berden mixed or crescentic class and had higher glomerular activity on the initial biopsy. They were also more often male [odds ratio (OR) 2.69; 95% CI 1.13-6.41], of younger age (OR 0.96; 95% CI, 0.93 to 0.99) and had fewer normal glomeruli in the biopsy (OR 0.96; 95% CI, 0.93 to 0.99) compared to the group without albuminuria. Over the initial 5-year period, the recovery in glomerular filtration rate (GFR) was lower in the albuminuria group (adjusted mean difference in delta GFR −12.5 ml/min per 1.73 m2; 95% CI, −15.8 to −9.1). In multivariable analysis, ACR greater than 300 mg/g was associated with a higher risk of ESKD, even after adjusting for age, Berden classification and GFR at diagnosis (Hazard ratio 7.25; 95% CI, 1.62 to 32.47). Conclusion In a well-defined cohort of AAGN, one third of the patients, primarily younger males with a lower percentage of normal glomeruli, had persisting albuminuria after induction treatment which was associated with worse kidney outcomes independent of Berden class and GFR at diagnosis.

#1121 Identification of kidney transcripts associated with prognosis in ANCA-associated glomerulonephritis

Abstract Background and Aims Kidney involvement in ANCA-associated vasculitis (AAV-GN) predicts poor patient and kidney survival. Deciphering the transcriptomic landscape in AAV-GN may provide insights into pathogenic mechanisms or identify biomarkers for refining diagnosis and/or prognosis, which would help stratify risk and tailor therapeutic management. We aimed to investigate the potential prognostic value of kidney transcripts associated with kidney survival. Method This study included adult patients with AAV-GN from the French Maine-Anjou Registry. Immune gene transcript analysis was performed on RNA extracted from 97 AAV-GN kidney biopsies using NanoString technology. Transcripts of interest were selected, and their prognostic performance was assessed with respect to current histological-based classifications. Following the identification of a possible role for clusterin (CLU), the relationship between serum CLU and prognosis was assessed. Results Among the 750 evaluated transcripts, we identified a 4-gene signature (XRCC6, PRKCD, TEK, and CLU) that was strongly associated with kidney survival (Fig. 1A). This signature predicted kidney survival better than histological-based classifications (global C-Index 0.87 vs. 0.65 for Berden classification or 0.81 for Renal Risk Score, with better time-dependent AUC and Brier scores, especially beyond 1 year after diagnosis) (Fig. 1B). Among these 4 transcripts, the expression level of the CLU transcript had the highest correlation with glomerular involvement, kidney function at diagnosis, and kidney survival. Serum CLU levels were associated with kidney survival, especially when assessed at 6 months from diagnosis (Fig. 1C, P = .023). Conclusion Transcriptomic analysis of kidney biopsies of AAV-GN identified potential transcripts that may improve prediction of kidney survival. This transcriptomic signature may help us gain a deeper understanding of the AAV-GN pathogenesis and provide insights for developing new therapeutic options.

Clinicopathological characteristics of pediatric ANCA-associated glomerulonephritis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and glomerulonephritis is uncommon in children. We sought to characterize the histological and clinical features of the disease and report on risk factors for adverse outcomes in a pediatric cohort. Retrospective single-center cohort of all pediatric (< 20years) patients diagnosed with ANCA-associated glomerulonephritis (AAGN) by kidney biopsy between 2002 and 2022 at Johns Hopkins University. Histological and clinical features were extracted from the medical record. Clinical, laboratory, and histological findings were analyzed to determine the association with kidney failure (KF) and/or death. A total of 17 patients were identified (GPA n = 7, MPA = 10) with a median age of 15years (IQR 12-17) at presentation, a slight female predominance (59%), with seven patients reaching the composite outcome of death (n = 1) or kidney failure (n = 6). There was no difference in presenting clinical symptoms or extra-renal manifestations between the two groups. Univariable Cox regression identified several factors associated with an increased hazard of endpoint including the degree of global or segmental sclerosis, interstitial fibrosis and tubular atrophy (IFTA), C3 and C1q staining, presence of subendothelial deposits, and proteinuria. Multivariable regression was not performed due to the small sample size. We saw a trend towards increased utilization of plasma exchange and a decrease in cyclophosphamide utilization in the more recent era. There was no association between treatment modality and outcome. Pediatric AAGN is a rare disease associated with significant morbidity. We identified glomerulosclerosis and IFTA on histology, and proteinuria on initial presentation as risk factors for KF/death.

The value of the current histological scores and classifications of ANCA glomerulonephritis in predicting long-term outcome

Abstract Background and Aims Three different histological scores- histopathologic classification (Berden), Renal Risk Score (RRS) and the Mayo Clinic Chronicity Score (MCCS) for ANCA associated glomerulonephritis (ANCA-GN) were compared to evaluate their association with patient and kidney prognosis of ANCA-GN. Methods Patients aged &amp;gt; 18 years with at least one year of follow-up and biopsy-proven ANCA-GN entered this retrospective study. Renal biopsies were classified according to Berden's classification, RRS and MCCS. The first endpoint was end-stage kidney disease (ESKD), defined as chronic dialysis or glomerular filtration rate (GFR) &amp;lt;15 ml/min/1.73m2. The second endpoint was ESKD or death. Results Of 152 patients 84 were males, with median age of 63.8 years and followed for 46.9 (IQR 12.8–119) months, 59 (38.8%) reached the first endpoint and 20 died. The Kaplan-Meier curves showed that Berden and RRS were associated with first (Berden: p = 0.004, RRS: p &amp;lt; 0.001) and second endpoint (Berden: p = 0.001, RRS: p &amp;lt; 0.001), MCCS with the first endpoint only when minimal + mild vs moderate + severe groups were compared (p = 0.017) and with the second endpoint (p &amp;lt; 0.001). Among the clinical/histological presentation features, arterial hypertension (OR = 2.75, CI = 1.50–5.06, p = 0.0011), serum creatinine (OR = 1.17, CI = 1.09–1.25, p &amp;lt; 0.0001), and the percentage of normal glomeruli (OR = 0.97, CI = 0.96–0.99, p = 0.009) were the independent predictors of ESKD at multivariate analysis (MA). When the three scores were included in MA, RRS (OR = 2.21, CI = 1.15–4.24, p = 0.017) and MCCS (OR = 2.03, CI = 1.04–3.95, p = 0.037), remained predictive of ESKD but Berden (OR = 1.17, CI = 0.62–2.22, p = 0.691) did not. Conclusion RRS and MCCS scores were independent predictors of kidney survival together with high serum creatinine and arterial hypertension at diagnosis, while Berden classification did not.

Slowly Progressive ANCA-associated Glomerulonephritis with Strong Mesangial MPO Deposits Following a Diagnosis of Interstitial Lung Disease.

An elderly woman showed positive conversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCAs) following the diagnosis of interstitial lung disease (ILD) and glomerular hematuria and subsequently experienced slowly progressive glomerulonephritis. A kidney biopsy revealed chronic damage and necrotizing crescentic glomerulonephritis with mesangial MPO deposits. After corticosteroid treatment, the patient's urinalysis results and MPO-ANCA titers almost normalized and her renal function stabilized. This case is similar to recently reported cases of slowly progressive ANCA-associated glomerulonephritis. ILD likely triggered the production of MPO-ANCAs, and the accumulation of MPO deposits in the glomeruli may have contributed to the progression of her renal disease.

Myeloperoxidase-Associated Membranous Nephropathy in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis

IntroductionAnti-neutrophil cytoplasmic antibody (ANCA)–associated glomerulonephritis (GN) is characterized by pauci-immune crescentic GN. Although myeloperoxidase ANCA-associated GN (MPO-ANCA GN) with membranous nephropathy (MN), where bright granular capillary myeloperoxidase (MPO) and immunoglobulin G (IgG) staining along the glomerular basement membrane (GBM) is present, has been reported; however, its clinicopathological features remain unclear. MethodsWe investigated 7 MPO-ANCA GN with MN and 11 control cases (6 MPO-ANCA GN and 5 primary MN cases). Proteomics of laser microdissected glomeruli followed by immunohistochemical analysis was performed to identify causal antigens in MPO-ANCA GN with MN. We described the clinicopathological features of MPO-associated MN compared with those of MPO-ANCA GN and primary MN. ResultsWe detected proteomic MPO and granular capillary MPO deposits in all MPO-ANCA GN with MN cases. Confocal microscopy revealed MPO and IgG co-localization along the GBM. MPO-associated MN clinicopathological features include greater proteinuria, a higher fibrous crescent rate, and a lower MPO-ANCA titer than MPO-ANCA GN. The estimated glomerular filtration rate and urinary protein excretion were lower in MPO-associated MN than in primary MN. ConclusionMPO-associated MN, a unique type of secondary MN where MPO serves as the causal antigen, is a subset of MPO-ANCA GN with MN. Prolonged periods of MPO-ANCA GN and a low MPO-ANCA titer might be related to MPO-associated MN development.

A case of seronegative microscopic polyangiitis following the diagnosis of renal pelvic carcinoma.

The incidence rate of malignancy in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is higher than that in the general population. Malignancy has been indicated to be a risk factor or inducer of AAV. Herein, we report the case of a healthy 84-year-old man with seronegative microscopic polyangiitis (MPA) after thediagnosis of renal pelvic carcinoma. Four weeks before admission, his estimated glomerular filtration rate (eGFR) was 85ml/min/1.73m2, and nohematuria or proteinuria was detected. Renal biopsy on admission revealed invasive urothelial carcinoma of the right renal pelvis. On day 15, his eGFR decreased to 30ml/min/1.73m2 without any incitement. The renal specimen extracted via right robot-assisted nephroureterectomy indicated the presence of ANCA-associated glomerulonephritis. On day 37, urinary protein/urinary creatinine level of 6.48g/gCre, serum albumin level of 2.1mg/dL, and eGFR of 20ml/min/1.73m2 indicated the presence of nephrotic syndrome. His blood sputum was analyzed via chest computed tomography, which revealed alveolar hemorrhage. Although his myeloperoxidase-ANCA was negative, he was diagnosed with MPA based on the 2022 American College of Rheumatology/European League Against Rheumatism classification criteria. This is the first case report of MPA orAAV complicated with renal pelvic carcinoma. The clinical indicators demonstrated that renal pelvic carcinoma preceded the onset of MPA. The spatial proximity of both diseases indicated that renal pelvic carcinoma had some influence on MPA development via the mechanism of inflammatory cytokines or neutrophil extracellular traps. Our report may be useful in elucidating the mechanism of MPA development.

The prognostic value of two histopathologic classification models of ANCA-associated glomerulonephritis: a prospective study.

Berden Classification and anti-neutrophil cytoplasmic antibody (ANCA) Renal Risk Score are classification models for rating renal histology and predicting outcome in patients with ANCA-associated Vasculitis/Glomerulonephritis (AAV/GN). In the present study we compare their ability to predict renal function outcome in short- and long-term follow up. Patients with an initial diagnosis of AAV/GN based on kidney biopsy were classified according to Berden and Renal Risk Score, started on the same treatment protocol, and were followed prospectively for up to 60 months. Renal function was recorded at 3mo(T3), 6mo(T6) and 60mo(T60), and results were compared to both classification systems. Ninety four AAV/GN patients, M/F = 36/58, age = 60.05 (18-82)yrs were included. Based on Berden classification, patients grouped as Focal (n = 24), Crescentic (n = 35), Mixed (n = 21) and Sclerotic (n = 14), had significant differences in estimated glomerular filtration rate (eGFR) only at T3, while the percentage of those requiring hemodialysis differed at T0, T3, T6 but not at T60. According to the Renal Risk Score, patients were classified as Low (n = 8), Medium (n = 47) and High (n = 39) risk, and showed significant differences in both eGFR levels, proportion of hemodialysis, at T0, T3, T6 and end-stage kidney disease (ESKD) at T60. Even patients classified as Mixed (Berden) and as Medium or High risk (Renal Risk Score) had significant improvement from T0 to T6. Relapse could not be predicted by either system. Both methods were able to predict short-term renal function outcome and need for hemodialysis, but the Renal Risk Score showed significant superiority in predicting renal function outcome and ESKD after long-term follow up.

Identification of inflammatory biomarkers in IgA nephropathy using the NanoString technology: a validation study in Caucasians

Objective and designImmunoglobulin A nephropathy (IgAN) is a kidney disease characterized by the accumulation of IgA deposits in the glomeruli of the kidney, leading to inflammation and damage to the kidney. The inflammatory markers involved in IgAN remain to be defined. Gene expression analysis platforms, such as the NanoString nCounter system, are promising screening and diagnostic tools, especially in oncology. Still, their role as a diagnostic and prognostic tool in IgAN remains scarce. In this study, we aimed to validate the use of NanoString technology to identify potential inflammatory biomarkers involved in the progression of IgAN.SubjectsA total of 30 patients with biopsy-proven IgAN and 7 cases of antineutrophil cytoplasmic antibody (ANCA)-associated pauci-immune glomerulonephritis were included for gene expression measurement. For the immunofluorescence validation experiments, a total of 6 IgAN patients and 3 controls were included.MethodsTotal RNA was extracted from formalin-fixed paraffin-embedded kidney biopsy specimens, and a customized 48-plex human gene CodeSet was used to study 29 genes implicated in different biological pathways. Comparisons in gene expression were made between IgAN and ANCA-associated pauci-immune glomerulonephritis patients to delineate an expression profile specific to IgAN. Gene expression was compared between patients with low and moderate risk of progression. Genes for which RNA expression was associated with disease progression were analyzed for protein expression by immunofluorescence and compared with controls.ResultsIgAN patients had a distinct gene expression profile with decreased expression in genes IL-6, INFG, and C1QB compared to ANCA patients. C3 and TNFRSF1B were identified as potential biomarkers for IgAN progression in patients early in their disease course. Protein expression for those 2 candidate genes was upregulated in IgAN patients compared to controls. Expression of genes implicated in fibrosis (PTEN, CASPASE 3, TGM2, TGFB1, IL2, and TNFRSF1B) was more pronounced in IgAN patients with severe fibrosis compared to those with none.ConclusionsOur findings validate our NanoString mRNA profiling by examining protein expression levels of two candidate genes, C3 and TNFRSF1B, in IgAN patients and controls. We also identified several upregulated mRNA transcripts implicated in the development of fibrosis that may be considered fibrotic markers within IgAN patients.

Early growth response 1 as a podocyte injury marker in human glomerular diseases.

In human glomerular diseases, visualizing podocyte injury is desirable since podocytes do not regenerate and podocyte injury leads to podocyte loss. Herein, we investigated the utility of immunostaining for early growth response 1 (EGR1), which is expressed in injured podocytes from the early stages of injury in animal experiments, as a podocyte injury marker in human glomerular diseases. This study included 102 patients with biopsy-proven glomerular diseases between 2018 and 2021. The proportion of EGR1 expression in podocytes (%EGR1pod) was analyzed in relation to clinical and histopathological features, including glomerular and urinary podocyte-specific markers. %EGR1pod correlated significantly with the urinary protein:creatinine ratio, urinary nephrin and podocin mRNA levels, and glomerular podocin staining (rho=0.361, 0.514, 0.487 and -0.417, respectively; adjusted P=.002, <.001, <.001 and <.001, respectively). Additionally, %EGR1pod correlated with cellular/fibrocellular crescents (rho=0.479, adjusted P<.001). %EGR1pod was high in patients with glomerulonephritis, such as immunoglobulin A nephropathy (IgAN), lupus nephritis and antineutrophil cytoplasmic antibody-associated glomerulonephritis, and in those with podocytopathies, such as membranous nephropathy and primary focal segmental glomerulosclerosis, while %EGR1pod was low in patients with minimal change disease. In a subgroup analysis of IgAN, %EGR1pod was higher in Oxford C1 patients than in C0 patients. However, unexpectedly, patients with higher %EGR1pod were more prone to attain proteinuria remission, suggesting that EGR1 in the context of IgAN reflects reversible early injury. Our findings indicate that EGR1 is a promising potential marker for identifying active early podocyte injury in human glomerular diseases.

Clinical Phenotype and Outcomes of Indo-Asian Patients with ANCA-Associated Glomerulonephritis in the North West, UK

ANCA-associated vasculitides (AAV) are rare, autoimmune conditions associated with end-stage kidney disease (ESKD) and mortality. Data have predominately been from White populations of European ancestry although geographical differences are well documented. Few studies have looked at the incidence, phenotype and clinical outcomes of ethnic minority patients, in particular Indo-Asian populations. A two-center, retrospective cohort study was conducted of patients with ANCA-associated glomerulonephritis (AAGN), self-identifying as Indo-Asian in the North West, UK between 2009 and 2023. A control group of White patients was identified from the same databases and recruited consecutively in relation to the original cohort of Indo-Asian patients. A total of 66 patients were included, 24 patients of Indo-Asian ethnicity and a control cohort of 42 patients of White ethnicity. Indo-Asian patients had a lower median age at diagnosis (53.0 vs. 57.5 years, p = 0.15) and there was an increased prevalence of diabetes mellitus (33.3% vs. 4.8%, p = 0.002) and a higher incidence of previous TB exposure (12.5% vs. 0%, p = 0.019). Outcomes including relapse, ESKD and mortality were similar. We demonstrated an increased crude incidence of AAGN in Indo-Asian patients in the UK compared to similar epidemiological studies. Consideration needs to be given to epidemiological and genetic research, achieved by collaboration and broader recruitment in clinical trials.

Complement alternative pathway determines disease susceptibility and severity in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis

Activation of the alternative pathway (AP) of complement is involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), although the underlying molecular mechanisms are unclear. To gain insight into the role of the AP, common gene variants in CFH/CFHR1-5, CFB, C3 and MCP, and longitudinal determinations of plasma C3, C4, FH, FHR-1, FHR-2, FHR-5, FB, properdin and sC5b-9 levels were analyzed in a Spanish AAV cohort consisting of 102 patients; 54 with active AAV (active cohort) and 48 in remission not receiving immunosuppressants or dialysis therapy (remission cohort). The validation cohort consisted of 100 patients with ANCA-associated glomerulonephritis. Here, we demonstrated that common genetic variants in complement components of the AP are associated with disease susceptibility (CFB32Q/W) or severity of kidney damage in AAV (CFH-H1, CFHH2 and ΔCFHR3/1). Plasma levels of complement components were significantly different between active and remission cohorts. In longitudinal observations, a high degree of AP activation at diagnosis was associated with worse disease outcome, while high basal FHR-1 levels and lower FH/FHR-1 ratios determined severe forms of kidney associated AAV. These genetic and plasmatic findings were confirmed in the validation cohort. Additionally, autoantibodies against FH and C3 convertase were identified in one and five active patients, respectively. Thus, our study identified key genetic and plasma components of the AP that determine disease susceptibility, prognosis, and severity in AAV. Our data also suggests that balance between FH and FHR-1 is critical and supports FHR-1 as a novel AP-specific therapeutic target in AAV.

Classical Monocyte-Derived and Lipid-Associated TREM2+ Macrophages Orchestrate Inflammatory and Fibrotic Processes in ANCA-Associated Glomerulonephritis

Classical Monocyte-Derived and Lipid-Associated TREM2+ Macrophages Orchestrate Inflammatory and Fibrotic Processes in ANCA-Associated Glomerulonephritis

Avacopan in Combination with Rituximab and Low-Dose Cyclophosphamide for Treatment of Severe ANCA-Associated Glomerulonephritis

Avacopan in Combination with Rituximab and Low-Dose Cyclophosphamide for Treatment of Severe ANCA-Associated Glomerulonephritis

A Case of Paraneoplastic ANCA-Associated Glomerulonephritis in a Patient with Non-Small-Cell Lung Carcinoma

A Case of Paraneoplastic ANCA-Associated Glomerulonephritis in a Patient with Non-Small-Cell Lung Carcinoma

Treatment, Relapse, and Complications of Myeloperoxidase (MPO) and PR3 ANCA-Associated Glomerulonephritis: Report from an Australian Centre

Treatment, Relapse, and Complications of Myeloperoxidase (MPO) and PR3 ANCA-Associated Glomerulonephritis: Report from an Australian Centre

Peripheral Neuropathy Leading to Diagnosis of ANCA-Associated Glomerulonephritis

Peripheral Neuropathy Leading to Diagnosis of ANCA-Associated Glomerulonephritis

Renal tubular and glomerular estrogen receptor ß levels are lower in lupus nephritis than in familial Mediterranean fever-associated renal amyloidosis.

Estrogen has been thought to play an essential role in the disease pathogenesis of systemic lupus erythematosus, which is 9-10 times more prevalent in the female population. It has been shown that irregular estrogen/estrogen receptor signaling pathways may contribute to the pathophysiology of various renal diseases. In this study, we compared renal estrogen receptors between lupus nephritis, familial Mediterranean fever-associated renal amyloidosis, ANCA-associated nephritis, and intact kidney to investigate their role in the pathophysiology of renal diseases. This study was designed as a retrospective cohort study. Thirty systemic lupus erythematosus patients with lupus nephritis, 12 familial Mediterranean fever amyloidosis and 10 ANCA-associated glomerulonephrites, and 14 individuals with normal renal histology were included in the study. Tubular estrogen receptor ß expression score was found to be significantly higher in the familial Mediterranean fever [5 (1-8)] group than in the lupus nephritis [0 (0-1)] (B = 1.385, OR = 3.996, CI %95 = 1.805-8.846, p = .001) and ANCA [4 (1-6.5)] (B = -1.431, OR = 0.239, CI 95% = 0.093-0.614, p = .003) groups. A significant correlation was found between serum creatinine values and tubular estrogen receptor ß expression score (OR = 0.565, CI 95% = 0.622-1.402, p < .0001). In ANCA-associated glomerulonephritis, a significant relationship was found between fibro cellular crescents in renal biopsy and glomerular estrogen receptor ß expression score (OR = 0.247, CI 95% = 0.11-0.999, p = .045) and tubular estrogen receptor ß expression score (OR = 0.282, CI 95% = -0.180-2.812, p = .026). This study showed that tubular estrogen receptor ß expression score was elevated in familial Mediterranean fever amyloidosis and correlated with serum creatinine levels and renal crescents.