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Objective: To explore the clinical characteristics of double-seropositive patients (DPPs) with anti-glomerular basement membrane (Anti-GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA)., Methods: We collected patients with both ANCA and anti-GBM positive glomerulonephritis who were hospitalized in the Department of Nephrology at the First Affiliated Hospital of Nanjing Medical University from January 2010 to August 2022. Retrospective analysis of the baseline clinical characteristics of patients and follow-up to explore relevant factors affecting renal and patient survival., Results: A total of 386 patients, including 69 ANCA negative anti-GBM glomerulonephritis patients, 296 anti-GBM negative ANCA associated vasculitis (AAV) patients, and 21 DPPs were enrolled in this study. Among the 21 DPPs aged 68.0 years (59.5, 74.0), there were 11 males and 10 females. The median serum creatinine at diagnosis was 629.0 (343.85, 788.75) μmol/L, and the median eGFR (CKD-EPI) was 7.58 (4.74, 13.77) mL/min. Fifteen cases (71.4 %) underwent initial RRT. After a follow-up of 40.0 (11.0, 73.0) months, 13 out of 21 DPPs (61.9 %) received maintenance RRT, while 49 out of 69 (71.0 %) ANCA negative anti-GBM-GN patients and 124 out of 296 (41.9 %) anti-GBM negative AAV patients received maintenance RRT (P < 0.001). Kaplan-Meier survival analysis showed that DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients (P = 0.001). Among the 21 patients with DPPs, renal survival was significantly better in patients with better initial renal function, including those who did not receive initial RRT (P = 0.003), with lower serum creatinine levels (Cr < 629.0 μmol/L, P = 0.004) and higher eGFR levels (eGFR ≥ 7.60 ml/min, P = 0.005) than those with poor initial renal function. At the end of follow-up, 14 out of 21 DPPs (66.7 %) survived. Survival analysis showed no significant difference among patients in DPPs group, ANCA negative anti-GBM-GN group, and anti-GBM negative AAV group., Conclusions: DPPs and ANCA negative anti-GBM-GN patients were more likely to progress to ESRD than anti-GBM negative AAV patients. In DPPs, the poor renal function at diagnosis might be a risk factor associated with poor renal survival., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Rapidly progressive glomerulonephritis caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is typically characterized as pauci-immune glomerulonephritis. However, immune complex (IC) deposition in the glomerulus has been reported in a growing number of studies. Here, we assess the presence of glomerular immune deposits alongside renal outcome in myeloperoxidase (MPO)-ANCA associated glomerulonephritis (MPO-ANCA GN)., Methods: Clinical and histopathologic characteristics of 97 patients with MPO-ANCA GN classified by renal biopsy from January 2008 to December 2019 were extracted retrospectively from electronic medical records. The extent of immune deposits in the kidney (C3, C4, C1q, IgA, IgG, IgM) at diagnosis were analyzed by immunofluorescence (IF). Patients were followed up for a median period of 15 months. The response to treatment and outcomes of renal and histological lesion changes were also assessed., Results: In our study, 41% (40/97) of patients showed positive IF (≥2+) for at least one of the six immunoglobulin or complement components tested. Patients with IC deposits showed higher levels of serum creatinine (p=0.025), lower platelet counts (p=0.009), lower serum complement C3 (sC3) (≤790 ml/L) (p=0.013) and serum IgG (p=0.018) than patients with pauci-immune (PI) deposition at diagnosis. End-stage renal disease was negatively associated with eGFR (HR 0.885, 95% CI 0.837 to 0.935, p<0.0001), platelet count (HR 0.996, 95% CI 0.992 to 1.000, p=0.046) and serum globulin (HR 0.905, 95% CI 0.854 to 0.959, p=0.001). Patients with lower sC3 levels showed a worse renal outcome than the patients with normal sC3 at diagnosis (p=0.003). Analysis of the components of the renal deposits found that patients with IgG deposits exhibited a poorer renal outcome compared to patients that were IgG negative (p=0.028). Moreover, Bowman's capsule rupture occurred less frequently in patients with IgM deposition compared with IgM negative counterparts (p=0.028). Vascular lesions and granuloma-like lesions had been seen more frequently in cases with IgA deposition than those without IgA deposition (p=0.03 and 0.015, respectively)., Conclusion: In conclusion, patients with immune complex deposits in the kidney showed less platelet count, lower sC3 and sIgG levels, and higher serum creatinine levels. Patients with low sC3 at initial and with continued low sC3 during the treatment displayed a trend toward poorer kidney survival. Moreover, the IC group showed a worse renal outcome than the PI group, further enforcing the present strategy of introducing complement targeted therapies in AAV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SH declared a shared affiliation with several of the authors, JO and PE, to the handling editor at the time of review., (Copyright © 2021 Lin, Shen, Zhong, Ooi, Eggenhuizen, Zhou, Luo, Huang, Chen, Wu, Meng, Xiao, Ao, Peng, Tang, Yin, Xiao, Zhou and Xiao.)

Objective: To determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN)., Methods: A total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed., Results: All 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups ( p < 0.001) and significantly lower in the sclerotic group ( p < 0.05). In addition, disease histopathologically classified as sclerotic ( p = 0.044), high serum creatinine level (≥320 μmol/L, p < 0.001), low albumin (<30 g/L, p = 0.024) and hemoglobin level (<90 g/L, p = 0.044) were associated with a greater risk of ESRD. After follow-up, 70 (62.5%) of 112 patients survived. Old age (≥60 years, p = 0.018) and low serum albumin (<30 g/L, p = 0.006) was significant risk factor for patient survival., Conclusion: Among patients with MPO-ANCA-GN, those with poor renal function, disease histopathologically classified as sclerotic, and lower albumin and hemoglobin levels were risk factors for ESRD, while older age and low serum albumin level were associated with a greater risk for all-cause mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ge, Yang, Yu, Sun, Zhang, Yuan, Zeng, Wang, Mao and Xing.)

Background: The aim of this study was to investigate the predictors of renal outcomes in crescentic and mixed class of ANCA-associated glomerulonephritis., Materials and Methods: We systematically reviewed the medical records of patients with ANCA-associated glomerulonephritis admitted to our hospital from December 2008 to December 2018, and found 30 patients with crescentic and 40 patients with mixed ANCA-associated glomerulonephritis., Results: End-stage renal disease developed in 33.3 and 25% patients over a median follow-up of 45.1 and 46.7 months in the crescentic and mixed group, respectively. There was no significant difference in renal survival rates between the two histological subgroups (log-rank p = 0.558). In the Cox regression model, old age, lower estimated glomerular filtration rate (eGFR), lower normal glomeruli ratio, and a higher tubular atrophy and interstitial fibrosis ratio were significantly associated end-stage renal disease (p < 0.05 for all). Among our patients, 17.1% were at low risk, 57.1% were at medium risk, and 25.7% were at high risk according to antineutrophil cytoplasmic antibody renal risk score and end-stage renal disease developed in 8.3, 40, and 66.7%, respectively (p = 0.024)., Conclusion: These findings indicated that the renal risk score was a better prognostic tool than Berden's classification in a cohort with crescentic and mixed histologic categories.

Introduction: This study aimed to investigate the clinical characteristics, risk factors, and outcomes of infection-related hospitalization (IRH) in patients with lupus nephritis (LN) and ANCA glomerulonephritis after intensive immunosuppressive therapy. Methods: Patients diagnosed with LN or ANCA glomerulonephritis who received intensive immunosuppressive therapy at the First Affiliated Hospital of Sun Yat-sen University from 2005 to 2014 were enrolled. Demographics, laboratory parameters, immunosuppressive agents, and IRH details were collected. Multivariable Cox regression was used, and hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. Results: Totally, 872 patients with 806 LN and 66 ANCA glomerulonephritis were enrolled, and 304 (34.9%) patients with 433 episodes of IRH were recorded. ANCA glomerulonephritis patients were more vulnerable to IRH than LN patients (53.0% vs. 33.4%, p  = .001). Multivariable Cox regression analysis showed that ANCA glomerulonephritis (HR = 1.62, 95% CI: 1.06-2.49, p  = .027), diabetes (HR = 1.82, 95% CI: 1.03-3.22, p  = .039) and a higher initial dose of prednisone (HR = 1.01, 95% CI: 1.00-1.02, p  = .013) were associated with a higher likelihood of IRH. Higher albumin (HR = 0.96, 95% CI: 0.94-0.98, p  < .001), globulin (HR = 0.98, 95% CI: 0.96-0.99, p  = .008), and eGFR (HR = 0.99, 95% CI: 0.99-1.00, p  < .001), were associated with a lower likelihood of IRH. The rates of transfer to ICU and mortality for ANCA glomerulonephritis patients were higher than those for LN patients (22.9% vs. 1.9%, p  < .001, and 20.0% vs. 0.7%, p  < .001, respectively). Conclusions: ANCA glomerulonephritis patients had a higher risk of IRH and poorer outcome once infected after intensive immunosuppressive therapy than LN patients. More strict control for infection risks is required for ANCA glomerulonephritis patients who undergo intensive immunosuppressive therapy.

Background: Rapidly progressive glomerulonephritis (RPGN) has been known to have a poor prognosis. Although evidence across adult RPGN cases has accumulated over many years, the number of case series in adolescents and young adults has been limited, requiring further studies., Methods: A total of 1,766 cases from 1989 to 2007 were included in this nationwide questionnaire survey, led by Intractable (former name, Progressive) Renal Diseases Research, Research on intractable disease, from the Ministry of Health, Labour and Welfare of Japan. To elucidate age-related differences in 2-year patient and renal survival rates, the cases were divided into the following four groups: children (0-18 years), young adults (19-39 years), the middle-aged (40-64 years), and the elderly (over 65 years)., Results: Of the 1,766 total RPGN cases, antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis comprised 1,128 cases (63.9% of all RPGN cases), showing a tendency to increase with age. Two-year patient survival for RPGN was 93.9% among children, 92.6% in young adults, 83.2% in the middle-aged, and 68.8% in the elderly. The younger group (children plus young adults) showed a clearly higher survival rate compared to the older group (middle-aged plus elderly) (p<0.05). ANCA-associated glomerulonephritis also showed similar age-related results with all RPGN cases. The comparison of renal prognosis showed no statistically significant differences both in RPGN and in ANCA-associated GN., Conclusion: The present study described the age-dependent characteristics of the classification of RPGN, especially focusing on a better prognosis of the younger group in patient survival both in RPGN and in ANCA-associated GN., Competing Interests: The authors have declared that no competing interests exist.

Background: True population-based clinical and outcomes data are lacking for anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Therefore we aimed to estimate the incidence, prevalence and mortality of AAGN, as well as the relationship between the grade of chronic renal damage at presentation and renal and non-renal outcomes., Methods: Patients with AAGN were identified among a population-based incident cohort of 57 Olmsted County residents diagnosed with ANCA-associated vasculitis (AAV) in 1996-2015. Incidence rates were age and sex adjusted to the 2010 US white population. Age- and sex-adjusted prevalence was calculated for 1 January 2015. Survival rates were compared with expected rates in the Minnesota population. Chronic renal damage was assessed by chronicity score (CS) on biopsies performed at diagnosis., Results: Thirty-four (60%) patients had AAGN. Of these, 65% had microscopic polyangiitis (MPA) and 74% were myeloperoxidase (MPO)-ANCA positive. The annual incidence of AAGN was 2.0/100 000 population [95% confidence interval (CI) 1.3-2.7] and the overall prevalence was 35/100 000 (95% CI 24-47). Mortality for AAGN was increased (P < 0.001), whereas mortality for AAV without glomerulonephritis did not differ from the general population. Minimal to mild CS predicted recovery of renal function at 1 year; clinical diagnosis (granulomatosis with polyangiitis versus MPA) and ANCA specificity (proteinase 3 versus MPO) did not. This observation was replicated in an independent cohort of 38 newly diagnosed AAGN patients seen at our centre over the 1999-2014 period., Conclusions: The annual incidence and prevalence of AAGN in Minnesota are 2.0/100 000 and 35/100 000, respectively. Mortality is worse compared with AAV patients without glomerulonephritis. More advanced renal damage at diagnosis predicts less renal recovery., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

As the population worldwide ages, the epidemic of kidney disease will also increase. Anti-neutrophil cytoplasmic antibodies (ANCA) positive rapidly progressive positive glomerulonephritis (RPGN) is the most common etiology for biopsied patients among the very elderly. Its pathological features and clinical course are well described, though there is still debate about the mechanism of injury involved in individual patients. From very ancient times, the cornerstone of treatment historically has been high-dose cyclophosphamide and a lengthy course of high-dose corticosteroids. Although this regimen has diminished the immediate mortality rate of RPGN, its intermediate and long-term adverse effects are not insignificant. Attempts to minimize toxicity and improve efficacy have been made through the years to allow physicians some options for therapy. Lower cumulative cyclophosphamide regimens, shorter corticosteroid courses, and the introduction of rituximab have modified the armamentarium for treatment of ANCA positive RPGN. As progress is made in understanding the molecular pathogenesis of this disease, new targets will be found for potential therapeutic attack. The complement system is an area of active interest for all glomerular diseases at this time. Indeed, animal studies and preliminary human studies suggest that targeting the complement system can ameliorate the course of ANCA-positive RPGN. Hopefully, as the population ages, we will see more and safer therapeutic options to treat this once rapidly fatal disease., (© 2018 S. Karger AG, Basel.)

Background: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited., Methods: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival., Results: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15-34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9-19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17-82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043)., Conclusions: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN., (© 2018 S. Karger AG, Basel.)

Aim: Pauci-immune extracapillary glomerulonephritis (PEGN) is one of the most common causes of rapidly progressive glomerulonephritis and is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). However, a significant number of individuals with PEGN test negative for ANCA and this study aimed to analyze the characteristics of this subgroup of patients., Methods: Patients from two centres who were diagnosed with PEGN between 1997 and 2014 were studied retrospectively. Clinicopathological characteristics and renal outcome were compared between patients presenting with pauci-immune necrotizing extracapillary glomerulonephritis associated or not with the presence of circulating ANCA., Results: Among the 114 patients with PEGN, 29 (25.4%) were ANCA negative. Compared with the 85 ANCA-positive patients, ANCA-negative patients were younger at the onset (54.8 ± 17.2 vs. 62 ± 14.0 years; P < 0.05). The median level of urinary protein excretion was significantly higher among ANCA-negative patients (3.1 vs. 1 g/24 h; P < 0.001), whereas no differences were found in renal function and need for dialysis between ANCA-negative and positive groups. Extrarenal involvement was present independently of ANCA status. Histological analysis showed that ANCA-negative patients were more likely to have mesangial proliferation (P < 0.05). Renal and global survival were similar between ANCA-negative and positive patients, and treatment response and relapse rates were comparable in both groups., Conclusions: ANCA-negative pauci-immune extracapillary glomerulonephritis is not a rare condition and is part of a systemic vasculitis disease. Although ANCA-negative patients have renal and histological characteristics that differ from ANCA-positive patients, renal survival and treatment response in PEGN are independent of ANCA status., (© 2015 Asian Pacific Society of Nephrology.)

Background: Outcome in patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated glomerulonephritis (AGN) is difficult to predict. Scoring of renal biopsies has significant but limited predictive value. We investigated whether analysis of plasma and urine levels, and immunostaining of biopsies for the pro-fibrotic peptide connective tissue growth factor (CTGF), might improve prediction of renal outcome., Methods: ANCA-positive patients were included. Renal biopsies were classified according to the AGN classification. Biopsies were stained for CTGF protein. CTGF was measured by ELISA at the time of renal biopsy in plasma and urine, and during follow-up in plasma., Results: Eighty-two patients were included. CTGF staining was positive in crescentic lesions. Plasma CTGF at the time of renal biopsy was 2.4 ± 1.7 pmol/mL when compared with 0.5 ± 0.0 pmol/mL in healthy controls (P < 0.01). Plasma CTGF was associated with cellular crescents, but not when corrected for renal function. Plasma CTGF at baseline was associated with fibrous crescents in the follow-up biopsy, also after correction for renal function. Plasma CTGF at baseline predicted renal survival more accurately than the AGN classification., Conclusion: In AGN patients, CTGF was overexpressed in crescentic glomeruli. Baseline plasma CTGF predicted the percentage of fibrous crescents in later biopsies, and renal survival, suggesting that CTGF is involved in the cicatrization, as opposed to resolution of cellular crescents in AGN., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Anti-neutrophil cytoplasm antibody (ANCA) associated vasculitis with renal involvement requires treatment with potentially toxic drugs to reduce morbidity and mortality, and there is a major challenge to determine clinical and histological features predictive of renal prognosis. The aim of our study was to evaluate the use of the 2010 international histological classification for ANCA-associated glomerulonephritis (AAGN) as a predictor of renal outcome when used in conjunction with other prognostic factors., Methods: One hundred and four patients with AAGN treated at our centre were included: 23 were classified as focal, 26 as crescentic, 48 as mixed and 7 as sclerotic. Renal outcomes were based on estimated glomerular filtration rate (eGFR) at 1 and 5 years, and on renal survival., Results: By univariate analysis, patients in the focal class had the best renal outcome, those in the sclerotic class the worst outcome, and those in the mixed and crescentic classes had intermediate renal survival. There was no significant difference in outcome between the mixed and crescentic classes. In multivariate models, histological class did not improve model fit or associate with renal outcome after adjusting for established prognostic factors. Lower percentage of normal glomeruli, greater degree of tubular atrophy (TA), MPO-ANCA positivity, increasing age and lower starting eGFR, all correlated with poorer renal outcomes., Conclusions: We conclude that, in our cohort of patients, the international histological classification is predictive of renal outcome in AAGN, but did not appear to be additionally informative over other established prognostic factors in multivariate analysis. However, it may be of value to combine the current histological classification with other established parameters, such as TA and percentage normal glomeruli., (© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Rapidly progressive renal failure is a common but severe feature of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A histopathological classification for ANCA-associated pauci-immune glomerulonephritis was developed for prognostication of these patients. The present study aims to classify patients of pauci-immune glomerulonephritis according to this classification and its impact on outcome. Eighty-six subjects with pauci-immune glomerulonephritis between July 2006 and October 2012 were included in the study. Their renal biopsies were reviewed and classified into focal, crescentic, sclerotic and mixed class as per the new classification. The outcomes were analyzed after 6 months of treatment. Of the 86 subjects, 34 (39.53 %) were granulomatosis with polyangiitis, 36 (41.86 %) microscopic polyangiitis, 1 eosinophilic granulomatosis with polyangiitis, while the rest (17.44 %) were unclassifiable. Thirteen (15.5 %), 43 (51.2 %), 12 (14.3 %) and 16 (19 %) patients were classified as focal, crescentic, sclerotic and mixed class, respectively. The mean serum creatinine at baseline was 280.23, 659.46, 573.72 and 542.78 µmol/L in focal, crescentic, sclerotic and mixed class, respectively. The probability of improvement in renal functions at 6 months decreased from focal to crescentic to mixed to sclerotic class, while the probability of death was highest in the sclerotic class followed by the mixed class. This difference in outcome was maintained irrespective of the clinical diagnosis or the Birmingham Vasculitis Activity Score. Our study has shown that the histopathological classification can be used to predict the severity of renal dysfunction as well as the treatment outcomes in pauci-immune glomerulonephritis.

Background and Objectives: A proposed histopathologic classification for ANCA-associated GN is predictive of long-term renal outcome in adult populations. This study sought to validate this system in a pediatric cohort., Design, Setting, Participants, & Measurements: This was a retrospective, single-center, cohort study of 40 children diagnosed and followed until their transition to adult care at one institution between 1987 and 2012. Renal biopsy specimens were reviewed by a pathologist blinded to patient outcome and were classified using the new histopathologic classification system of focal, crescentic, mixed, and sclerotic groups. Time to the composite outcome of CKD stages 3 and 4 (determined by eGFR with repeated creatinine measures using the Schwartz equation) or ESRD (defined as dialysis dependence or transplantation) were ascertained., Results: The study population consisted of 40 children (70% female), followed for a median of 2.4 years. The biopsy specimens were categorized as focal in 13 patients (32.5%), crescentic in 20 (50%), mixed in two (5%), and sclerotic in five (12.5%). Mixed and crescentic were combined for analyses. Survival analysis of time to the composite renal endpoint of at least 3 months of eGFR<60 ml/min per 1.73 m(2) or ESRD differed significantly among the three biopsy groups log-rank P<0.001), with an adjusted hazard ratio of 3.14 (95% confidence interval, 0.68 to 14.4) in the crescentic/mixed group and 23.6 (95% confidence interval, 3.9 to 144.2) in the sclerotic category compared with the focal category. The probability of having an eGFR>60 ml/min per 1.73 m(2) at 2 years was 100% for the focal, 56.5% for the crescentic/mixed, and 0% for the sclerotic biopsy categories., Conclusions: This study showed the clinical utility of this histopathologic classification system and its ability to discriminate renal outcomes among children with ANCA GN., (Copyright © 2014 by the American Society of Nephrology.)

Objective: Anti-myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)- related nephritis constitutes 60% of rapidly progressive glomerulonephritis (RPGN) in Japan. The reported 1-year survival rate is over 80%, however, the long-term prognosis remains unknown. We therefore investigated the prognosis and factors affecting the clinical course of patients., Methods: We retrospectively investigated 74 patients (female, n=42; median age, 73.0 years) with MPO-ANCA-related nephritis. The patients were admitted to Fukushima Medical University and two affiliated hospitals between 2000 and 2010., Results: Median estimated GFR (eGFR) was 12.1 mL/min/1.73 m2 at admission. The Birmingham Vasculitis Activity Score (BVAS version 3: max 63 points) at diagnosis and at 4 weeks after start of treatment were 15.0 and 5.0, respectively. Twenty-three patients (31%) died during a median observation period of 30.5 months. Sixteen patients (22%) presented with end-stage renal disease (ESRD) at the initial phase, and needed regular dialysis therapy. Multivariate Cox proportional hazards model analysis revealed that renal death at the initial phase was a significant risk factor for all-cause death (Hazard ratio, 5.72; 95% confidence interval, 2.49-13.09; p<0.001). Furthermore, BVAS>6, evaluated 4 weeks after start of treatment, is an independent risk factor for ESRD and patient survival., Conclusion: This is the first investigation to demonstrate clinical features focusing on MPO-ANCA-related nephritis. Renal death at the initial phase of treatment is a powerful risk factor for all-cause death in patients with MPO-ANCA-related nephritis. Patients at high risk of death and ESRD could be stratified according to BVAS.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune glomerulonephritis (GN) is the most common finding in very elderly patients biopsied for acute kidney injury. Appropriate treatment strategies in this age group are currently undefined since it is unclear whether the benefits of immunosuppression exceed the risks. We retrospectively evaluated a cohort of 78 cases of biopsy-proven pauci-immune GN in individuals aged >80 years of whom 72% were p-ANCA and 20% were c-ANCA positive. The patients treated with immunosuppression had a significantly lower incidence of end-stage renal disease (ESRD) 1 year after biopsy (36%) compared with untreated patients (73%; P=0.03). Only peak serum creatinine before biopsy and the use of immunosuppression influenced progression to ESRD. There was no significant difference in the 1-year mortality rates between these groups (46 vs 64%; P=0.3). However, when follow-up was extended beyond 2 years, immunosuppression was associated with a lower risk of death (HR 0.33, 95% CI 0.11-0.97) and death or ESRD (HR 0.16, 95% CI 0.06-0.42) in multivariable models.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are predominantly diseases of older patients, frequently involving the kidney. Bomback and colleagues studied disease outcome in very elderly patients (>80 years old) with ANCA-associated renal disease. Immunosuppression resulted in lower rates of end-stage renal disease at 1 year and lower mortality at 2 years. Although these data suggest we should treat these elderly patients with immunosuppression, the criteria for patient selection and the dosage and duration of the treatment regimen need to be established.

Background and Objectives: Lupus nephritis is a classic immune complex glomerulonephritis. In contrast, antineutrophil cytoplasmic antibodies are associated with necrotizing and crescentic glomerulonephritis, in the absence of significant immune deposits. Antineutrophil cytoplasmic antibodies are detected by indirect immunofluorescence in 20% of patients with systemic lupus erythematosus. We report 10 cases of necrotizing and crescentic lupus nephritis with antineutrophil cytoplasmic antibody seropositivity., Design, Setting, Participants, & Measurements: Ten patients with systemic lupus erythematosus, antineutrophil cytoplasmic antibody positivity, and renal biopsy findings of lupus nephritis and antineutrophil cytoplasmic antibody-associated glomerulonephritis were identified. The clinical features, pathologic findings, and outcomes are described., Results: The cohort consisted of eight women and two men with a mean age of 48.4 yr. Perinuclear antineutrophil cytoplasmic antibody was detected by indirect immunofluorescence in nine patients. Four of the nine patients and the single remaining patient were found to have myeloperoxidase-antineutrophil cytoplasmic antibodies by enzyme-linked immunosorbent assay. Clinical presentation included proteinuria, hematuria, and acute renal insufficiency, with mean creatinine of 7.1 mg/dl. All biopsies exhibited prominent necrosis and crescents with absent or rare subendothelial deposits and were interpreted as lupus nephritis and antineutrophil cytoplasmic antibody-associated glomerulonephritis. All patients received cyclophosphamide and prednisone. Three patients died of infectious complications. Among the remaining seven patients, five achieved a complete or near-complete remission, one had a remission with subsequent relapse, and one had no response to therapy., Conclusion: Antineutrophil cytoplasmic antibody-associated necrotizing and crescentic glomerulonephritis may occur superimposed on lupus nephritis. In patients with lupus nephritis and biopsy findings of prominent necrosis and crescent formation in the absence of significant endocapillary proliferation or subendothelial deposits, antineutrophil cytoplasmic antibody testing by enzyme-linked immunosorbent assay is recommended.

In patients who have anti-neutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis and are on dialysis at time of diagnosis, renal function is sometimes insufficiently restored by immunosuppressive treatment, which often coincides with potentially lethal adverse effects. This study investigated the clinical and histologic variables that determine the chances of dialysis independence, dialysis dependence, or death after 12 mo in these patients. Sixty-nine patients who had ANCA-associated glomerulonephritis and were dialysis dependent at diagnosis received uniform, standard immunosuppressive therapy plus either intravenous methylprednisolone or plasma exchange. Eleven clinical and histologic variables were assessed. Univariate and binary logistic regression analyses were performed. Predictive parameters were entered into a two-step binary logistic regression analysis to differentiate among the outcomes of dialysis independence, dialysis dependence, or death. The point at which the chance of therapy-related death exceeded the chance of dialysis independence was determined. The chance of recovery exceeded the chance of dying in most cases. Intravenous methylprednisolone as adjunctive therapy plus <18% normal glomeruli and severe tubular atrophy increased the chance of therapy-related death over the chance of dialysis independence. Plasma exchange treatment plus severe tubular atrophy and <2% normal glomeruli increased the chance of therapy-related death over that of dialysis independence. Even with ominous histologic findings, the chance of renal recovery exceeds the chance of therapy-related death when these patients are treated with plasma exchange as adjunctive therapy.

Background: Renal function at diagnosis is a strong predictor not only of renal survival but also of patient survival of those with anti-neutrophil cytoplasmic antibody (ANCA)-associated small vessel vasculitis (ASVV). Apart from the renal function at diagnosis, there are no other established risk factors for renal outcome in ASVV. We have previously reported that in other forms of glomerular diseases, an increased urine excretion of IgM is an early marker of poor renal outcome., Methods: In this single-centre observational study, the prognostic significance of urine IgM excretion and other selected prognostic markers was studied in 83 consecutive patients (49 males, 34 females) with ASVV with renal involvement., Results: Patient survival at 1 and 5 years was 93 and 77%, respectively, and the corresponding figures for renal survival censored for death were 84 and 76%. Univariate analysis indicated that patient survival was inversely associated with age, male sex, serum creatinine, low serum albumin and high urine IgM excretion. Renal survival was inversely associated with serum creatinine, albuminuria and urine IgM. Multivariate analysis determined that only old age and high urine IgM excretion were independent predictors of patient survival [odds ratio (OR) = 11.2 and 4.4, respectively, P<0.01]. Urine excretion of IgM was the only independent predictor of end-stage renal disease (OR = 19.8, P = 0.004). Overall, 35% of the patients reached the composite end-point of either death or renal replacement therapy. Urine IgM excretion was the most potent single predictor of such an outcome (OR = 7.7, P = 0.000)., Conclusion: The occurrence of an increased amount of IgM in urine at presentation is a strong marker of poor prognosis for patients with ANCA-associated renal vasculitis.

A national survey concerning rapidly progressive glomerulonephritis (RPGN) was conducted in Japan between 1989 and 2000 and resulted in the registration of 715 patients with RPGN. Among the documented patients, the most frequent primary disease was primary pauci-immune crescentic glomerulonephritis (n = 283), and the second most frequent was microscopic polyangitis (n = 127). Overall, 370 patients had MPO-ANCA, and 23 patients had PR3-ANCA. We found that both renal and patient survivals were significantly worse in patients with MPO-ANCA-associated RPGN than patients with PR3-ANCA. Fifty-three patients received apheresis therapy with various combinations of immunosuppressive regimens. They had higher serum creatinine, higher CRP, and a higher frequency of complicated pulmonary involvements as compared to the controls without apheresis therapy. In dialysis-dependent patients, no additional benefit from apheresis therapy was observed. Only pulmonary renal syndrome patients with CRP > 6 mg/dl at presentation showed a slightly better prognosis (patient survival with apheresis; 66.7%, without apheresis; 56.7%). Furthermore, a rapid MPO-ANCA titer reduction was observed in patients treated with apheresis. Patients with MPO-ANCA-associated RPGN were older, and had more chronic and sclerotic lesions than patients with PR3-ANCA-associated RPGN. Based on these findings, we suggest that a lower dose of immunosuppressant should be considered in order to avoid opportunistic infection. In this situation, cytapheresis is the treatment of choice. Nevertheless, in patients with an aggressive form of RPGN with rapid deterioration of renal function like the PR3-ANCA-associated RPGN, or pulmonary renal syndrome complicated severe inflammation, or relapses with high MPO-ANCA titer, we conclude that apheresis therapy should be considered., ((c) 2005 Wiley-Liss, Inc.)

Background: In a substantial proportion of patients with crescentic glomerulonephritis (CGN), both anti-glomerular basement membrane (GBM) antibodies and antineutrophil cytoplasmic antibodies (ANCAs) with specificity for myeloperoxidase (MPO-ANCA) are detected. In the present study, we questioned whether histological and clinical features of patients with both ANCA and anti-GBM antibodies differ from those of patients with either ANCA or anti-GBM alone., Methods: We reviewed the Limburg renal biopsy registry (1978 to 2003; n = 1,373) for cases of CGN. The presence of linear fluorescence on renal biopsy and the presence of ANCA and/or anti-GBM antibodies were measured. Subsequently, we assessed patient characteristics and follow-up and compared histological findings among the different groups., Results: We identified 46 MPO-ANCA-positive, 10 double-positive, and 13 anti-GBM-positive patients. Mean ages were 63, 64, and 52 years (P = 0.04), and serum creatinine levels were 5.0, 10.3, and 9.6 mg/dL (445, 910, and 850 micromol/L), respectively (P = 0.01). Granulomatous periglomerular inflammation was found in either MPO-ANCA- or double-positive patients, but not in anti-GBM-positive patients with CGN without MPO-ANCAs. Patient survival among the 3 groups was different, although not statistically significant (log rank P = 0.17, with 75%, 79%, and 100% alive at 1 year, respectively). Renal survival analysis showed significant differences among the 3 groups (P = 0.04, with 65%, 10%, and 15% off dialysis therapy at 1 year, respectively)., Conclusion: In patients with both anti-GBM antibodies and MPO-ANCAs, histological findings differ from those of patients with anti-GBM antibodies only. However, renal survival in these patients is not better than that in anti-GBM-positive patients and is worse compared with patients with MPO-ANCAs only.

Current treatment based on the use of cyclophosphamide and corticosteroids has changed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides from highly fatal into more chronic relapsing diseases. Relapses are a major problem in these diseases and cause increased morbidity and mortality. Current clinical research mainly focuses on achieving control of active disease while minimizing treatment-related toxicity. Risks for longterm relapse and their sequelae have been less thoroughly studied. It is noteworthy that, besides treatment, several other factors have been associated with the occurrence of relapses. Thus, compared to MPO-ANCA positive patients, patients with PR3-ANCA associated vasculitis run a significantly increased risk of experiencing relapses. ANCA-status during follow-up, levels of T cell activation, genetic background, and infectious and other exogenous factors have been linked to relapse as well. With a few exceptions, these associations are merely descriptive and not pathophysiologically proven. Furthermore, data on adapting treatment in accordance with risk factors for relapse are scarce. We review here the risk factors for relapse in ANCA-associated vasculitis, their potential pathogenic implications, and their possible role in preventive strategies and adaptations of current treatment policies.

Background: The purpose of the present study was to determine clinical prognostic factors on renal survival in 37 older patients with antineutrophil cytoplasmic autoantibody-associated pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated GN) who underwent renal biopsy at our Department between January 1996 and December 2000., Methods: The date of renal biopsy was used as the start date for entry into the study. Age, gender, 24 h proteinuria, serum creatinine level, blood pressure and ANCA were evaluated. The end-point for renal survival analysis was the start of chronic dialysis., Results: Twenty-six (70%) patients showed varying degrees of renal insufficiency, nine (24%) patients required dialysis, 13 (35%) were hypertensive (BP > or =140/90 mmHg) and 33 (89%) had proteinuria. During follow-up (31.73+/-17.39 months), 16% of the patients (6/37) developed end-stage renal disease (ESRD). The actuarial renal survival rate for all patients was 92% at 1 year and 76% at 3 years, for Wegener's granulomatosis 80% at 1 and 3 years, for microscopic polyangiitis 85% at 1 and 3 years, and for renal limited disease (GN) 75% at 1 and 37% at 3 years. Age (P = 0.024), arterial hypertension (P = 0.018), proteinuria (P = 0.037) and serum cre-atinine > or =400 micro mol/l (P = 0.047) were the most important risk factors for ESRD., Conclusion: The actuarial renal survival rate in elderly patients with ANCA-associated GN was 92% at 1 year and 76% at 3 years. Older age, arterial hypertension, proteinuria and serum creatinine > or =400 micro mol/l related to ESRD.

Background: The predictive value of clinical and renal histological features for renal outcome in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis was investigated in a prospective analysis of 96 patients with ANCA-associated vasculitis, and moderate renal involvement (creatinine <500 micromol/L)., Methods: The extent of 39 histological features in 96 biopsies (performed at entry in a clinical trial) was scored by two independent observers, according to a standardized protocol. Age, gender, diagnosis, glomerular filtration rate at entry (GFR0), ANCA-specificity, proteinuria, and treatment of these 96 patients were also taken into account. Treatment was standardized and started after the biopsy was performed. End-points included renal function at 18 months (GFR18), GFR18 corrected for GFR0 (CORGFR18), and the occurrence of relapse or death., Results: Parameters that most strongly correlated with GFR18 were GFR0 (r = 0.67), interstitial fibrosis (r = -0.45), glomerulosclerosis (r = -0.37), and tubular atrophy (r = -0.36). Parameters that most strongly correlated with CORGFR18 were segmental (r = 0.45) and cellular (r = 0.30) crescents, and fibrinoid necrosis (r = 0.46). None of the clinical and histological features predicted the occurrence of relapse or death. By applying a stepwise linear multiple regression analysis, we designed a formula for the estimation of renal function at 18 months: GFR18 (mL/min) = 17 + 0.71 x GFR0 (mL/min) + 0.34 x fibrinoid necrosis (%) + 0.33 x segmental crescents (%), (r2 = 0.60; standard deviation = 19 mL/min). Our results were independent of diagnosis, ANCA-specificity, and treatment limb., Conclusions: These data suggest that in ANCA-associated glomerulonephritis, GFR0 and predominantly chronic renal lesions are potent predictors of GFR18. Active lesions are associated with renal function recovery and may be reversible. The formula for the estimation of GFR18 shows that a combination of GFR0 and renal histology is a better predictor for GFR18 than GFR0 only.

As antineutrophil cytoplasmic antibody positive rapidly progressive glomerulonephritis (ANCA-RPGN) has a high risk of end stage renal failure and is a potentially life threatening disease, early aggressive therapy is recommended. However, aggressive immunosuppressive therapy may lead to immunodeficiency and subsequent mortality in the patients with this disease. Therefore, we need the index of immunodeficiency to cure the disease. To evaluate any risk factors, including therapies, on mortality in ANCA-RPGN, we conducted a retrospective investigation on patient survival in 32 patients with ANCA-RPGN by Kaplan-Meier analysis and the Cox regression model. Fourteen patients were treated with leucocytapheresis (LAP group) and the 18 patients were treated by steroid pulse therapy (steroid pulse group) as initial treatment. The patients were chosen for the different therapies at random. Two patients in the LAP group, and eight patients in the steroid pulse group had died within 6 months. The lymphocyte counts and CD4 cell counts after complete course of therapy were lower in the patients who died than in those who survived in the steroid pulse group. Patient survival was higher in the LAP group than in the steroid pulse group, but did not reach statistical significance. Multivariate Cox regression analysis showed that the factors influencing patient survival were initial serum creatinine, LAP therapy, CD4 cell counts, and lymphocytes at the end of treatment. Age, titer of MPO-ANCA, and percent of glomerular crescents were not found to have an effect on the patient survival. We recommend: that early diagnosis should be established, and immunosuppressive therapy may be done with monitoring of the lymphocyte and CD4 cell count., (Copyright 2002 S. Karger AG, Basel)

The purpose of this study was to determine the prognostic value of clinical, laboratory, and pathologic features at the time of presentation on patient and renal survival in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated microscopic polyangiitis and glomerulonephritis (excluding Wegener's granulomatosis). One hundred seven ANCA-positive patients with necrotizing and crescentic glomerulonephritis, including 69 with evidence for microscopic polyangiitis, were evaluated for this study. The relative risk of death was calculated for the following potential prognostic indicators: (1) ANCA pattern; (2) pulmonary hemorrhage at onset; (3) presence of extrarenal manifestations versus renal limited disease; and (4) treatment with corticosteroids and cyclophosphamide (intravenous or oral), compared with corticosteroids alone. Cox's proportional hazard model was used to assess the predictive value of the following variables on renal survival: (1) age; (2) race; (3) pulmonary symptoms at onset of disease; (4) renal pathology; (5) ANCA pattern; and (6) peak serum creatinine values obtained near the time of renal biopsy. Patients were followed prospectively for 2.5 yr (range, 5 days to 12 yr 2 months). There were 12 disease-related deaths and 46 patients who reached ESRD. The relative risk (and 95% confidence interval) of patient death was 8.65 (3.36, 22.2) times greater in patients who presented with pulmonary hemorrhage, and 3.78 (1.22, 11.70) times greater in patients with cytoplasmic ANCA compared to those with perinuclear ANCA. The relative risk of pulmonary hemorrhage was no different by ANCA pattern. The risk of death was 5.56 times lower in the cyclophosphamide-treated patients versus those treated with corticosteroids alone. The predictors of renal survival were entry serum creatinine value (P = 0.0002), race (African Americans having a worse outcome compared with Caucasians, P = 0.0008), and the presence of arterial sclerosis on kidney biopsy (P = 0.0076) when controlling for age, ANCA pattern, microscopic polyangiitis versus glomerulonephritis alone, and pulmonary involvement. Pathology indices such as glomerular necrosis, glomerular crescents, glomerular sclerosis, and interstitial sclerosis were not predictive of renal survival when controlling for entry serum creatinine value, race, and arterial sclerosis. However, in the subgroup of patients with a peak creatinine value of < or = 3.0 mg/dL (N = 29), increased interstitial sclerosis was a predictor of a poor renal outcome (P = 0.04).