ANCA-associated Disease Research Articles

The Role of the Microbiome in Connective-Tissue-Associated Interstitial Lung Disease and Pulmonary Vasculitis.

The microbiome can trigger and maintain immune-mediated diseases and is associated with the severity and prognosis of idiopathic pulmonary fibrosis, which is the prototype of interstitial lung diseases (ILDs). The latter can be a major cause of morbidity and mortality in patients with connective-tissue diseases (CTD). In the present review, we discuss the current evidence regarding microbiome in CTD-ILD and pulmonary vasculitis. In patients with rheumatoid arthritis (RA) the BAL microbiota is significantly less diverse and abundant, compared to healthy controls. These changes are associated with disease severity. In systemic sclerosis (SSc), gastrointestinal (GI)-dysbiosis is associated with ILD. Butyrate acid administration as a means of restoration of GI-microbiota has reduced the degree of lung fibrosis in animal models. Although related studies are scarce for SLE and Sjögren's syndrome, studies of the gut, oral and ocular microbiome provide insights into the pathogenesis of these diseases. In ANCA-associated vasculitis, disease severity and relapses have been associated with disturbed nasal mucosa microbiota, with immunosuppressive treatment restoring the microbiome changes. The results of these studies suggest however no causal relation. More studies of the lung microbiome in CTD-ILDs are urgently needed, to provide a better understanding of the pathogenesis of these diseases.

Proteinase 3 (PR3)-Antineutrophil Cytoplasmic Antibody in a Patient with Minimal Change Disease: An Unusual Finding

Antineutrophil cytoplasmic antibodies (ANCA) are useful as markers for systemic vasculitis. PR3-ANCA antibodies have been also identified in association with chronic inflammatory and infectious conditions, other autoimmune diseases, malignancy, and certain drugs. The association of PR3 and minimal change disease (MCD) without vasculitis is not an expected finding. We report a case of MCD with PR3-ANCA positive title and no histopathological findings of vasculitis. This reports to an 86-year-old Caucasian woman without relevant past medical history and a normal renal function one month before presentation with sudden-onset nephrotic syndrome and rapidly progressive renal failure. Renal ultrasound was normal. Autoimmune screening using enzyme-linked immunosorbent assay (ELISA) revealed PR3-ANCA high titers (238.7UQ). Renal biopsy did not show vasculitis or crescentic glomerulonephritis. The glomeruli were normal. Autoimmune, inflammatory, infectious and malignant diseases were excluded. MCD was assumed and she started prednisolone with clinical and analytical improvement. ANCA-associated glomerular disease can coexist with a variety of other glomerular diseases including membranous nephropathy, lupus nephritis, IgA nephropathy, and bacterial infection-related glomerulonephritis. This association could be an incidental finding, but there may be an association with MCD not previously reported. Our case emphasizes the importance of performing renal biopsies before embarking on a full-scale immunosuppression therapy based on ANCA title alone.

Clinical Characteristics and Outcomes of Severe ANCA-Associated Renal Disease in a Multiethnic Urban Population

Clinical Characteristics and Outcomes of Severe ANCA-Associated Renal Disease in a Multiethnic Urban Population

Bilateral Pulmonary Cavitation as Predominant Phenotype in ANCA-Associated Disease

A 48-year-old female ex-smoker (30 pack years) with a history of lymphocytic colitis presented to a rheumatologist due to bilateral ankle pain and finger stiffness. Based on clinical and laboratory findings, rheumatoid arthritis was diagnosed. The patient reported no respiratory symptoms and no weight loss, night sweats, or febrile episodes. However, prior to intended immunosuppressive pharmacotherapy, thoracic imaging was performed. This surprisingly revealed large cavities in both lungs (Figure). Thereupon, the patient was referred to our Department of Pulmonary Medicine.

Clinicopathological features of IgG4-related kidney disease .

To explore the clinicopathological features of IgG4-related kidney disease (IgG4-RKD) in Chinese patients. We retrospectively analyzed the clinicopathological features of 7 patients with IgG4-RKD and reviewed relevant literature. There were 7 patients (4 males and 3 females) aged 41-78 years (median age: 57.1 years), with a mean affliction of 2.6 organs per patient. All 7 patients had elevated serum IgG4 levels, and most of them had acute or chronic renal insufficiency. Two patients had positive myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), and another 2 patients had positive serum antinuclear antibodies (ANA). All 7 patients had tubulointerstitial nephritis (TIN) with IgG4+ plasma cell infiltration, 3 patients also had glomerular lesions, 2 patients had ANCA-associated glomerulonephritis (ANCA-GN), and the remaining patient had membranous nephropathy (MN). All these patients were treated with glucocorticoids, and 3 of them were given cyclophosphamide simultaneously. Six patients achieved remission and had improved renal function, while 1 patient was on maintenance dialysis. IgG4-RKD should be diagnosed by combining the clinical data and renal pathological changes, and it should be differentiated from a variety of diseases. Although ANCA-associated vasculitis (AAV) and IgG4-related disease are distinguishable in most cases, coexistence of ANCA-GN and IgG4-RKD should be considered in some special cases.

P0462HEMODIALYSIS PREDICTORS IN ANCA-ASSOCIATED VASCULITIS AND ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE

Abstract Background and Aims Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and anti-glomerular basement membrane (GBM) disease are autoimmune diseases frequently associated with poor renal outcomes namely hemodialysis. Therefore, the aim of this study was to identify predictors of renal replacement therapy (RRT) at six months in patients with ANCA-associated vasculitis and/or anti-glomerular basement membrane disease. Method We performed a single center observational, retrospective study in 40 patients with ANCA-associated vasculitis and/or anti-GBM disease diagnosed between January 2013 and June 2019. Clinical, analytical and histological variables were included as well as therapeutic regimens and outcomes. The primary endpoint was renal replacement therapy (RRT) at six months. Continuous variables were presented as means or medians, according to normality and categorical variables presented as frequencies. The comparison between subgroups of patients was performed using the Wilcoxon, Fisher exact test or t-test, chi-square test, according to normality. Univariate logistic regression model was fitted to identify variables associated with renal replacement therapy. STATA 14.2 statistical package was used and p <0.05 was considered statistically significant. Results We identified 40 patients, with a mean age of 69 years-old, 18 (45%) were male, 37 (95%) Caucasian. Twenty-seven (68%) had hypertension and 3 (8%) diabetes. The majority (33, 83%) presented with constitutional symptoms. Pulmonary manifestations were seen in 12 (30%) and gastrointestinal in 5 patients (12%). The other symptoms were rare. The mean systolic blood pressure was 140 mmHg and mean diastolic blood pressure 73 mmHg. The mean hemoglobin in hospital stay was 9,4g/dL, albumin 3.0 mg/dL, erythrocyte sedimentation rate 77mm/h, C3 1,11 UQ, C4 0,30 UQ, proteinuria 1,42 gr/24h, hematuria 279 erythrocytes, serum creatinine 3,4 mg/dL, eGFR 14 ml/min/m2, uric acid 7.1 mg/dL. The average ANCA MPO titles were 382 UQ/L, PR3 751UQ/L and GBM 883UQ/L. During hospital stay 11 patients (28%) needed dialysis. Renal biopsy showed interstitial fibrosis and tubular atrophy grade 0 in 5 patients (13%), grade 1 in 13(33%), grade 2 in 8 (20%) and grade 3 in 14 (35%). The majority had no vessel involvement 24 (60%). Acute tubular necrosis was absent in 13 (33%) patients, grade 1 in 9 (23%) and grade 2 in 18 (45%). Inflammatory infiltrate was present in 25 patients (63%). Regarding treatment, 38 (95%) of patients received pulse methylprednisolone and all prednisolone. Rituximab was administered to 15 (38%) patients and Cyclophosphamide to 14 (35%). Eighteen (45%) received azathioprine and 3 (8%) mycophenolate mofetil. Plasmapheresis was performed in 14 patients (35%). The average time from beginning of symptoms to treatment initiation was 119 days. The mean follow-up was 1094 days. At discharge the mean serum creatinine was 2,5 mg/dL, eGFR 23ml/min/m2 and none of the patients died. At six months, mean serum creatinine was 1.6 mg/dL, eGFR 31ml/min/m2 but 15 (38%) patients were dialysis-dependent. Two relapses occurred and 17 (43%) had infections during this period. Five (13%) patients died. At 12 months, mean serum creatinine was 2.0 mg/dL, eGFR 29 ml/min/m2 and (9) 23% patients were dialysis dependent. Six (30%) patients had infections and 5 (13%) died. In the end of follow up 13 (33%) patients had died. On univariate analysis, hemoglobin (OR 0.59 [0.36-0.95], p = 0.031), uric acid (OR 1.85 [1.12-3.05], p = 0.027), hematuria (OR 1.00 [1.00-1.00], p = 0.013), hemodialysis performed during 1st hospital stay (OR 22.9 [2.3-217.9], p = 0.006) and plasmapheresis ( OR 12.0 [2.4-61.0], p = 0.003) were associated with RRT at six months. Conclusion RRT in AAV and anti-GBM disease has decreased over the last decades with the use of immunosuppressive therapies. Clinical presentation and plasmapheresis seem the major predictors for RRT.

АНЦА-ассоциированные интерстициальные заболевания легких: актуальные вопросы диагностики и лечения

АНЦА-ассоциированные интерстициальные заболевания легких: актуальные вопросы диагностики и лечения

Distinction between MPO-ANCA and PR3-ANCA-associated glomerulonephritis in Chinese patients: a retrospective single-center study.

To retrospectively investigate the clinical and histological features and outcomes of ANCA-associated glomerulonephritis (AAGN) with different ANCA serotypes. A total of 467 AAGN patients were divided into MPO-AAGN (MPO) and PR3-AAGN (PR3) groups according to ANCA serotype. Clinical and histological features and renal outcomes were compared. In this study, 429 (91.9%) patients tested positive for MPO-ANCA, and 38 (8.1%) for PR3-ANCA. The median age at diagnosis (P = 0.017) and proportion of females (P = 0.003) were higher in the MPO group. Joint (P < 0.001), ENT (P = 0.000), skin (P = 0.007), and eye (P = 0.014) involvements were more common in the PR3 group. Compared with that in the PR3-group, a higher proportion of patients in the MPO group had microscopic polyangiitis (P = 0.000), and a lower proportion of exhibited granulomatosis with polyangiitis (P = 0.000). Patients in the MPO group also exhibited lower BVAS scores (P = 0.003) and higher serum albumin levels (P = 0.009). Histologically, a lower proportion of MPO patients had crescentic glomerulonephritis (P = 0.028) and acute tubule-interstitial lesion scores (P = 0.007), but a higher proportion of these patients exhibited mixed class glomerulonephritis (P = 0.032) than in the PR3 group. The relapse rate was lower (P = 0.020), and the 5-year relapse-free survival rate (P = 0.003) was higher in the MPO group than in the PR3 group. However, the 5-year renal survival rates (P = 0.106) were not significantly different. MPO-ANCA was predominant in Chinese patients with ANCA-associated vasculitis and renal disease. The epidemiological characteristics, extra-renal involvement, and histopathological classes and outcomes were different between MPO-positive and PR3-positive patients, implying that they might be two different disease entities.

Plasma exchange: exploring the complications and rationale for use

Plasma exchange is a tool used in the management of patients with ANCA-associated systematic vasculitis and Goodpasture's disease. The immune complex or protein is removed by plasma exchange and replacement fluid is used to maintain circulatory volume. The endpoint is disease control and, in conjunction with a variety of drugs, dialysis independence. This article discusses the rationale for treatment.

ANCA関連血管炎性中耳炎の2例

We report herein on two cases of ANCA-associated middle ear disease. Case 1: A 31-year-old female first complained of left earache and left aural obstruction with an increase in serum levels of PR3-ANCA. Case 2: A 78-year-old female first complained of bilateral ear discharge and hearing loss with an increase in serum level of MPO-ANCA. In both cases, we clinically suspected ANCA-associated middle ear disease and administered steroids and an immunosuppressant. In case 1, the patient was making steady progress as regards the local symptoms. In case 2, bilateral facial paralysis had developed two months after the start of the therapy. In neither case did aggravation of the general symptoms develop.In the treatment of ANCA-associated middle ear disease, we must follow up carefully long enough to prevent development of hearing loss and facial paralysis.

Genetically Determined Severity of Anti-Myeloperoxidase Glomerulonephritis

Myeloperoxidase (MPO) is a target antigen for antineutrophil cytoplasmic autoantibodies (ANCA). There is evidence that MPO-ANCA cause necrotizing and crescentic glomerulonephritis (NCGN) and vasculitis. NCGN severity varies among patients with ANCA disease, and genetic factors influence disease severity. The role of genetics in MPO-ANCA NCGN severity was investigated using 13 inbred mouse strains, F1 and F2 hybrids, bone marrow chimeras, and neutrophil function assays. Mouse strains include founders of the Collaborative Cross. Intravenous injection of anti-MPO IgG induced glomerular crescents in >60% of glomeruli in 129S6/SvEv and CAST/EiJ mice, but <1% in A/J, DBA/1J, DBA/2J, NOD/LtJ, and PWK/PhJ mice. C57BL6J, 129S1/SvImJ, LP/J, WSB/EiJ, NZO/HILtJ, and C3H mice had intermediate severity. High-density genotypes at 542,190 single nucleotide polymorphisms were used to identify candidate loci for disease severity by identifying genomic regions that are different between 129S6/SvEv and 129S1/SvImJ mice, which are genetically similar but phenotypically distinct. C57BL/6 × 129S6 F2 mice were genotyped at 76 SNPs to capture quantitative trait loci for disease severity. The absence of a dominant quantitative trait locus suggests that differences in severity are the result of multiple gene interactions. Invivo studies using bone marrow chimeric mice and invitro studies of neutrophil activation by anti-MPO IgG indicated that severity of NCGN is mediated by genetically determined differences in the function of neutrophils.

Renal medullary angiitis: a case series from a single institution

Renal medullary angiitis is a lesion involving the vasa recta of the medulla. The characteristic morphologic findings on renal biopsy include interstitial hemorrhage with associated polymorphonuclear leukocyte infiltration and karyorrhectic debris. A total of 18 cases have been described in three publications, all in the setting of antineutrophil cytoplasmic antibody (ANCA)-associated disease. We sought to detail the morphology and clinical significance of this lesion. A total of 38 cases of medullary angiitis were identified in our case files from January 2008 through August 2011. The clinical history was reviewed and pertinent information including patient age, gender, indication for biopsy, serum creatinine, and any positive serologic tests (ANCA) was collected for each biopsy. Cases with known and unknown ANCA status were reported separately. In total, 19 (63%) of 30 cases of medullary angiitis with known ANCA antibody status were ANCA positive, whereas 11 (37%) of 30 were determined to be secondary to other etiologies. The most common non-ANCA etiology of medullary angiitis was immunoglobulin A nephropathy (20%) followed by antibiotic treatment in the setting of infection. In ANCA-unknown cases, 4 (50%) of 8 had pauci-immune crescentic glomerulonephritis. No cases had renal cortex involvement. This is the largest study to date detailing the morphology of medullary angiitis and the first to show medullary angiitis outside the setting of ANCA-associated disease. It is an important lesion to recognize as it frequently suggests the presence of a systemic vasculitis and could be mistaken for interstitial nephritis.

Animal models of antineutrophil cytoplasm antibody-associated vasculitis

To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue. Rodent models of both myeloperoxidase (MPO) ANCA and proteinase 3 (PR3) ANCA associated vasculitis have been developed, which have provided important insights into the pathogenesis of ANCA-associated pulmonary and renal disease. The vast majority of in-vivo work in this field has concerned MPO-ANCA associated disease, although the last year has seen some advances in the modelling of anti-PR3 disease. As with all experimental animal models, they are flawed in one way or another by virtue of the means by which they are induced, but they have already provided novel directions for future intervention in these complex diseases. To date, there are no good models that replicate the granulomatous lesions found in granulomatosis with polyangiitis (GPA, formerly Wegener's) or the development of vasculitis lesions in organs other than the lungs or kidneys. ANCA-associated vasculitis can be induced in various forms in susceptible rodents. Further refinements are required for the full spectrum of disease phenotype to be replicated in animals, but critical new targets have been proposed based on the use of molecular blocking agents and transgenic animals to elucidate disease pathways.

Contaminated Cocaine and Antineutrophil Cytoplasmic Antibody-Associated Disease

Approximately 70% of illicit cocaine consumed in the United States is contaminated with levamisole. Most commonly used as a veterinary antihelminthic agent, levamisole is a known immunomodulating agent. Prolonged use in humans has been associated with cutaneous vasculitis and agranulocytosis. We describe the development of a systemic autoimmune disease associated with antineutrophil cytoplasmic antibodies (ANCA) in cocaine users. This complication appears to be linked to combined cocaine and levamisole exposure. Cases were identified between March 2009 and November 2010 at Massachusetts General Hospital's ANCA laboratory. Cocaine exposure was identified from patient history in all cases. Medical records were reviewed for clinical presentation and for laboratory and diagnostic evaluation. Thirty cases of ANCA positivity associated with cocaine ingestion were identified. All had antimyeloperoxidase antibodies and 50% also had antiproteinase 3 antibodies. Complete clinical and laboratory data were available for 18 patients. Arthralgia (83%) and skin lesions (61%) were the most frequent complaints at presentation. Seventy-two percent of patients reported constitutional symptoms, including fever, night sweats, weight loss, or malaise. Four patients had biopsy-proven vasculitis. Two cases of acute kidney injury and three cases of pulmonary hemorrhage occurred. From the entire cohort of 30, two cases were identified during the first 3 months of our study period and nine cases presented during the last 3 months. We describe an association between the ingestion of levamisole-contaminated cocaine and ANCA-associated systemic autoimmune disease. Our data suggest that this is a potentially life-threatening complication of cocaine use.

ANCA comes of age—but with caveats

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.

Recurrent ANCA-Associated Vasculitis After Renal Transplantation

Recurrent ANCA-Associated Vasculitis After Renal Transplantation

ANCA-associated vasculitides—lessons from the adult literature

Anti-neutrophil cytoplasmic antigen antibody (ANCA)-associated disease is a rare manifestation of primary systemic vasculitis in paediatric patients but one that carries significant morbidity, potential long-term disability and early mortality. It therefore requires a high index of suspicion, targeted investigation, prompt treatment and long-term follow-up with specialist input at every stage. The well-recognised diversity and overlap in clinical, laboratory and histopathological features of the ANCA-associated systemic vasculitides continue to hamper accurate diagnosis, confounding epidemiological data and necessitating a blanket approach to treatment, which is largely extrapolated from studies in adult patients and carries significant side-effects. Herein we summarise current knowledge of the epidemiology, pathogenesis, principal manifestations, investigation and evidence-based management, extrapolated from adult studies, of these disorders. We also discuss recent efforts towards classification of the childhood vasculitides that emphasise the value of histological diagnosis. Progress in our understanding of the pathophysiology underlying ANCA-associated disease should lead to targeted, safer and more effective therapies for these conditions. Nonetheless, many questions remain outstanding, and academic paediatricians face real challenges in identifying and collating the few cases they encounter into study cohorts. Meeting this challenge will require international collaboration, not only among paediatricians but also with the specialists taking over care of these patients as they reach adulthood.

Immune complex glomerulonephritis is induced in rats immunized with heterologous myeloperoxidase.

Anti-neutrophil cytoplasmic antibodies (ANCA), including anti-myeloperoxidase (MPO) antibodies, are associated with pauci-immune necrotizing small vessel vasculitis or glomerulonephritis. In order to substantiate a pathogenic role for ANCA, an animal model of pauci-immune ANCA-induced glomerulonephritis or vasculitis is required. Brouwer et al. reported pauci-immune glomerulonephritis in rats immunized with human MPO followed by perfusion of kidneys with lysosomal enzyme extract combined with H2O2, and suggested that this could serve as a model of ANCA-induced disease. We repeated these studies in spontaneously hypertensive rats (SHR) and Brown Norway rats (BNR). We immunized rats with human MPO. When circulating anti-MPO antibodies were detectable by indirect immunofluorescence microscopy and ELISA, blood pressure was measured, then perfusion of the left kidney of each rat was done via the renal artery in a closed, blood-free circuit with either MPO + H2O2, MPO, H2O2 alone or MPO + H2O2 + neutral protease. Rats were killed on day 4 or day 10 after perfusion, and specimens were examined by light and immunofluorescence microscopy. Pathological lesions and deposits of IgG, C3, and MPO were found in immunized rats perfused with MPO + H2O2 with or without neutral protease, or MPO alone, in both rat strains and on both day 4 and day 10. The degree of histologic injury was proportional in intensity to the amount of IgG immune deposits. Spontaneously hypertensive rats sustained more damage and higher blood pressure than Brown Norway rats. No lesion was observed in immunized rats perfused with H2O2 or in the non-perfused right kidneys. Some of the non-immunized rats perfused with MPO + H2O2 developed pathological lesions. In conclusion, these rat models are examples of immune complex-mediated glomerulonephritis, and therefore are not similar to human ANCA-associated disease.

Renal Expression of Adhesion Molecules in Anca-Associated Disease

Anti-neutrophil cytoplasmic autoantibodies (ANCA)-associated disease among other manifestations can underlie rapidly progressive glomerulonephritis (RPGN), with crescentic and necrotizing GN. Differences in pathogenic immune mechanisms in RPGN may provide differences in the renal expression of adhesion molecules mediating these lesions. Renal intercellular adhesion molecule 1 (ICAM-1; CD54) and vascular cell adhesion molecule 1 (VCAM-1; CD106) were assessed in 40 patients with type I RPGN (anti-glomerular basement membrane antibodies, n = 4), type II (immune complexes, n = 17), and type III (ANCA, n = 19). Enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G antibodies against the Goodpasture's antigen and indirect immunofluorescence and ELISA for myeloperoxidase (MPO) and proteinase 3 (PR3) were performed for ANCA testing. Ten normal renal tissues were used as controls. Relationships between ICAM-1 and VCAM-1, histopathologic features, and CD18, CD14, and CD3 cells were analyzed. Abnormal ICAM-1 and VCAM-1 in tubule was seen in >80% of biopsies with RPGN. Abnormal VCAM-1 in glomerular tuft was seen in >60% of biopsies with RPGN. Glomerular ICAM-1 was associated with less glomerulosclerosis (chi (2) = 6.719, p = 0.01), less interstitial fibrosis (chi (2) = 4.322, p < 0.05), and less tubular atrophy (chi (2) = 8.547, p < 0.005). Glomerular VCAM-1 was associated with glomerular leukocyte infiltration (chi (2) = 4.698, p < 0.05). Glomerular tuft stains of ++/+++ for VCAM-1 was observed in 10% from MPO-ANCA-GN patients but in 60% from PR3-ANCA-GN (Fi = 8.538, p = 0.03). The following conclusions can be made from this study. (1) The renal expression of ICAM-1 and VCAM-1 is upregulated in RPGN, and this is associated with the histological activity. (2) De novo expression of VCAM-1 on glomerular tuft suggests that endothelial cells play a role in RPGN. (3) De novo tubular expression of ICAM-1 and VCAM-1 suggests that epithelial cells may participate in adhesive interactions in RPGN. (4) De novo expression of VCAM-1 at the glomerular tuft in PR3-ANCA positive patients seems greater than in MPO-ANCA positive patients, which suggests that testing specific immune activation mechanisms may play a role in ANCA-associated GN.

Propylthiouracil-associated antineutrophil cytoplasmic antibody positive crescentic glomerulonephritis

The vasculitic syndromes of Wegeners granulomatosis, microscopic polyangitis, Churg-Strauss syndrome and renal limited variants are associated with antineutrophil cytoplasmic antibodies (ANCA). Positive ANCA are also seen in many viral infections, inflammatory bowel diseases and drugs. Drug-induced ANCA-associated renal disease is reported less frequently than drug-induced lupus nephritis. ANCA-positive crescentic glomerulonephritis due to propylthiouracil has been reported in children and adults especially in Japanese population. The renal outcome is better in propylthiouracil-associated ANCA-positive crescentic GN as compared with nondrug-induced crescentic GN. Propylthiouracil-associated ANCA-positive crescentic GN may or may not require steroid and cytotoxic therapy depending on the severity of renal failure. We report a case of propylthiouracil-associated ANCA-positive crescentic GN with severe renal failure; the renal function improved after steroid and cytotoxic therapy.