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Introduction Recent evidence suggests that complement activation is important in the pathogenesis of pauci-immune (PI) vasculitis. This is a retrospective investigation of the frequency of hypocomplementemia at pauci-immune glomerulonephritis (PIGN) diagnosis, in relation to vasculitic manifestations, renal histopathology, and treatment outcomes. Methods A total of 115 patients with biopsy-proven PIGN were categorized based on their serum complement C3 (sC3). Histopathology evaluation included activity and chronicity indexes. The primary outcome of interest was treatment resistance, defined as a progressive decline in kidney function, with persistently active urine sediment, leading to dialysis dependency or vasculitis-related death. Results In all, 20.9% of patients had low sC3 levels associated with more advanced renal impairment (P < 0.01), requiring acute dialysis (P < 0.01) more frequently compared to patients with normal sC3. Within 1 year, 85.7% of patients with normal sC3 responded to therapy, versus 58.3% of those with low sC3 (P = 0.001). The probability of treatment resistance was strongly associated with low sC3 (P = 0.004), high serum creatinine (P < 0.001), acute dialysis requirement (P < 0.001), and high histopathological score of chronicity (P < 0.01). Advanced histopathological activity was related to more intense interstitial leukocyte infiltration (P = 0.005) and higher likelihood of fibrinoid necrosis documentation in a vessel wall (P = 0.02). The probability of treatment resistance was higher in patients with low sC3 (odds ratio [OR] = 6.47, 95% confidence interval [CI] 1.47−28.35, P = 0.013), oliguria (OR = 29.57, 95% CI = 4.74−184, P < 0.0001), and high chronicity score (OR = 1.77, 95% CI = 1.23−2.54, P = 0.002). Conclusion Low sC3 is emerging as an independent predictor of treatment resistance in patients with PIGN associated with higher index of histopathological activity at diagnosis compared to normal sC3., Graphical abstract

Introduction: Crescents in glomeruli mean proliferation of parietal epithelium of Bowman's capsule with the presence of macrophages, lymphocytes, neutrophils, fibrin, and collagen. When crescents are present in >50% of nonfibrosed glomeruli, it is called crescentic glomerulonephritis (CGN). The presence of crescents is indicative of poorer prognosis. CGN can be pauci immune (PI), immune complex mediated (ICM), and anti-glomerular basement membrane (anti-GBM) disease. Aim: The aim was to study the clinicopathological spectrum of CGN over a period of 10 years in our center. Materials and Methods: Forty kidney biopsies with the presence of crescents over a period of 5 years were retrieved retrospectively from the histopathology records of the department of pathology. The clinical history, laboratory parameters, histopathology report, and the direct immunofluorescence (DIF) findings were analyzed. Results: Totally 40 cases had crescents on light microscopy. Out of these, 17 cases qualified for CGN. The mean age of the patients was 20 years. Nephritic syndrome was the most common presentation in these 17 cases. The mean creatinine level was 3.55 mg/dL. PI (7/17, 41.1%) was the most common category, followed by ICM (6/17, 35.2%) and anti-GBM (4/17, 23.5%). Out of the ICM, two cases were of IgA nephropathy with crescents and one of lupus with crescents. Conclusion: PI is the most common type of CGN. DIF examination is essential for exact categorization of CGN. Kidney biopsy in these cases can guide management and benefit patients with timely initiation of aggressive therapy.

One of the most common causes of rapidly progressive glomerulonephritis (RPGN) is pauci-immune crescentic glomerulonephritis (CrGN). In the majority of cases, this condition has a positive serologic marker, the anti-neutrophil cytoplasmic antibodies (ANCAs), but in approximately 10% there are no circulating ANCAs, and this subgroup has been known as the ANCA-negative pauci-immune CrGN. RPGN can be associated with systemic diseases, but there are only few case reports describing the association with mixed connective tissue disease (MCTD). The authors report a case of ANCA-negative CrGN associated with a MCTD.

Pauci-immune glomerulonephritis in the native kidney presents with renal insufficiency, proteinuria, and hematuria, and is usually due to anti-neutrophil cytoplasmic antibodies. Rarely, kidney transplants can show this pattern as de novo disease. We performed a retrospective analysis in 10 cases of de novo pauci-immune glomerulonephritis. The mean time from transplant to diagnostic biopsy was 32 months (range, 4-96). All biopsies showed focal necrotizing or crescentic glomerulonephritis (mean 16% glomeruli, range 2-36%). Immunofluorescence and electron microscopy showed a pauci-immune pattern. No patients had evidence of systemic vasculitis. Anti-neutrophil cytoplasmic antibody results were available for 7 patients and were negative in all but one. Most patients had functioning grafts at one year after diagnosis. Two patients had repeat biopsies that showed continued active glomerulonephritis. We report the first clinicopathologic series of de novo pauci-immune glomerulonephritis which appears to be a unique pathologic entity that may occur early or late post-transplant and in our cohort is not associated with systemic vasculitis and usually not associated with anti-neutrophil cytoplasmic antibodies. The degree of crescent formation and renal impairment are milder than those of pauci-immune crescentic glomerulonephritis in the native kidney.

We present a 61-year-old male with FLT3-mutated acute myeloid leukemia treated with midostaurin who developed acute kidney injury requiring hemodialysis and pulmonary renal syndrome. Antibodies to proteinase-3, myeloperoxidase, and glomerular basement membrane were negative. Renal biopsy confirmed acute pauci-immune focal necrotizing glomerulonephritis (GN) with fibrin crescents indicating rapidly progressing glomerulonephritis. He improved with pulse methylprednisolone, intravenous cyclophosphamide, and plasma exchange with resolution of hemoptysis. This case highlights the importance of prompt renal biopsy to guide early initiation of life-saving therapies. To our knowledge, this is the first reported case of ANCA-negative pauci-immune necrotizing GN likely secondary to midostaurin.

Rheumatoid arthritis [RA] is a multisystem disorder in which prevalence of renal abnormalities ranges from 8 to 90%. ANCA associated pauci immune glomerulonephritis occurs as a rare late manifestation and results in poor prognosis. Most of these cases are associated with Myeloperoxidase[MPO] ANCA or previously called as p-ANCA positivity. It may occur as a part of RA associated with systemic vasculitis or an isolated disorder. We present a case of 45 year old male patient who is a known case of rheumatoid arthritis presented with renal failure and was diagnosed with Anti Neutrophill Cytoplasmic Antibody[ANCA] associated pauci immune glomerulonephritis.

Background Pauci-immune crescentic glomerulonephritis (CrGN) is one of the most common etiologies of rapidly progressive glomerulonephritis. This condition presents with crescentic glomerulonephritis with little or no immunoglobulin staining and negative serological workup aside from a positive antineutrophil cytoplasmic autoantibody (ANCA). Typically, patients with pauci-immune CrGN have an underlying systemic small vessel vasculitis, but in rare cases, it presents without any known vasculitis or ANCA. Pauci-immune ANCA negative CrGN is often strictly isolated to the kidneys. In this case, we present a patient with ANCA negative, pauci-immune CrGN with severe diffuse alveolar hemorrhage. Case presentation A 66-year-old Hispanic woman with a past medical history of controlled hypertension presented with fatigue and dysphagia. On admission, her vital signs were significant for hypoxia on room air, and her physical exam was remarkable for crackles bilaterally. The initial laboratory results revealed anemia (hemoglobin 5.2 g/dL), hyperkalemia (6.3 mmol/L), elevated creatinine (4.50 mg/dL, with a baseline of 0.9mg/dL). Urinalysis showed moderate blood and urine protein (200 mg/dL). Urine microscopic examination showed 25-50 RBCs seen/high power field. The patient was admitted to ICU due to hypoxia, a computed tomography scan of the chest/abdomen/pelvis was obtained and revealed multifocal pulmonary consolidations. A blood transfusion was ordered. The patient began to have hemoptysis and subsequent bronchoscopy showed diffuse alveolar hemorrhage. ICU team proceeded to intubate her as the hemorrhage continued to worsen. Further workup revealed a positive anti-nuclear antibodies (ANA) of 1:40, but otherwise negative serologies including myeloperoxidase (MPO)-ANCA, glomerular basement membrane antibody, and anti-double stranded DNA. Kidney biopsy showed necrotizing glomerulonephritis with crescents and negative immunofluorescence. She was diagnosed with pauci-immune ANCA-negative vasculitis with associated diffuse alveolar hemorrhage and nephritis based on these results and was started on pulse-dose steroids. The patient was started on intravenous (IV) high-dose cyclophosphamide, which helped improved the overall clinical condition significantly. After creatinine began trending down and urine output improved, the patient was discharged on a regimen of daily oral cyclophosphamide and steroid taper. Patient oxygen requirements decreased and she was sent home with supplemental oxygen while requiring 3L/min of oxygen. Conclusion Pauci-immune and ANCA-negative glomerulonephritis with concurrent diffuse alveolar hemorrhage is exceptionally rare. In this situation, medical management relied on clinical evidence from similar populations in the use of steroids and cyclophosphamide. This case report aims to shed more light on the clinical progression and management of this condition. Here we present a case of pulmonary-renal syndrome with biopsy-proven glomerulonephritis but without ANCA positive serologies.

Immune checkpoint inhibitors are increasingly used to treat a variety of solid-organ and hematologic cancers. However, overactivation of the immune system can lead to immune-related adverse events, which are increasingly recognized in the kidney. There have been only rare reported cases of checkpoint inhibitor-associated glomerulonephritis and renal vasculitis, although vasculitis in other organs has been well described. We report 4 cases of renal vasculitis or pauci-immune glomerulonephritis after checkpoint inhibitor therapy. Three patients had renal small- to medium-vessel vasculitis and 1 had focally crescentic pauci-immune glomerulonephritis. Three patients presented with acute kidney injury, and 1 presented with nephrotic syndrome and hematuria. Three patients were tested for antineutrophil cytoplasmic antibodies, which were negative. The time from checkpoint inhibitor initiation to immune-related adverse event presentation ranged from 2 weeks to 24 months. Three patients were treated with glucocorticoids, resulting in clinical resolution. Our series demonstrates that renal vasculitis and pauci-immune glomerulonephritis are important considerations in the differential diagnosis of checkpoint inhibitor-related reductions in kidney function.

There are several known mechanisms by which monoclonal Igs (MIg) or their subunits can cause kidney disease: (i) deposition in 1 or more kidney compartments, resulting in distinct clinicopathologic lesions, such as Ig-related amyloidosis, monoclonal Ig deposition disease, and a variety of glomerulonephritides, including cryoglobulinemic glomerulonephritis type I and II, immunotactoid glomerulonephritis, and proliferative glomerulonephritis with monoclonal immunoglobulin deposits; (ii) precipitation in tubular lumina (e.g., myeloma cast nephropathy); (iii) activation of the alternative pathway of complement (e.g., C3 glomerulopathy associated with monoclonal gammopathy, thrombotic microangiopathy associated with monoclonal gammopathy); (iv) cytokine activation (e.g., POEMS syndrome); and (v) crystallization in the renal vasculature (e.g., crystalglobulin-induced nephropathy).1, 2 Here, we describe an unusual case of monoclonal gammopathy of renal significance (MGRS)–associated crystalline nephropathy that does not conform to any of the previously described patterns of kidney involvement by monoclonal gammopathy.

Background: The characteristic lesion of pauci-immune glomerulonephritis is focal necrotizing and crescentic glomerulonephritis. The underlying mechanisms in the formation or progression of crescent formation need further investigations. Therefore, we aimed to evaluate the role of mammalian target of rapamycin (mTOR), which might be a potential therapeutic target, in kidney biopsies of patients with pauci-immune glomerulonephritis. Methods: The patients diagnosed as pauci-immune glomerulonephritis at an outpatient nephrology clinic were retrospectively reviewed and those patients who had a kidney biopsy before receiving an immunosuppressive treatment were included in the study. Kidney biopsy specimens were immunohistochemically stained with mTOR, antibodies of phosphatase and tensin homolog (PTEN) and transforming growth factor-β (TGF-β) and scored by an experienced renal pathologist. Results: In total, 54 patients with pauci-immune glomerulonephritis (28 [52%] female) were included. According to the histopathologic examination, 22% of our cases were classified as focal, 33% crescentic, 22% mixed, and 22% as sclerotic. The mTOR was expressed in substantial percentages of glomeruli of patients with pauci-immune glomerulonephritis. However, we observed PTEN expression in all samples and mTOR in all tubulointerstitial areas. mTOR expression was found to be related with the presence of crescentic and sclerotic changes observed in glomeruli and the degree of fibrosis in interstitial areas. Serum creatinine level or response to treatment was not found to be associated with mTOR pathway expression. Conclusion: Our results suggest that mTOR pathway may play role in the pathogenesis of pauci-immune glomerulonephritis, besides targeting this signaling may be an alternative option for those patients.

When renal biopsy reveals crescentic glomerulonephritis, differential diagnosis is wide and includes 3 immunopathologic categories of disease: immune-complex–mediated glomerulonephritis (such as IgA nephropathy, lupus nephritis, and bacterial infection–associated glomerulonephritis, particularly infectious endocarditis-associated glomerulonephritis), anti–glomerular basement membrane nephritis, and pauci-immune crescentic glomerulonephritis (associated with antineutrophil cytoplasmic antibody seropositivity in most patients). Careful integration of immunofluorescence and ultrastructural findings with the serologic tests and medical history is essential to determine the underlying cause. Rarely, crescentic glomerulonephritis occurs concomitantly with granulomatous interstitial nephritis, and the differential diagnosis in this scenario includes granulomatosis with polyangiitis and sarcoidosis. Here we report an unusual case of pauci-immune crescentic and necrotizing glomerulonephritis concurrent with granulomatous interstitial nephritis due to disseminated histoplasmosis.

Introduction: Rapidly progressive glomerulonephritis( RPGN) in children is an uncommon entity. There is paucity of studies on this. It is diagnosed with clinical features of oliguria, hematuria and renal failure in weeks. It is confirmed by finding crescents in renal biopsy. Causes of RPGN in children are different from adults. Objective of study was to identify etiology and outcome of RPGN in children. Material and Methods: It is a retrospective study conducted on 24 pediatric patients, diagnosed with RPGN at the Department of nephrology between January 2009 and December 2018 at our institute. Renal biopsy showed crescentic formations in ≥50%. Based on staining of immune deposits, biopsy was classified as immune-complex GN , pauciimmune GN and anti-glomerular basement membrane GN. Data of patients, clinical features and laboratory parameters was recorded. Factors affecting loss of renal function were identified. Results: There were 24 patients and gender ratio was 7:5 (male: female).Twenty patients had immune complex mediated GN, 3 patients had pauciimmune GN and one patient had anti GBM disease. SLE was the commonest cause of RPGN in this study. At last follow up 11 patients had advance CKD, 20 patients had hypertension and 16 patients had persistent proteinuria.Majority of the patients had fibrous or fibrocellular crescents. Need of dialysis at presentation, oliguria and percentage of fibrous or fibrocellular crescents were predictor of renal function loss. Conclusion: Immune complex GN was the commonest cause of RPGN. Majority of patients had fibrocellular or fibrous crescents. It was due to late referral. Timely intervention could improve outcome of these patients.

Background and Aims Renal involvement is a severe manifestation of ANCA-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after a first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in eGFR between diagnosis and follow-up at 3 months (ΔeGFRM0–M3) in a cohort of patients with a first flare of pauci-immune glomerulonephritis. Methods This was a retrospective study over the period 2003–2018 of incident patients in the Nord-Pas-de-Calais (France). Patients were recruited if they had a first histologically-proven flare of pauci immune glomerulonephritis with at least 1 year of follow up. Kidney function was estimated with MDRD-equation and analysed at diagnosis, 3rd, 6th and 12th months. The primary outcome was ΔeGFRM0–M3. Factors evaluated were histological (Berden classification, interstitial fibrosis, percentage of crescents), clinical (extra-renal manifestations, sex, age) or biological (severity of acute kidney injury, dialysis, ANCA subtype). Results One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs 28 ± 26 ml/min/1.73 m2, p < 0.001), with a ΔeGFRM0–M3 of 12 ± 19 ml/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs 40 ± 24 ml/min/1.73m2, p = 0.003). The factors significantly associated with ΔeGFRM0–M3 in univariate analysis were: sclerotic class according to Berden classification, percentage of interstitial fibrosis, percentage of cellular crescents, acute tubular necrosis, neurological involvement. The factors associated with ΔeGFRM0–M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in eGFR was 2.90 ± 0.06 ml/min/1.73m2 for every 10-point gain in the percentage of cellular crescents. ΔeGFRM0–M3 was not associated with the risks of end-stage renal disease or death in long-term follow-up. Conclusions Early renal recovery after a first flare of pauci-immune glomerulonephritis occurred mainly in the first three months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.

Background and Aims Macrophages and monocytes are main players in innate immunity. In renal diseases, their role is poorly understood. Our multicentric cross-sectional study aimed to study the prevalence of macrophages and monocytes in various human native kidney diseases. For this, we used precise pixel-based digital quantification of their densities in renal biopsies and correlated our findings with clinical data. Method We included 324 patients, who underwent a diagnostic renal biopsy. Additional normal kidney samples from 16 tumour nephrectomies were used as controls. According to the diagnosed diseases, we established 17 patient groups. Biopsies were stained for CD68+-macrophages using automated immunohistochemistry (Ventana Ultra) and selected groups were further subtyped for CD14+-monocytes and CD163+-M2-macrophages (67 cases, pauci-immune glomerulonephritis (PIGN), IgA-nephropathy (IgAN) and control samples). Digitized sections (Leica) were analysed using the open-source software QuPath to quantify cell densities (positively stained areas displayed as percentages of ROI) in renal cortex, medulla and extrarenal tissue, respectively. Detailed clinical and laboratory data at timepoint of biopsy were available for all patients. Additional data for follow-up were achievable in 158 cases. Results Renal disease samples presented higher mean macrophage densities compared to control cases (CD68: cortex 1.2 vs. 0.2%, p64 years) showed a higher medullary M2-infiltration (1.81% vs. 4.34%, p Conclusion Macrophages may promote progression of human renal diseases, whereas monocytes do not correlate with eGFR-decline. Especially, in cANCA- vasculitis CD163+- infiltration is associated with renal outcome. Additional studies are needed to investigate, whether macrophages can serve as predictive markers or therapeutical targets in native renal diseases.

Introduction: Coronavirus disease is a multi-organ disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2). Although acute kidney injury, collapsing glomerulopathy and thrombotic micro-angiopathy have been frequently attributed to COVID-19, pauci-immune glomerulonephritis (GN) has rarely been described [1]. Here we report a case of pauci-immune GN associated with SARS-CoV-2. Case Presentation: A 53 years old female with hypertension, diabetes mellitus, hepatitis C (treated 6 years ago), and recent covid-19 pneumonia (3 months ago), presented with dysuria, nausea, and vomiting. She denied fever, flank pain, and hematuria. The laboratory workup showed elevated blood urea nitrogen BUN 82 mg/dl and creatinine Cr 9.8 mg/dl (baseline creatinine was 0.9 mg/dl three months ago). Urinalysis showed proteinuria >1000 mg/dl and urine protein creatinine ratio of 5.3 (normal < 0.1), concerning for glomerulonephritis. Serological evaluation for glomerular disease showed normal complements C3 and C4, normal titers of anti-neutrophil cytoplasmic antibodies including p-ANCA, c-ANCA, atypical ANCA, and cryoglobulins. Screening for Hepatitis B and Hepatitis C was negative. The remainder of the autoimmune workup was unremarkable including Rheumatoid factor, Anti CCP antibodies (Ab), Anti Ribo-nucleoprotein Ab, and Anti Glomerular basement membrane antibodies. Coronavirus PCR was negative and qualitative IgG was reactive. CT chest showed idiopathic pulmonary fibrosis (IPF) and resolving ground glass opacities from prior coronavirus infection. CT abdomen and pelvis was unremarkable for obstructive uropathy. The renal biopsy showed pauci-immune focal sclerosis with 20% fibro-cellular crescents diagnostic for pauci-immune glomerulonephritis. The patient was treated for pauci-immune glomerulonephritis with pulse-dose intravenous steroids (methylprednisolone) followed by oral prednisone and rituximab. The renal functions improved dramatically (on day 15, her creatinine down-trended to 4 mg/dl from 9mg/dl on admission). She did not require intermittent hemodialysis and was discharged on day 15 with outpatient follow up. Discussion: The mechanisms of acute kidney injury in COVID-19 include renal hypoperfusion, endothelial dysfunction, micro-thrombi, and cytopathic effects of SARS-CoV-2 towards renal tubules and glomeruli. Due to a lack of scientific evidence related to coronavirus disease, the management of glomerulopathy is challenging. The existing literature favors the use of anti-viral therapy with immunosuppressive agents without the concern of worsening infection [2].

Background Crescentic glomerulonephritis is a disease characterized by severe glomerular injuries that is classified into five different pathological types. Patients with type V disease have pauci-immune crescentic glomerulonephritis (PICGN) that is negative for anti-neutrophil cytoplasmic autoantibodies (ANCAs). There are limited clinical data on the manifestations, treatment, and prognosis of type V crescentic glomerulonephritis, especially in children. Case presentation A 13-year-old girl who had an intermittent fever for more than 10 months was admitted to our hospital. She had no gross hematuria, oliguria, edema, or hypertension, but further tests indicated a decreased glomerular filtration rate, hematuria, proteinuria, and an elevated level of IL-6. The antinuclear antibody spectrum test was positive at 1:1000, and the ANCA and anti-glomerular basement membrane antibody tests were negative. A renal biopsy confirmed the diagnosis of ANCA-negative PICGN. We administered methylprednisolone pulse therapy with intravenous cyclophosphamide and oral mycophenolate mofetil. At the 3-month follow-up, her urine protein level was significantly lower, and her serum creatinine level was in the normal range. Conclusions Fever may be an extrarenal manifestation of ANCA-negative PICGN, and IL-6 may play a role in the pathogenesis of this disease. Early methylprednisolone pulse therapy with an immunosuppressant may reduce symptoms and improve prognosis.

Renal-limited pauci-immune necrotizing glomerulonephritis presenting as acute encephalopathy is a rare occurrence. A 67-year-old Hispanic male presented to the hospital after being found down. He was found to have acute renal failure and high anion gap metabolic acidosis. Hemodialysis did not improve his encephalopathy. A vasculitis workup resulted in a high antimyeloperoxidase (MPO) antibody level. Renal biopsy revealed globally sclerotic glomeruli with focal thickened capillary loops, suggestive of pauci-immune necrotizing and crescentic glomerulonephritis (GN). Treatment consisted of high dose methylprednisolone and rituximab for induction, and three cycles of plasmapheresis, in addition to hemodialysis for uremia. Upon discharge, he was continued on hemodialysis and continued treatment with prednisone. Patients who present acutely with persistent uremic encephalopathy despite hemodialysis may warrant pursuing an alternative diagnosis, such as glomerulonephritis. Prompt diagnosis and treatment are necessary to improve the prognosis since untreated pauci-immune glomerulonephritis carries a high mortality rate.

BackgroundRapidly 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).MethodsClinical 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.ResultsIn 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, pConclusionIn 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.

Pauci-immune crescentic glomerulonephritis is the most common variant of rapidly progressive glomerulonephritis, accounting for approximately 80% of total cases. Most of the cases are associated with the presence of anti-neutrophil cytoplasmic antibody (ANCA) and are usually referred to as ANCA-associated vasculitis. A 68-year-old male with no previous renal history presented with complaints of shortness of breath, cough, and bilateral leg swelling for 2 weeks. Initial workup was significant for creatinine elevated at 2.9 mg/dL, blood urea nitrogen at 65 mg/dL, and glomerular filtration rate of 27 mL/min. Further workup was unremarkable for any significant abnormality. Subsequently patient’s kidney function worsened, and temporary hemodialysis was started. Kidney biopsy was performed, which later came back significant for necrotizing arteritis, multifocal, with focal necrotizing and crescentic glomerulonephritis, pauci-immune type. High-dose corticosteroids were administered, and good clinical response was noticed. This is a very rare case of renal limited pauci-immune crescentic glomerulonephritis with annual incidence of 7 to 10 cases per million every year in the United States. The absence of involvement of other organs makes our case even rarer. Mortality is as high as 90% in untreated patients and aggressive therapy with glucocorticoids and cyclophosphamide or rituximab are the mainstay of treatment. The presence of significant renal impairment in the absence of other organs involvement in our patient makes it a very unique presentation of ANCA-positive vasculitis.

Coronavirus disease 2019 (COVID-19) is a pandemic caused by a novel coronavirus that has been identified to belong to the β-coronavirus family.1 As the COVID-19 pandemic continues to evolve, more aspects of this illness are being defined and described. In the United States, the incidence of acute kidney injury (AKI) in patients hospitalized with COVID-19 has been reported to be around 37%.2 Different autopsy and kidney biopsy series have revealed acute tubular injury (ATI) to be the most common renal pathology lesion in these patients.3,S1 Although cases of collapsing glomerulopathy and thrombotic microangiopathy (TMA) with COVID-19 have been reported,4,5 an association between COVID-19 and crescentic glomerulonephritis (GN) has rarely been described.6 Herein, we report 2 cases of pauci immune GN with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, who clinically improved with treatment of COVID-19 and cautious use of immunosuppressants.

The glomerulonephritis (GN) of granulomatosis polyangiitis is described as "pauci immune" because the glomeruli show little or no evidence of immune complex deposition by immunofluorescence or electron microscopy. Here we describe a severe crescentic GN in which the patient was myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA) positive, and on renal biopsy the glomeruli were pauci immune (there were only a few electron-dense deposits). However, by immunofluorescence the glomeruli showed "full-house" staining (the glomeruli stained positive for C1q, C3, IgG, IgA, and IgM). The latter staining pattern would be consistent with that seen in patients with lupus-like GN or with severe crescentic GN as a result of bacterial infection. So, should this patient receive high-dose immunosuppressive therapy and steroid therapy to treat presumed autoimmune GN, or should the patient receive intensive antibiotic therapy to treat a presumed underlying severe infection? This dilemma was soon resolved because the patient's blood culture returned positive for Streptococcus mutans and cardiac echo showed evidence of bacterial endocarditis. This report provides further detail regarding the patient's clinical issues.

Infective endocarditis (IE) is more common in patients with predisposing cardiac lesions and has many potential complications, including stroke and arterial thromboembolisms. Renal manifestations have an estimated prevalence of ∼20%. Rapidly progressive glomerulonephritis (RPGN) is a nephrological emergency manifested by autoimmune-mediated progressive loss of renal function over a relatively short period of time. Here, we report the case of a 60-year-old Caucasian male, who presented with speech impairment and was found to have multiple embolic strokes caused by aortic valve IE. His renal function declined rapidly, and his urine sediment featured hematuria and proteinuria. ANCA titer was negative by immunofluorescence (IF); however, the PR3 antibody was elevated. The renal biopsy revealed pauci-immune focally necrotizing glomerulonephritis with the presence of ∼25% cellular crescents. He was initially treated with plasmapheresis and pulse dose steroids. Hemodialysis was initiated for uremic symptoms. After four weeks of antibiotic therapy and with blood cultures remaining negative, he was treated with rituximab. Two months after discharge, his renal function showed improvement, and hemodialysis was discontinued. This case highlights several complications associated with lactobacillus endocarditis including RPGN.

Background and Aims Pauci-immune glomerulonephritis (GN), usually associated with circulating antineutrophil cytoplasm antibodies (ANCA), is one of the most common causes of rapidly progressive glomerulonephritis that results in high incidence of end-stage kidney disease (ESKD). Most of the existing large trials looking at treatment efficacies exclude ANCA-negative patients, and relatively few studies have reported their long-term outcomes. Therefore, we conducted a single-centre retrospective study to examine the long-term overall survival and renal outcome in this cohort of patients. Method All cases of newly diagnosed biopsy-proven pauci-immune GN from 2006 - 2019 were identified through a local histopathology database. Patients with negative anti-myeloperoxidase (MPO) and anti-proteinase-3 (PR3) serology were identified (ANCA-negative group) and comparisons made with the cohort of patients with positive serology (MPO/PR3 positive group). Patients with relapsing ANCA-GN, eosinophilic granulomatosis with polyangitis, other co-existing glomerulonephritis or missing data on induction therapy or outcome were excluded. Baseline demographics, initial serum creatinine (sCr), estimated glomerular filtration rate (eGFR), systemic involvement and histopathology features including percentage normal glomeruli, and interstitial fibrosis/tubular atrophy score of >25% were collected and compared. Kaplan Meier survival analysis was used to compare overall survival and end-stage kidney disease (ESKD) progression rate between the two groups. Results 178 patients were identified with a median follow-up of 44 months. 83 were female (47%) and median age was 62 years. 15 (8%) were ANCA-negative. 163 (92%) were MPO- and/or PR3-ANCA positive. There were no differences in baseline characteristics such as age, gender and proportion of patients with normal glomeruli 25% on renal biopsy (53% with >25% IFTA in ANCA-negative cohort vs 27%, p =0.03). The ANCA-negative group were more likely to receive combination immunosuppressive therapy that included plasma exchange (47% vs 23%, p value 0.04). When considering overall survival there was significantly higher mortality (40% vs 16%, p value 0.009) and rate of progression to ESKD (53% vs 18%, p value 0.001) in the ANCA-negative group as a whole. When we compared patients with renal-limited vasculitis only however, there was no significant difference in either overall survival or rate of progression to ESKD (p=0.85 and 0.84 respectively). We found that ANCA-negative patients with systemic disease did still have significantly higher rates of both progression to ESKD and overall mortality (p=0.002 and p=0.02 respectively). Conclusion In our cohort, patients with ANCA-negative pauci-immune GN have poorer renal function and higher IFTA scores on biopsy at presentation perhaps reflecting delayed diagnosis due to a lack of diagnostic serology and the higher proportion of renal-limited disease in this subgroup. Despite intensive immunosuppressive therapy, this study observed overall higher treatment failure rates in ANCA-negative patients, largely in those with systemic disease. This possibly relates to a different underlying disease process. Larger, prospective studies are required to enhance understanding of the disease pathogenesis to allow optimal tailored treatment for these patients.

Background and Aims Severe kidney involvement represents a frequent clinical scenario for patients with pauci-immune (PI) vasculitis. We aimed to explore the factors, which are associated with prognosis, in short and long term, following administration of appropriate immunosuppressive therapy. Method Patients were included if they had biopsy proven PI glomerulonephritis (GN) with estimated GFR20 ml/min/1.73 m2 with no signs of vasculitis. Histopathological evaluation included arteriosclerosis, % of normal glomeruli, activity index, chronicity index. Results A total of 83 patients, with a mean age of 59.6 (15.05) years were included. There were, 45 males (54.2%). After 3 months, 59 patients (71.1%) had responded to immunosuppressive therapy, 16 (19.3%) were dialysis depended, 5(6.02%) died and 2 were lost in follow up. By the end of the 1st year, 59 patients (71.1%) achieved remission, 16(19.3%) ended up in ESKD and 6(7.4%) died. Factors which were associated with treatment response included MPO-ANCA positivity [odds ratio OR:3.9, 95%CI (1.13-13.37) p=0.03], eGFR>10ml/min/1.73m2 at presentation [OR:2.5, 95% CI(0.86-7.30), p=0.009], normal glomeruli >10% [OR:3.8, 95%CI (1.24-12.1), p=0.02], and chronicity index more than 6 [OR:6.2, 95% CI(1.77-22.4), p=0.004]. Risk factors associated with ESKD included non-response to immunosuppressive therapy [Relative Risk RR:0.05, 95%CI (0.01-0.2) p75 years [RR:3.2, 95% CI (0.9-10.6) p=0.055]. Two of the 6 deaths were disease related. Conclusion A significant proportion of patients with PI-GN, who presented with severe renal dysfunction, responded to immunosuppressive therapy and recovered renal function approximately 3 months after initiation of therapy. The most important risk factors for ESKD were age>75 years

Background and Aims Pauci-immune crescentic glomerulonephritis is rare form of glomerulonephritis that frequently presents as rapidly progressive renal failure. The histopathological classification proposed by Berden a decade earlier described difference in the outcomes of patients in the focal, crescentic, mixed and sclerotic category with best prognosis for focal and worst for sclerotic group. The newly proposed renal risk score (Brix SR at al.) takes into account both the histopathological parameters (% of normal glomeruli, tubular atrophy and interstitial fibrosis) and clinical parameter (eGFR) which influence outcome in these patients. Present study was undertaken to determine outcomes of pauci-immune crescentic glomerulonephritis based on both of these prognostic systems and also to determine effect of individual risk factors on renal outcome. Method 64 patients diagnosed as pauci-immune crescentic glomerulonephritis from January 2013 to December 2018 were retrospectively analyzed. There histopathological slides were reviewed for percentage normal glomeruli, extent of interstitial fibrosis and tubular atrophy and biopsies were also grouped according to histopathological classification into focal, crescentic, mixed and sclerotic categories. The clinical parameters including serum creatinine, eGFR at time of biopsy and follow-up, and status of ANCA positivity were obtained from electronic records. Renal biopsies were scored based on renal risk score depending on the % of normal glomeruli (>25%,10-25% and 25%) and eGFR(>15ml/min,≤15ml/min) into 3 risk categories. Results There were 61 adult patients and 3 pediatric patients. Two patient with insufficient glomeruli ( Conclusion In our study of Pauci-immune crescentic glomerulonpehritis ANCA was negative in 35% cases. Percentage of normal glomeruli, IFTA and eGFR at time of biopsy were important histopathological and clinical risk factors influencing renal survival in these patients. Results of our study validate that recently proposed renal risk score is a better predictor of survival (p=0.002) as compared to histological classification proposed by Berden (p=0.046).

Background and Aims Crohns disease is a chronic transmural inflammation which can affect any segment of the gastrointestinal tract in a discontinuous fashion. Treatment for crohns include steroids, Immunosuppresants (thiopurines and methotrexate) and biological agents such as TNF antagonist (adalimumab, infliximab and certrolizumab pegol) and anti-integrin antibodies (natalizumab and vedolizumab). However in cases of refractory disease the management can become difficult. In such case, use of Ustekinumab is indicated. Tumour necrosis factor-alpha are first line biological agents for managing adult patients with moderate to severe disease . We present a rare case of Ustekinumab treatment and onset of renal disease secondary to crescentic glomerulonephritis in a 37-year-old female. We aim to discuss the presentation, diagnosis and management of the above condition. To the best of our knowledge, this type of presentation has not been described in existing literature. Method Patient’s hospital case records and GP correspondence were used to analyze this case. Results This is a case of a 37-year-old female with a four year history of refractory crohns disease affecting colon and terminal ileum. She was treated with numerous treatment modalities such as budesonide, mesalazine, azathioprine, mercaptopurine, adalimumab and vedolizumab over the years. However, these treatments were not successful as she had multiple hospital admissions every year with flare up of crohns requiring intravenous steroids. In January 2018, she was again admitted to hospital with a flare up of Crohns disease. Colonoscopy and imaging confirmed active disease with moderate severity. Further treatment strategies were discussed and Ustekinumab was decided as the best next treatment option. She had her first intravenous infusion in February 2018 and was planned for injections every 3 months. Her symptoms of Crohns disease improved with the Ustekinumab injections. After her second injection of Ustekinumab in May 2018, repeat blood tests showed acute kidney injury with creatinine of 127 umol/l from a baseline of 75 umol/l and a urea of 8.3 mmol/l from a baseline of 3 mmol/l. Urine dip in May was positive for protein and blood. She was referred to the renal team as an outpatient on the basis of these results for further management. Urea and creatinine had worsened to 10.4 mmol/l and 168 umol/l respectively. Urine protein creatinine ratio was 200. The initial impression was drug induced vasculitis versus Acute kidney injury (AKI) secondary to diarrhoea and poor intake. Considering the possibility of glomerulonephritis, serology testing for immunoglobulins, complements, blood and urine electrophoresis, ANA, ANCA, anti-GBM and viral serology tests were arranged, which all came back negative. ultrasound-guided percutaneous kidney biopsy was performed. Renal biopsy confirmed the diagnosis of pauci-immune glomerulonephritis with crescents (vasculitis). A diagnosis of Ustekinumab induced ANCA negative crescentic glomerulonephritis was established. Ustekinumab was discontinued and she was treated with prednisolone 60mg for four weeks, followed by tapering regime for 6-12 weeks in the community. Renal function improved with a creatinine of 120 umol/l, two months after stopping Ustekinumab. Repeated blood tests during these two months showed a steady and gradual decline in creatinine and eventually return back to normal level of 80 umol/l. Urinalysis showed proteinuria settling with no evidence of haematuria. Conclusion/learning points

Cancer immunotherapy is rapidly changing the treatment paradigm in oncology, and immune checkpoint inhibitors (ICPIs) have been used successfully in a variety of cancer types. Specific side effects termed immune-related adverse events (irAEs) have now been described in various organ systems, including the kidney. Renal complications have rarely been reported compared with other irAEs and mostly consist of acute interstitial nephritis. Only rare cases of ICPI-related glomerulonephritis have been described. Herein, we report the case of an adult patient treated with pembrolizumab (anti-PD-1) for squamous cell carcinoma (SCC), who developed infectious enterocolitis, and ANCA-related with diffuse necrotizing crescentic glomerulonephritis, both conditions potentially linked to treatment with pembrolizumab.

Objectives: To assess whether the histopathological features of the synovium before starting treatment with the TNFi certolizumab-pegol could predict clinical outcome and examine the modulation of histopathology by treatment. Methods: Thirty-seven RA patients fulfilling UK NICE guidelines for biologic therapy were enrolled at Barts Health NHS trust and underwent synovial sampling of an actively inflamed joint using ultrasound-guided needle biopsy before commencing certolizumab-pegol and after 12-weeks. At 12-weeks, patients were categorized as responders if they had a DAS28 fall >1.2. A minimum of 6 samples was collected for histological analysis. Based on H&E and immunohistochemistry (IHC) staining for CD3 (T cells), CD20 (B cells), CD138 (plasma cells), and CD68 (macrophages) patients were categorized into three distinct synovial pathotypes (lympho-myeloid, diffuse-myeloid, and pauci-immune). Results: At baseline, as per inclusion criteria, DAS28 mean was 6.4 ± 0.9. 94.6% of the synovial tissue was retrieved from the wrist or a metacarpophalangeal joint. Histological pathotypes were distributed as follows: 58% lympho-myeloid, 19.4% diffuse-myeloid, and 22.6% pauci-immune. Patients with a pauci-immune pathotype had lower levels of CRP but higher VAS fatigue compared to lympho- and diffuse-myeloid. Based on DAS28 fall >1.2, 67.6% of patients were deemed as responders and 32.4% as non-responders. However, by categorizing patients according to the baseline synovial pathotype, we demonstrated that a significantly higher number of patients with a lympho-myeloid and diffuse-myeloid pathotype in comparison with pauci-immune pathotype [83.3% (15/18), 83.3 % (5/6) vs. 28.6% (2/7), p = 0.022) achieved clinical response to certolizumab-pegol. Furthermore, we observed a significantly higher level of post-treatment tender joint count and VAS scores for pain, fatigue and global health in pauci-immune in comparison with lympho- and diffuse-myeloid patients but no differences in the number of swollen joints, ESR and CRP. Finally, we confirmed a significant fall in the number of CD68+ sublining macrophages post-treatment in responders and a correlation between the reduction in the CD20+ B-cells score and the improvement in the DAS28 at 12-weeks. Conclusions: The analysis of the synovial histopathology may be a helpful tool to identify among clinically indistinguishable patients those with lower probability of response to TNFα-blockade.

We present a case report of a patient with Isolated pauci-immune pulmonary capillaritis (IPIPC). A 40-year-old male presented with acute onset severe hypoxemic respiratory failure. He had just returned home from work as a cabinetmaker, where he experienced inhalational exposure to hydrocarbons and solvents, and had smoked a marijuana cigarette. He was hypotensive, and his chest imaging showed bilateral dependent infiltrates. His hypoxemia made little improvement after conventional ventilator support and broad-spectrum antibacterial therapy and he was considered too unstable to tolerate diagnostic bronchoscopy with bronchoalveolar lavage. His laboratory evaluation initially showed microscopic hematuria which later cleared, but other tests including serologic autoimmune assessment were negative, and he did not have any traditional risk factors for vasculitis. A video-assisted thoracoscopic lung biopsy revealed diffuse alveolar hemorrhage with pulmonary capillaritis on histopathology. He was diagnosed with IPIPC and initiated on immunosuppressive therapy. He was soon liberated from mechanical ventilation and improved to hospital discharge. Diffuse alveolar hemorrhage from Goodpasture’s Syndrome has manifested following inhalation of hydrocarbons and following smoking. This has not previously been reported with IPIPC. Given the lack of other findings and risk factors, his IPIPC was likely associated with occupational exposures to hydrocarbons as a cabinetmaker compounded by marijuana smoking.

Background: Heavy proteinuria in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is usually considered to be associated with immune deposits in renal biopsy. Nephrotic ANCA GN without immune deposits (pauci-immune) is rare and has not been studied specially. In this study characteristics of these patients are to be investigated. Methods: Clinical and pathological characteristics from 20 kidney biopsy-proven pauci-immune anti-myeloperoxidase antibody-associated GN patients with nephrotic proteinuria were analyzed and were compared with ANCA GN patients without nephrotic proteinuria. Results: Acute kidney injury (AKI) and gross hematuria were much prevalent but extra-renal involvement was less prevalent in pauci-immune ANCA GN with nephrotic proteinuria than in pauci-immune ANCA GN without nephrotic proteinuria. No more severe hypoalbuminemia, hypercoagulability, hyperlipidemia or higher thrombosis incidence were found between two groups. Compared with patients without nephrotic proteinuria, patients with nephrotic proteinuria had more prevalent crescentic category in histopathology. Proteinuria decreased quickly after treatment but much poorer renal prognosis was found in pauci-immune ANCA GN with nephrotic proteinuria. The results of urinary albumin to total protein ratio and urinary protein electrophoresis showed pauci-immune ANCA GN with nephrotic proteinuria had obvious non-selective proteinuria. Conclusions: Pauci-immune ANCA GN with nephrotic proteinuria do not have more severe hypoalbuminemia, hypercoagulability or hyperlipidemia than patients without nephrotic proteinuria. Non-selective proteinuria might be the reason. However, pauci-immune ANCA GN with nephrotic proteinuria have more prevalent crescentic category in histopathology, higher incidence of AKI, gross hematuria and poorer renal prognosis despite of good sensitivity to therapy of proteinuria.

Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of pauci-immune renal vasculitis. However, in 10% of the cases, ANCA are absent. We present a case of a 64-year-old man with a chronic untreated hepatitis C virus infection and Middle Eastern thalassemia who was ANCA-negative when he was hospitalized due to acute kidney injury and accounts for an uncommon presentation of renal vasculitis. The patient had earlier reported to have undergone local lobectomy and adjuvant chemotherapy (carboplatin/pemetrexed) for lung adenocarcinoma a month prior. IL-6 has been reported to be involved in the pathophysiological cascade causing pauci-immune glomerulonephritis amongst non-small cell lung cancer patients. Previous studies with subgroup analysis have demonstrated that ANCA negativity has been associated with more chronic glomerular lesions and less crescent formation, which tends to have a critical outcome in the renal system. However, our patient underwent kidney biopsy exhibiting active crescentic glomerulonephritis, pauci-immune type with 5 cellular crescents amongst 15 glomeruli. To our knowledge, this is the third reported case of ANCA-negative vasculitis with typical presentation on biopsy in non-small cell lung cancer patients.

While methimazole (MMI) is the first line treatment for hyperthyroidism, this medication is not devoid of adverse effects. In this article, we present a 70-year-old male who admitted the hospital with right lower extremity pain and rash. The patient was recently treated with MMI for hyperthyroidism. Imaging studies revealed bilateral renal and splenic infarcts along with thrombosis of popliteal artery. Laboratory data revealed hematuria and proteinuria with positive (MPO), anti-proteinase-3 (PR3) and anti-cardiolipin IgG antibodies. Renal biopsy revealed pauci-immune glomerulonephritis and features with anti-phospholipid antibody syndrome (APS). MMI was discontinued and the patient was treated successfully with steroid therapy and anti-coagulation with resolution of proteinuria, hematuria and normalization of laboratory parameters. While MMI-induced pauci-immune glomerulonephritis has been previously reported, its association with APS has never been described before. Our case demonstrates that this rare diagnosis can be treated by early withdrawal of MMI and initiation of steroids along with anticoagulation.

We report a case of systemic lupus erythematosus (SLE) who presented with rapidly progressive renal failure (RPRF) with positive antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA) antibody and active urinary sediment in the form of microscopic hematuria and proteinuria. Provisional clinical diagnosis of lupus nephritis was made. Renal biopsy showed pauci-immune crescentic glomerulonephritis, the diagnosis of which was supported by positive serum anti-MPO antibody. Renal biopsy in SLE patients can sometimes reveal varied pathological entities such as antinuclear cytoplasmic antibodies (ANCAs) positive vasculitis, as in our case, which modified our treatment protocol. Thus, in a patient with SLE presenting with RPRF with active urinary sediments, ANCA serology, and renal biopsy with immunofluorescence examination should be performed always.

Background: Crescents indicate active disease with rapidly deteriorating renal function. Many primary renal diseases can be associated with crescents, however only a few conditions presents as crescentic glomerulonephritis (CrGN). The incidence varies in different population. Aims and objective: The aim of the study was to know the incidence of CrGN and that of crescents in various glomerulopathies along with their clinicopathological associations. Material and methods: Renal core biopsies over 5 year period were collected retrospectively from pathology archives and reviewed for crescents and CrGN. Clinical, serological, Immunoflourescence and follow up details were collected. Results: A total of 1629 renal biopsies were received. Crescents were identified in 9.69% and 2.08% were CrGN. Males and females were equally distributed. Paediatric population constituted 24%. The most common presentation was nephritic syndrome. Cellular crescents were seen in 81 cases, fibro cellular/ fibrous in 55 cases and both in 22 cases. In immune complex(IC) mediated group, lupus nephritis (LN) showed crescents in 31.7%, followed by PIGN (29.67%) and IgAN (25.2%). Vasculitis group had 79% crescents. All cases of anti GBM disease and pauci immune ANCA negative renal limited vasculitis (PI-RLV) had crescents. The most common CrGNs were anti GBM disease (100%), followed by vasculitis (37%) and PI-RLV (33%) and least in IC group (5% in PIGN and IgAN and 3.5% in LN). Complete remission was seen in 32.2%. Conclusion: Crescents in renal biopsies are not rare. Although CrGN is more common in vasculitis and anti-GBM disease, the incidence of IC-GN is more in our population and a significant number may show crescents.

Antineutrophil cytoplasmic antibody (ANCA) has been known to cause pauci-immune crescentic glomerulonephritis. In addition, several reports described membranous glomerulonephritis (MN) concurrent with ANCA-associated glomerulonephritis. Because the two glomerular diseases simultaneously appear in an ANCA-positive patient, the mechanisms whereby ANCA causes the two different glomerular diseases remain ambiguous. Herein, we report a case of 19-year-old man who presented with hematuria, pre-nephrotic proteinuria, and high titer of myeloperoxidase (MPO)-ANCA. The first renal biopsy revealed MN with chronic glomerular scar lesions of unknown etiology. Predominant immunoglobulin (Ig) G1 subclass and negative phospholipase-A2 receptor staining, together with granular-positive glomerular capillary co-localization of MPO and IgG staining, suggested secondary MN due to MPO-MPO-ANCA immune-complex. Five years later, the patient presented with fever, severe renal dysfunction, and alveolar hemorrhage with high titer of MPO-ANCA that indicated pulmonary renal syndrome due to ANCA-associated vasculitis. The second renal biopsy revealed pauci-immune crescentic glomerulonephritis without either apparent MN-lesion or glomerular IgG staining. This is the first reported case showing that MPO-ANCA caused two different glomerular diseases, MN and pauci-immune crescentic glomerulonephritis, in the same patient at the different time points. Our case indicated that common MPO-ANCA might cause different glomerular diseases by different immune mechanisms.

Renal involvement in non-Hodgkin lymphoma, especially mantle cell lymphoma (MCL) is rare. A 77-year-old man presented with acute kidney injury (AKI), which rapidly progressed to dialysis dependence. Kidney biopsy revealed patchy B-cell lymphocytic aggregates in the interstitium, which were positive for cyclin D1, consistent with atypical CD5-negative MCL as confirmed by the detection of translocation t(11;14) by FISH. Crescents were noted in 3 of 26 glomeruli; while PR-3 antineutrophil cytoplasmic antibody (ANCA) positivity and negative immunofluorescence suggested an additional pauci-immune (rapidly progressive) glomerulonephritis pattern of injury. Patient received chemotherapy (cyclophosphamide, vincristine, and prednisone), which improved his renal function and allowed for discontinuation of hemodialysis. However, he died from pulmonary hemorrhage 8 months after initial presentation. This is the first reported case of a patient with coexistence of renal MCL infiltration and ANCA-positive pauci-immune glomerulonephritis.