scholarly journals Proteinuria Indicates Decreased Normal Glomeruli in ANCA-Associated Glomerulonephritis Independent of Systemic Disease Activity

2021 ◽  
Vol 10 (7) ◽  
pp. 1538
Author(s):  
Désirée Tampe ◽  
Peter Korsten ◽  
Philipp Ströbel ◽  
Samy Hakroush ◽  
Björn Tampe
Keyword(s):  
Disease Activity ◽  
Systemic Disease ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Clinicopathological Characteristics ◽  
Renal Outcome ◽  
Study Results ◽  
Renal Biopsies ◽  
Stage Renal Disease

Background: Renal involvement is a common and severe complication of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), potentially resulting in a pauci-immune necrotizing and crescentic ANCA glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. There is recent evidence that the degree of proteinuria at diagnosis is associated with long-term renal outcome in ANCA GN. Therefore, we here aimed to systematically describe the association between proteinuria and clinicopathological characteristics in 53 renal biopsies with ANCA GN and corresponding urinary samples at admission. Methods: A total number of 53 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included from 2015 to 2021 in a single-center study. Results: Proteinuria correlated with myeloperoxidase (MPO) subtype, diagnosis of microscopic polyangiitis (MPA) and severe deterioration of kidney function. Proteinuria was most prominent in sclerotic class ANCA GN and ANCA renal risk score (ARRS) high risk attributed to nonselective proteinuria, including both glomerular and tubular proteinuria. Finally, there was no association between proteinuria and systemic disease activity, suggesting that proteinuria reflected specific renal involvement in AAV rather that systemic disease activity. Conclusions: In conclusion, proteinuria correlated with distinct clinicopathological characteristics in ANCA GN, mostly attributed to a reduced fraction of normal glomeruli. Furthermore, proteinuria in ANCA GN reflected specific renal involvement in AAV rather than systemic disease activity. Therefore, urinary findings could further improve our understanding of mechanisms promoting kidney injury and progression of ANCA GN.

scholarly journals Neutrophils associate with Bowman’s capsule rupture specifically in PR3-ANCA glomerulonephritis

2021 ◽  
Author(s):  
Samy Hakroush ◽  
Björn Tampe
Keyword(s):  
Plasma Cells ◽  
Immune Cell ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Stage Renal Disease ◽  
End Stage ◽  
Bowman's Capsule ◽  
Tubulointerstitial Inflammation ◽  
Capsule Rupture

Abstract Background Renal involvement is a common and severe complication of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) potentially resulting in a pauci-immune necrotizing and crescentic antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We recently described that Bowman’s capsule rupture links glomerular damage to tubulointerstitial inflammation in ANCA-associated glomerulonephritis. Herein we provide a comprehensive histological subtyping of immune cell infiltrates in association with Bowman’s capsule rupture in ANCA GN. Methods A total of 44 kidney biopsies with ANCA GN were retrospectively included in a single-center observational study. Within a renal biopsy specimen, each glomerulus was scored separately for the presence of extensive and focal Bowman’s capsule rupture in injured glomeruli. Infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the area of total cortical inflammation. Results Extensive Bowman’s capsule rupture was associated with tubulointerstitial inflammation containing infiltrates of neutrophils, eosinophils and plasma cells. A similar association was observed for the presence of focal Bowman’s capsule rupture, correlating with tubulointerstitial inflammation containing neutrophils, eosinophils and plasma cells. Multiple logistic regression confirmed that extensive Bowman’s capsule rupture correlated with tubulointerstitial inflammation containing neutrophils, and focal Bowman’s capsule rupture correlated with neutrophil and plasma cell infiltration. Furthermore, this association was specifically observed in PR3-ANCA GN. Conclusion To our knowledge, this is the first report linking Bowman’s capsule rupture directly to tubulointerstitial inflammation by immune cell subtypes. This underscores a pathomechanistic link between tubulointerstitial and glomerular lesions in ANCA GN and needs further investigation. Graphical abstract

Microscopic Polyangiitis: New Insights into Pathogenesis, Clinical Features and Therapy

2018 ◽  
Vol 39 (04) ◽  
pp. 459-464 ◽  
Author(s):  
Alexandre Karras
Keyword(s):  
Microscopic Polyangiitis ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Cause Of Deaths ◽  
Optimal Maintenance ◽  
General Signs ◽  
Rapidly Progressive Renal Failure ◽  
Stage Renal Disease ◽  
End Stage

AbstractMicroscopic polyangiitis (MPA) is one of the main clinical presentations of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Although the disease is defined by clinical and pathological criteria, the anti-myeloperoxidase (MPO) specificity of ANCAs is observed in almost 80% of MPA patients. The direct pathogenic role of anti-MPO antibodies has been proven in animal models, in which the disease was transmitted by transfer of anti-MPO antibodies or anti-MPO–specific splenocytes. The most frequently affected organs in this disease are the kidneys and the lungs. Necrotizing and crescentic glomerulonephritis can be revealed by rapidly progressive renal failure, but kidney injury can be more slowly progressive and lead to end-stage renal disease without major extrarenal manifestations. The most frequent pulmonary manifestation is diffuse alveolar hemorrhage, but some patients may present with chronic interstitial fibrosis leading to respiratory failure. General signs such as fever and weight loss, muscular and articular symptoms, peripheral neuropathy, and cutaneous involvement may also reveal the disease. Although the relapse rate is quite low after induction of remission, 5-year mortality is 25%, with even higher mortality rates in older patients (> 65 years old), or those with significant kidney dysfunction. Iatrogenic causes (particularly infections) are an important cause of deaths in these vulnerable patients. Future studies are warranted to determine the optimal maintenance immunosuppressive regimen to minimize side effects of immunosuppression.

Reappraisal of Renal Arteritis in ANCA-Associated Vasculitis: Clinical Characteristics, Pathology, and Outcome

2021 ◽  
pp. ASN.2020071074
Author(s):  
Idris Boudhabhay ◽  
Florence Delestre ◽  
Guillaume Coutance ◽  
Viviane Gnemmi ◽  
Thomas Quéméneur ◽  
...  
Keyword(s):  
Risk Score ◽  
Renal Involvement ◽  
External Validation ◽  
Multivariable Analysis ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Prior History ◽  
Clinicopathologic Characteristics ◽  
Anca Associated Vasculitis ◽  
Poor Outcomes ◽  
Stage Renal Disease

Background Renal involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. Methods In a multicenter cohort of AAV patients with renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis and to retrospectively analyze their prognostic value. Results We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, prior history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with end-stage renal disease. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESRD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. Conclusions Our findings suggest that AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.

Microparticles Expressing Myeloperoxidase and Complement C3a and C5a as Markers of Renal Involvement in Antineutrophil Cytoplasmic Antibody–associated Vasculitis

2019 ◽  
Vol 47 (5) ◽  
pp. 714-721 ◽  
Author(s):  
Aleksandra Antovic ◽  
Fariborz Mobarrez ◽  
Milena Manojlovic ◽  
Nida Soutari ◽  
Victoria De Porta Baggemar ◽  
...  
Keyword(s):  
Disease Activity ◽  
Renal Involvement ◽  
Serum Levels ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Birmingham Vasculitis Activity Score ◽  
Complement Components ◽  
Anca Associated Vasculitis ◽  
Terminal Complement ◽  
Active Disease

Objective.To investigate expression of terminal complement components C3a and C5a on circulating myeloperoxidase (MPO)-positive microparticles (MPO+MP) in relation to disease activity and renal involvement in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods.Forty-six clinically well-characterized patients with AAV and 23 age- and sex-matched healthy controls were included. The concentration of MPO+MP expressing C3a and C5a was analyzed from citrate plasma by flow cytometry. Serum levels of C3a and C5a were determined using commercial ELISA. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS). Among patients, 23 had active disease with BVAS ≥ 2 and 14 patients had active renal flares.Results.AAV patients had significantly increased expression of C3a and C5a on MPO+MP compared to controls (both p < 0.0001). When the group of patients with active AAV was divided according to the presence of renal activity, the concentration of MPO+MP expressing C3a and C5a was significantly higher in patients with renal involvement compared to patients with nonrenal disease and controls (p < 0.05 and p < 0.01, respectively). The serum levels of C3a were significantly decreased (p < 0.01) in the renal subgroup, while there were no changes in serum levels of C5a comparing the renal and nonrenal groups. There was significant correlation between the disease activity measured by BVAS and the levels of C3a and C5a expressed on MPO+MP.Conclusion.Determination of C3a and C5a on MPO+MP might be considered as a novel biomarker of renal involvement in patients with AAV and may be of importance in the pathogenetic process.

scholarly journals Systematic Scoring of Tubular Injury Patterns Reveals Interplay between Distinct Tubular and Glomerular Lesions in ANCA-Associated Glomerulonephritis

2021 ◽  
Vol 10 (12) ◽  
pp. 2682
Author(s):  
Samy Hakroush ◽  
Désirée Tampe ◽  
Peter Korsten ◽  
Philipp Ströbel ◽  
Björn Tampe
Keyword(s):  
Medical Center ◽  
Renal Involvement ◽  
Disease Onset ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Small Vessel Vasculitis ◽  
Glomerular Sclerosis ◽  
Tubular Injury ◽  
Injury Patterns ◽  
Renal Biopsies ◽  
Glomerular Lesions

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA). Acute tubular injury with the presence of tubulitis was previously reported to be of prognostic value in ANCA glomerulonephritis (GN). In particular, distinct tubular injury lesions were associated with the deterioration of kidney function at AAV disease onset, as well as renal resistance to treatment, and higher risk of progression to composite outcome in patients with AAV. To expand our knowledge regarding distinct tubular lesions in AAV, we aimed to describe acute tubular injury patterns in association with glomerular lesions in ANCA GN by systematic histological scoring. Methods: A total number of 48 renal biopsies with confirmed renal involvement of AAV admitted to the University Medical Center Göttingen from 2015 to 2020 were retrospectively examined. By systematic scoring of tubular injury lesions, the association between clinical parameters, laboratory markers, and histopathological findings was explored. Results: We have shown that cellular casts in renal biopsies were frequently observed in the majority of cases with ANCA GN. Furthermore, we showed that tubular epithelial simplification with dilatation correlated with MPA and MPO subtypes, C3c hypocomplementemia, severe renal involvement, and uACR. Red blood cell (RBC) casts were associated with increased levels of C-reactive protein (CRP), leukocyturia, and hematuria. Finally, we found that hyaline casts were associated with an increased fraction of glomeruli with global glomerular sclerosis. Conclusions: Acute tubular injury patterns were correlated with active ANCA GN, whereas tubular injury lesions reflecting the later stages of kidney disease correlated with chronic glomerular lesions. These results suggest an interplay between different renal compartments.

scholarly journals Cholemic Nephropathy as Cause of Acute and Chronic Kidney Disease. Update on an Under-Diagnosed Disease

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1200
Author(s):  
Francesca Tinti ◽  
Ilaria Umbro ◽  
Mariadomenica D’Alessandro ◽  
Silvia Lai ◽  
Manuela Merli ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Prolonged Exposure ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Diagnosis And Treatment ◽  
Prognostic Scores ◽  
Renal Outcome ◽  
Clinical Settings ◽  
Severe Hyperbilirubinemia

Cholemic nephropathy (CN) is a recognized cause of acute kidney injury (AKI) in patients with severe hyperbilirubinemia (sHyb) and jaundice. Pathophysiological mechanisms of CN are not completely understood, but it seems caused both by direct toxicity of cholephiles and bile casts formation in nephrons enhanced by prolonged exposure to sHyb, particularly in the presence of promoting factors, as highlighted by a literature reviewed and by personal experience. The aim of our update is to retrace CN in its pathophysiology, risk factors, diagnosis and treatment, underlining the role of sHyb, promoting factors, and CN-AKI diagnostic criteria in the different clinical settings associated with this often-concealed disease. Our purpose is to focus on clinical manifestation of CN, exploring the possible transition to CKD. Cholemic nephropathy is an overlooked clinical entity that enters differential diagnosis with other causes of AKI. Early diagnosis and treatment are essential because renal injury could be fully reversible as rapidly as bilirubin levels are reduced. In conclusion, our proposal is to introduce an alert for considering CN in diagnostic and prognostic scores that include bilirubin and/or creatinine with acute renal involvement, with the aim of early diagnosis and treatment of sHyb to reduce the burden on renal outcome.

MO303URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS IN ANCA-ASSOCIATED VASCULITIS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Samy Hakroush ◽  
Björn Tampe
Keyword(s):  
Kidney Function ◽  
Renal Involvement ◽  
Disease Onset ◽  
Clinical Importance ◽  
Kidney Injury ◽  
Histopathological Diagnosis ◽  
Intermediate Risk ◽  
Creatinine Ratio ◽  
Anca Associated Vasculitis ◽  
Renal Biopsies

Abstract Background and Aims Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as it can cause acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We have previously reported that elevated urinary albumin-to-creatinine ratio (uACR) correlates with rapid deterioration of kidney function in ANCA GN. Therefore, we here aimed to describe the association between proteinuric findings and histopathological diagnosis of necrotizing and crescentic ANCA GN in 50 urinary samples at admission and corresponding renal biopsies of patients with AAV. Method A total number of 50 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study. Results Renal involvement of AAV revealed variable proteinuria ranging from low-range to nephrotic syndromes, however most patients presented with subnephrotic proteinuria predominated by albumin (uACR). Severely increased uACR levels &gt;300 mg/g correlated with reduction of normal glomeruli (P&lt;0.001), attributed to increased glomerular crescents (P&lt;0.001) and necrosis (P=0.008). By contrast, no such association was observed for global sclerotic glomeruli (P=0.58), revealing that uACR reflects necrotizing and crescentic ANCA GN rather than adaptive glomerular hyperfilitration in chronic sclerosing stage. These findings were additionnaly bolstered by histopathological subgrouping and ARRS: patients with uACR levels &gt;300 mg/g were classified either into Berden’s crescentic class (P=0.002) or ANCA renal risk score (ARRS) high/intermediate risk (P=0.003). No association between uACR levels and extrarenal manifestation of AAV disease could be observered, suggesting that uACR levels reflected specific renal involvement with ANCA GN and further confirmed by survival analysis for cumulative incidence of RRT during the short-term course of disease. In summary, uACR measurements at admission were associated with renal biopsy findings thereafter. Levels of uACR &gt;300 mg/g were more frequently observed in necrotizing and crescentic ANCA GN with classification either into Berden’s crescentic class or ARRS high/intermediate risk and specific for renal involvement in AAV. Conclusion Early identification of patients who mostly benefit from aggressive immunosuppressive therapy is of clinical importance. Our observation that uACR levels at disease onset predict necrotizing and crescentic ANCA GN requires further investigation for therapeutic decision especially in patients with severe deterioration of kidney function.

scholarly journals Urinary Biomarkers in Relapsing Antineutrophil Cytoplasmic Antibody-associated Vasculitis

2013 ◽  
Vol 40 (5) ◽  
pp. 674-683 ◽  
Author(s):  
Jason G. Lieberthal ◽  
David Cuthbertson ◽  
Simon Carette ◽  
Gary S. Hoffman ◽  
Nader A. Khalidi ◽  
...  
Keyword(s):  
Renal Disease ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Fold Increase ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Likelihood Ratios ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Disease States ◽  
Kidney Injury Molecule 1

Objective.Glomerulonephritis (GN) is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of renal involvement are imperfect. We investigated 4 urinary proteins as markers of active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL).Methods.Patients with active renal AAV (n = 20), active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were identified within a longitudinal cohort. Urinary biomarker concentrations (by ELISA) were normalized for urine creatinine. Marker levels during active AAV were compared to baseline remission levels (from 1–4 visits) for each patient. Areas under receiver-operating characteristic curves (AUC), sensitivities, specificities, and likelihood ratios (LR) comparing disease states were calculated.Results.Baseline biomarker levels varied among patients. All 4 markers increased during renal flares (p < 0.05). MCP-1 discriminated best between active renal disease and remission: a 1.3-fold increase in MCP-1 had 94% sensitivity and 89% specificity for active renal disease (AUC = 0.93, positive LR 8.5, negative LR 0.07). Increased MCP-1 also characterized 50% of apparently nonrenal flares. Change in AGP, KIM-1, or NGAL showed more modest ability to distinguish active renal disease from remission (AUC 0.71–0.75). Hematuria was noted in 83% of active renal episodes, but also 43% of nonrenal flares and 25% of remission samples.Conclusion.Either urinary MCP-1 is not specific for GN in AAV, or it identifies early GN not detected by standard assessment and thus has potential to improve care. A followup study with kidney biopsy as the gold standard is needed.

Plasma Exchange Treatment in Rapidly Progressive Glomerulonephritis Associated with Antineutrophil Cytoplasmic Autoantibodies

1992 ◽  
Vol 15 (3) ◽  
pp. 181-184 ◽  
Author(s):  
G.M. Frascà ◽  
N.G. Zoumparidis ◽  
L.C. Borgnino ◽  
L. Neri ◽  
A. Vangelista ◽  
...  
Keyword(s):  
Renal Function ◽  
Disease Activity ◽  
Plasma Exchange ◽  
Systemic Disease ◽  
Rapidly Progressive Glomerulonephritis ◽  
Risk Of Death ◽  
Systemic Symptoms ◽  
Stage Renal Disease ◽  
End Stage ◽  
Antineutrophil Cytoplasmic Autoantibodies

This study reports on 12 patients with acute renal failure due to biopsy-proven rapidly progressive glomerulonephritis and signs of systemic disease in whom antineutrophil cytoplasmic autoantibodies (ANCA) were detected by indirect immunofluorescence (IIF) on alcohol-fixed neutrophils and assessed in serial determinations by ELISA. The diagnosis was: Wegener's granulomatosis in nine patients who showed a diffuse cytoplasmic pattern at IIF (c-ANCA), and microscopic polyarteritis in three where a perinuclear pattern (pANCA) was seen. All patients underwent a course of plasma exchange - PE - (3-10 sessions per patient) associated with steroids and cyclophosphamide. The ANCA titer dropped steeply during PE in all cases and was followed by disappearance of systemic symptoms and renal function improvement within four weeks. After a follow-up period of 50 ± 31.2 months all patients were alive without signs of disease activity; ten had stable renal function, with serum creatinine 1.8 ± 0.7 mg/dl; two had entered regular dialysis treatment after 44 and 82 months. Our results suggest that the rapid removal of ANCA by means of PE can help control disease activity and reduce the risk of death or end-stage renal disease.

scholarly journals Proliferative glomerulonephritis and mantle cell lymphoma: a rare association

2021 ◽  
Vol 14 (2) ◽  
pp. e238153
Author(s):  
Bilel Mhedhbi ◽  
Soumaya Chargui ◽  
Amel Harzallah ◽  
Rim Goucha
Keyword(s):  
Acute Kidney Injury ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Oral Prednisone ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Proteinase 3 ◽  
Rare Association ◽  
Mantle Cell

Renal involvement in mantle cell lymphoma (MCL) is rare. We present the case of a man followed for MCL presented with acute kidney injury and positive antineutrophil cytoplasmic antibody (ANCA) type anti proteinase 3 (PR3). He was treated as for a rapidly progressing glomerulonephritis with cyclophosphamide and methylprednisolone followed by oral prednisone. Renal biopsy revealed diffuse endocapillary proliferation and segmental extracapillary proliferation in four glomeruli. Immunohistochemistry confirmed the renal invasion of lymphomatous cells. He started improving his renal function shortly after starting treatment. The coexistence of renal MCL infiltration, extracapillary proliferation and ANCA positive is exceptional.

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