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 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.

Propylthiouracil-induced Antineutrophil Cytoplasmic Antibody (ANCA)-associated Renal Vasculitis Versus Primary ANCA-associated Renal Vasculitis: A Comparative Study

2012 ◽  
Vol 39 (3) ◽  
pp. 558-563 ◽  
Author(s):  
YONG-XI CHEN ◽  
WEN ZHANG ◽  
XIAO-NONG CHEN ◽  
HAI-JIN YU ◽  
LI-YAN NI ◽  
...  
Keyword(s):  
Estimated Glomerular Filtration Rate ◽  
Interstitial Fibrosis ◽  
Renal Involvement ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Good Prognosis ◽  
Small Vessel Vasculitis ◽  
Renal Survival ◽  
Tubular Atrophy ◽  
Renal Vasculitis ◽  
Immunological Abnormalities

Objective.Renal involvement is frequently present in primary antineutrophil cytoplasmic antibody-associated small-vessel vasculitis (AAV) as well as propylthiouracil (PTU)-induced AAV. We analyzed the characteristics of patients with PTU-induced AAV with renal involvement and investigated the differences of the 2 diseases.Methods.Thirty-six patients with PTU-induced AAV, diagnosed from 1997 to 2010, were enrolled for study. Their data were compared with those of 174 patients with primary AAV diagnosed at the same time. Renal involvement was present in all patients.Results.There was a prominent proportion of young women with PTU-induced AAV (p < 0.01). They had lower levels of proteinuria and serum creatinine and higher estimated glomerular filtration rate (p < 0.01, p < 0.01, and p < 0.01, respectively). Clinical immunological abnormalities were less severe in patients with PTU-induced AAV. Patients with PTU-induced AAV had less organ involvement and lower Birmingham Vasculitis Assessment Score than patients with primary AAV (p < 0.01). Renal biopsies showed a lower proportion of glomeruli with crescents (p < 0.01). Interstitial inflammation was less severe in patients with PTU-induced AAV (p < 0.05). Similarly, interstitial fibrosis and tubular atrophy were less severe in patients with PTU-induced AAV (p < 0.01, p < 0.05, respectively). Renal survival and total survival were better in patients with PTU-associated vasculitis (p < 0.05, p = 0.01).Conclusion.Clinical and histopathological abnormalities were less severe in patients with PTU-induced AAV and most of them had a good prognosis.

Clinical and Pathological Features of Microscopic Polyangiitis in 20 Children

2014 ◽  
Vol 41 (8) ◽  
pp. 1712-1719 ◽  
Author(s):  
Liangzhong Sun ◽  
Haiyan Wang ◽  
Xiaoyun Jiang ◽  
Ying Mo ◽  
Zhihui Yue ◽  
...  
Keyword(s):  
Microscopic Polyangiitis ◽  
Renal Involvement ◽  
Disease Onset ◽  
Antithyroid Drug ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Pulse Therapy ◽  
Pathological Features ◽  
The Central Nervous System ◽  
Age Range ◽  
Clinical And Pathological Features

Objective.To explore the clinical and pathological features of microscopic polyangiitis (MPA) in children.Methods.A retrospective analysis was performed of patients with pediatric MPA in our hospital over 10 years.Results.Data for 20 patients were collected; 16 patients had primary MPA (4 boys, 12 girls), with a median age of 8.9 years at the time of disease onset; 4 patients, all female, had antithyroid drug (ATD)-associated MPA, with an age range of 12.5 to 16.2 years at the time of disease onset. All patients exhibited renal involvement. Renal biopsies were performed in 14 patients. Fibrinoid exudation and necrosis of the glomerular capillaries were observed in all biopsy specimens. Crescents and scleroses were noted in 92.9% and 85.7% of these cases, respectively. The most frequent extrarenal organs involved were lungs, followed by the central nervous system (CNS), skin, and digestive system. Ninety percent of patients were positive for perinuclear antineutrophil cytoplasmic antibody, 94.1% were positive for myeloperoxidase, and 88.2% were positive for both. Forty-five percent of the patients had received steroid plus cyclophosphamide (CTX) pulse therapy for more than 3 months, and varying degrees of remission had been achieved in 88.9% of the patients.Conclusion.Both primary and ATD-associated MPA showed a female predisposition. Renal involvement was the most frequently observed condition, followed by involvement of lungs. CNS involvement was not rare in these pediatric patients. The efficacy of steroid plus CTX as induction therapy was evident in these patients.

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 Onset age is a risk factor for refractory pediatric IgA vasculitis: a retrospective cohort study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Chun-Hua Liao ◽  
Melody Tsai ◽  
Yao-Hsu Yang ◽  
Bor-Luen Chiang ◽  
Li-Chieh Wang
Keyword(s):  
Complete Remission ◽  
Medical Center ◽  
Renal Involvement ◽  
Laboratory Data ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Joint Involvement ◽  
Refractory Disease ◽  
Iga Vasculitis ◽  
Onset Age

Abstract Background Though outcome differences between children and adults with immunoglobulin A vasculitis (IgAV) has been well documented, it remains unclear if disease features in pediatric IgAV patients vary with onset age. We aimed to explore clinical features and prognosis of pediatric IgAV stratified by onset age. Methods We retrospectively reviewed records of patients under 18 years old diagnosed with IgAV from January 1999 to December 2018 in one tertiary medical center in Taiwan. Patients were grouped by onset age: ≤ 6 years old, 6–12 years old (> 6, ≤ 12), and 12–18 years old (> 12, < 18). Demographics, laboratory data, incidence of gastrointestinal, renal, and joint involvement, corticosteroid dependence, recurrence, and refractory disease were analyzed. Recurrence was defined as disease flare-up after complete remission and discontinuation of all medications for at least 3 months. Corticosteroid dependence was defined by more than 6 weeks of daily oral corticosteroid intake. Refractory disease was defined as not achieving complete remission 6 months after disease onset. Statistical analysis was performed using R software (v3.6.0). Results There were 484 IgAV patients, with an onset age of 6.10 (4.72–8.58) (median (IQR)) years old. There were 234 (48.3%) patients ≤6 years old, 210 (43.4%) 6–12 years old, and 40 (8.3%) 12–18 years old. One hundred and thirty (26.9%) patients had renal involvement, which was more frequent in older children (≤ 6 years old, 18.4%; 6–12 years old, 31.0%; 12–18 years old, 55.0%; p <  0.001). There were 361 patients (74.6%) with joint involvement; younger children were affected more frequently (≤ 6 years old, 82.1%; 6–12 years old, 71.9%; 12–18 years old, 45.0%; p <  0.001). Gastrointestinal involvement was present in 311 (64.3%) patients, showing no difference among age groups. There were 46 patients (9.5%) with recurrent IgA vasculitis, 136 (28.1%) with corticosteroid dependent and 76 (15.7%) with refractory disease. Corticosteroid dependence and refractory disease occurred more frequently as onset age increased (p <  0.001). Conclusion Pediatric IgAV with different onset ages are associated with distinct clinical manifestations and outcomes. The risk of developing corticosteroid dependence, refractory disease and renal involvement increased with onset age.

scholarly journals Pathology of Antineutrophil Cytoplasmic Antibody–Associated Pulmonary and Renal Disease

2017 ◽  
Vol 141 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Maxwell L. Smith
Keyword(s):  
Differential Diagnosis ◽  
Renal Disease ◽  
Clinical Laboratory ◽  
Tissue Injury ◽  
Renal Involvement ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Small Vessel Vasculitis ◽  
Antibody Testing ◽  
Anca Associated Vasculitis ◽  
Histopathologic Diagnosis

Context.—Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis commonly presents with pulmonary and renal involvement that may present diagnostic challenges. Objectives.—To highlight the updates in the classification of small vessel vasculitis, present the patterns of pulmonary and renal pathology in which ANCA-associated vasculitis is included in the differential diagnosis, analyze the screening and specific antineutrophil cytoplasmic antibody testing methods in the clinical laboratory, compare and contrast the 3 major ANCA-associated vasculitis diseases, and review the pathophysiologic mechanisms of tissue injury in this setting. Data Sources.—Data are derived from published literature and clinical experience. Conclusions.—Although rare, ANCA-associated vasculitis diseases are often considered in the differential diagnosis of many pathologic patterns of pulmonary and renal disease. Histopathologic diagnosis of specific entities in this context nearly always requires correlation of the pathology with clinical and serologic data.

scholarly journals AB0400 URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITISIN ANCA-ASSOCIATED VASCULITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1228-1228
Author(s):  
S. Hakroush ◽  
B. Tampe
Keyword(s):  
Kidney Function ◽  
Renal Involvement ◽  
Disease Onset ◽  
Urinary Albumin ◽  
Histopathological Diagnosis ◽  
Creatinine Ratio ◽  
Short Term ◽  
Anca Associated Vasculitis ◽  
Renal Biopsies ◽  
Severe Deterioration

Background: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.Objectives: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.Methods: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. Severe deterioration of kidney function requiring RRT within 30 days after admission was associated with elevated levels of nonselective proteinuria, mostly attributed to albuminuria (uACR). Because we have previously shown that histologically confirmed ANCA GN with glomerular crescents and necrosis is associated with AKI and requirement of RRT during short-term disease course and elevated uACR levels were equally associated with AKI and requirement of RRT during the short-term course after disease onset, we next analyzed the association between uACR measurements at admission and histopathological findings within renal biopsies performed thereafter. Severely increased uACR levels >300 mg/g correlated with reduction of normal glomeruli, attributed to increased glomerular crescents and necrosis. By contrast, no such association was observed for global sclerotic glomeruli, revealing that uACR reflects crescentic ANCA GN rather than adaptive glomerular hyperfilitration in chronic sclerosing stage. Since uACR levels could reflect both, either a specific renal involvement with necrotizing and crescentic ANCA GN or severity of systemic AAV disease, we next correlated uACR levels assessed at admission with extrarenal disease manifestation. We observed no association between uACR levels and extrarenal manifestation of AAV disease including pulmonary hemorrhage, skin involvement and BVAS assessment, suggesting that uACR levels reflected specific renal involvement in AAV. These observations were further confirmed by survival analysis for cumulative incidence of RRT during the short-term course of disease.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.Disclosure of Interests:None declared

Eosinophile Granulomatose mit Polyangiitis (eGPA) in der Niere: Glomerulonephritis und interstitielle Nephritis

2021 ◽  
Vol 3 (1) ◽  
pp. 12-14
Author(s):  
Sibylle von Vietinghoff
Keyword(s):  
Renal Biopsy ◽  
Membranous Nephropathy ◽  
Late Onset ◽  
Renal Involvement ◽  
Acute Interstitial Nephritis ◽  
Consensus Conference ◽  
Alveolar Haemorrhage ◽  
Small Vessel Vasculitis ◽  
Eosinophilic Granulomatosis With Polyangiitis ◽  
Granulomatose Mit Polyangiitis

<b>Objective:</b> Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small-vessel vasculitis characterized by asthma, hypereosinophilia and ANCA positivity in 40% of patients. Renal involvement is rare and poorly described, leading to this renal biopsy-proven based study in a large EGPA cohort. <b>Methods:</b> We conducted a retrospective multicentre study including patients fulfilling the 1990 ACR criteria and/or the 2012 revised Chapel Hill Consensus Conference criteria for EGPA and/or the modified criteria of the MIRRA trial, with biopsy-proven nephropathy. <b>Results:</b> Sixty-three patients [27 women, median age 60 years (18–83)] were included. Renal disease was present at vasculitis diagnosis in 54 patients (86%). ANCA were positive in 53 cases (84%) with anti-MPO specificity in 44 (83%). All patients had late-onset asthma. Peripheral neuropathy was present in 29 cases (46%), alveolar haemorrhage in 10 (16%). The most common renal presentation was acute renal failure (75%). Renal biopsy revealed pauci-immune necrotizing GN in 49 cases (78%). Membranous nephropathy (10%) and membranoproliferative GN (3%) were mostly observed in ANCA-negative patients. Pure acute interstitial nephritis was found in six cases (10%); important interstitial inflammation was observed in 28 (44%). All patients received steroids with adjunctive immunosuppression in 54 cases (86%). After a median follow-up of 51 months (1–296), 58 patients (92%) were alive, nine (14%) were on chronic dialysis and two (3%) had undergone kidney transplantation. <b>Conclusion:</b> Necrotizing pauci-immune GN is the most common renal presentation in ANCA-positive EGPA. ANCA-negative patients had frequent atypical renal presentation with other glomerulopathies such as membranous nephropathy. An important eosinophilic interstitial infiltration was observed in almost 50% of cases.

scholarly journals Anca-associated crescentic glomerulonephritis in a child with isolated renal involvement

2019 ◽  
Vol 41 (2) ◽  
pp. 293-295
Author(s):  
Mehtap Ezel Çelakıl ◽  
Burcu Bozkaya Yücel ◽  
Umay Kiraz Özod ◽  
Kenan Bek
Keyword(s):  
Crescentic Glomerulonephritis ◽  
Renal Involvement ◽  
Immunosuppressive Treatment ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Normal Serum ◽  
Laboratory Findings ◽  
Elevated Creatinine ◽  
Systemic Symptoms ◽  
Mild Clinical Presentation ◽  
Normal Serum Creatinine

ABSTRACT Pauci-immune glomerulonephritis (GN) is more common in elderly people compared to children and the etiology is not completely understood yet. Antineutrophil cytoplasmic antibody (ANCA) positivity occurs in 80% of the patients. We report a case of a 7-year-old girl who presented with malaise and mildly elevated creatinine diagnosed as ANCA-associated pauci-immune crescentic glomerulonephritis with crescents in 20 of 25 glomeruli (80%). Of these 20 crescents, 12 were cellular, 4 fibrocellular, and 4 globally sclerotic. She did not have purpura, arthritis, or systemic symptoms and she responded well to initial immunosuppressive treatment despite relatively severe histopathology. The patient was given three pulses of intravenous methylprednisolone (30 mg/kg on alternate days) initially and continued with cyclophosphamide (CYC; 2 mg/kg per day) orally for 3 months with prednisone (1 mg/kg per day). In one month, remission was achieved with normal serum creatinine and prednisone was gradually tapered. The case of this child with a relatively rare pediatric disease emphasizes the importance of early and aggressive immunosuppressive treatment in patients with renal-limited ANCA-associated pauci-immune crescentic GN even if with a mild clinical presentation. As in our patient, clinical and laboratory findings might not always exactly reflect the severity of renal histopathology and thus kidney biopsy is mandatory in such children to guide the clinical management and predict prognosis.

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