scholarly journals Evaluation of Clinical and Pathological Characteristics of Patients with IgA Nephropathy Based on Oxford Classification System: Should Crescents be Included?

2017 ◽  
Vol 15 (1) ◽  
pp. 10-15
Author(s):  
Sibel Ersan ◽  
Omur Gokmen Sevindik ◽  
Caner Cavdar ◽  
Sibel Ada ◽  
Aykut Sifil ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Classification System ◽  
Clinical Course ◽  
Immunoglobulin A ◽  
Classification Systems ◽  
Oxford Classification ◽  
Crescent Formation ◽  
Pathological Characteristics ◽  
The Oxford Classification

Abstract Introduction. None of the classification systems in immunoglobulin A (IgA) nephropathy has been widely agreed or implemented by clinicians or pathologists. In order to meet this need, "Oxford Classification System", which is highly reproducible and predictive for clinical course, was developed in 2009. In the present study, we investigated clinical and pathological characteristics of patients with IgA nephropathy based on current classification and the predictivity of crescent presence on prognosis. Methods. The study comprised 40 patients with diagnosis of primary IgA nephropathy on renal biopsy. The biopsy findings and follow-up parameters of patients were retrospectively re-evaluated. Pathological findings were examined based on the Oxford classification system. The presence of crescent formation in the specimens was noted. Results. The presence of crescent formation was predictive of poor prognosis regarding the glomerular filtration rate (eGFR), the level of proteinuria, and mean arterial pressure (MAP). Conclusion: Considering the importance of crescent formation in prediction of the clinical course and need for immunosuppressive therapy, it is suggested that crescent presence can be included in this classification system.

Relationship between complement deposition and the Oxford classification score and their combined effects on renal outcome in immunoglobulin A nephropathy

2019 ◽  
Vol 35 (12) ◽  
pp. 2103-2137 ◽  
Author(s):  
Seohyun Park ◽  
Hyung Woo Kim ◽  
Jung Tak Park ◽  
Tae Ik Chang ◽  
Ea Wha Kang ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Primary Endpoint ◽  
Immunoglobulin A ◽  
Renal Outcome ◽  
Oxford Classification ◽  
Classification Score ◽  
Hazard Ratios ◽  
The Oxford Classification ◽  
Complement Deposition

Abstract Background Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function. Methods We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up. Results Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1–2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1–2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1–2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone. Conclusions Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.

scholarly journals Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update

2018 ◽  
Vol 35 (6) ◽  
pp. 1002-1009 ◽  
Author(s):  
Rosanna Coppo ◽  
Graziella D'Arrigo ◽  
Giovanni Tripepi ◽  
Maria Luisa Russo ◽  
Ian S D Roberts ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Validation Study ◽  
Kidney Failure ◽  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Immunoglobulin A Nephropathy ◽  
Oxford Classification ◽  
The Oxford Classification

Abstract Background It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. Methods In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1–10.8)]. Results In this extended analysis, M1, S1 and T1–T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). Conclusion Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

Immunoglobulin A nephropathy diagnosis

2018 ◽  
Author(s):  
Kar Neng Lai ◽  
Sydney C. W. Tang
Keyword(s):  
Immunoglobulin A ◽  
Oxford Classification ◽  
Crescent Formation ◽  
Skin Changes ◽  
Population Average ◽  
Serum Iga ◽  
Necrotizing Glomerulonephritis ◽  
The Oxford Classification ◽  
Schonlein Purpura ◽  
Urine And Serum

The defining histological hallmark of immunoglobulin A (IgA) nephropathy is the presence of IgA in the mesangium as the sole or dominant immunoreactant. Light microscopy appearances vary very widely. The most common appearance is mesangial cell proliferation and an increase in mesangial matrix. However, this is not diagnostic in the absence of immunohistology. Focal segmental proliferative or necrotizing glomerulonephritis may be seen in ‘vasculitic’ disease with or without the skin changes of Henoch–Schönlein purpura. Extracapillary proliferation and crescent formation may occur. Occasionally florid haematuria may cause renal failure through acute tubular injury. Most commonly the disease is slowly evolving and focal or global sclerosis and tubulointerstitial scarring develop. The Oxford classification scheme may give some prognostic weight to these changes. There are no reliable serological or urine tests for the disease. Although average levels of serum IgA are above the population average this is not diagnostically useful in individual patients. Promising biomarkers in urine and serum are under investigation.

scholarly journals Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy

2019 ◽  
Vol 44 (5) ◽  
pp. 928-941
Author(s):  
Shu-Wei Duan ◽  
Yan Mei ◽  
Jian Liu ◽  
Pu Chen ◽  
Ping Li ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Prognostic Value ◽  
Cox Regression ◽  
Hierarchical Classification ◽  
Information Criterion ◽  
Classification Systems ◽  
Oxford Classification ◽  
Clinical Indicators ◽  
Pathological Classification ◽  
The Oxford Classification

Background/Aims: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. Methods: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). Results: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21–0.74; Oxford classification 0.48, 95% CI 0.28–0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23–0.92; Oxford classification 0.59, 95% CI 0.10–0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. Conclusions: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.

scholarly journals Clinical Significance of Crescent Formation in IgA Nephropathy – a Multicenter Validation Study

2019 ◽  
Vol 44 (1) ◽  
pp. 22-32 ◽  
Author(s):  
Sehoon  Park ◽  
Chung Hee  Baek ◽  
Su-Kil  Park ◽  
Hee Gyung  Kang ◽  
Hye Sun  Hyun ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Validation Study ◽  
Cox Regression ◽  
Immunoglobulin A ◽  
Renal Outcome ◽  
Oxford Classification ◽  
Crescent Formation ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
The Oxford Classification

Background/Aims: Additional validation study was warranted to confirm the clinical significance of C score, which was recently added to the Oxford classification for immunoglobulin A nephropathy (IgAN). Methods: We performed a multicenter retrospective cohort study in four hospitals in Korea. Patients who had biopsied glomeruli less than eight or inadequate follow-up information were excluded. Clinicopathologic parameters, including the degree of cellular or fibrocellular crescents, were collected and included in multivariable models for Cox regression analysis. The main outcome was a composite renal outcome, defined as a merge of progression to end-stage renal disease (ESRD) and halving of estimated glomerular filtration rate (eGFR) from baseline. Results: Among included 3,380 biopsy-confirmed IgAN patients, there were 664 (19.6%) patients with C1 and 60 (1.8%) patients with C2 scores in the study population. Although C0 and C1 patients shared similar baseline characteristics, C2 patients frequently had more clinicopathologic risk factors for poor prognosis of IgAN. Both C1 [adjusted HR 1.33 (1.11-1.58), P=0.002] and C2 [adjusted HR 2.24 (1.46-3.43), P< 0.001] scores were associated with an increased risk of the composite outcome. C2 was a strong predictive parameter associated with both progression to ESRD and halving of eGFR, whereas C1 was mainly associated with the increased risk of halving of eGFR. Notably, the proportion of crescent showed a linear association with the risk of adverse renal outcome. Conclusion: The C score in the Oxford classification is a valid predictive parameter for IgAN prognosis. Additional clinical attention is necessary for IgAN patients with identified cellular or fibrocellular crescents.

scholarly journals The Role of Complement Component C3 Activation in the Clinical Presentation and Prognosis of IgA Nephropathy—A National Study in Children

2021 ◽  
Vol 10 (19) ◽  
pp. 4405
Author(s):  
Małgorzata Mizerska-Wasiak ◽  
Agnieszka Such-Gruchot ◽  
Karolina Cichoń-Kawa ◽  
Agnieszka Turczyn ◽  
Jadwiga Małdyk ◽  
...  
Keyword(s):  
Kidney Biopsy ◽  
Clinical Presentation ◽  
Immunofluorescence Microscopy ◽  
Clinical Course ◽  
National Study ◽  
Oxford Classification ◽  
Complement Component C3 ◽  
The Oxford Classification

The aim of the study was to evaluate the influence of the intensity of mesangial C3 deposits in kidney biopsy and the serum C3 level on the clinical course and outcomes of IgAN in children. The study included 148 children from the Polish Pediatric IgAN Registry, diagnosed based on kidney biopsy. Proteinuria, creatinine, IgA, C3 were evaluated twice in the study group, at baseline and the end of follow-up. Kidney biopsy was categorized using the Oxford classification, with a calculation of the MEST-C score. The intensity of IgA and C3 deposits were rated from 0 to +4 in immunofluorescence microscopy. The intensity of mesangial C3 > +1 deposits in kidney biopsy has an effect on renal survival with normal GFR in children with IgAN. A reduced serum C3 level has not been a prognostic factor in children but perhaps this finding should be confirmed in a larger group of children.

scholarly journals Characteristics of patients with coexisting DNAJB9-associated fibrillary glomerulonephritis and IgA nephropathy

2020 ◽  
Author(s):  
Samar M Said ◽  
Alejandro Best Rocha ◽  
Anthony M Valeri ◽  
Mohamad Sandid ◽  
Anhisekh Sinha Ray ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Immunoglobulin A ◽  
Renal Survival ◽  
Hepatitis C Infection ◽  
Clinicopathologic Characteristics ◽  
Fibrillary Glomerulonephritis ◽  
Kaplan Meier ◽  
Dense Deposits ◽  
End Stage

Abstract Background Coexistence of fibrillary glomerulonephritis (FGN) and immunoglobulin A (IgA) nephropathy (IgAN) in the same kidney biopsy (FGN–IgAN) is rare, and the clinicopathologic characteristics and outcome of this dual glomerulopathy are unknown. Methods In this study, 20 patients with FGN–IgAN were studied and their characteristics were compared with 40 FGN and 40 IgAN control patients. Results Concurrent IgAN was present in 1.8% of 847 consecutive FGN cases and was the second most common concurrent glomerulopathy after diabetic nephropathy. FGN–IgAN patients were overwhelmingly White (94%) and contrary to FGN patients were predominantly (60%) males. Compared with IgAN patients, FGN–IgAN patients were older, had higher proteinuria, a higher incidence of renal insufficiency, and a lower incidence of microhematuria and gross hematuria at diagnosis. Six (30%) patients had malignancy, autoimmune disease or hepatitis C infection, but none had a secondary cause of IgAN or clinical features of Henoch–Schonlein purpura. Histologically, all cases exhibited smudgy glomerular staining for immunoglobulin G and DnaJ homolog subfamily B member 9 (DNAJB9) with corresponding fibrillary deposits and granular mesangial staining for IgA with corresponding mesangial granular electron-dense deposits. On follow-up (median 27 months), 10 of 18 (56%) FGN–IgAN patients progressed to end-stage kidney disease (ESKD), including 5 who subsequently died. Serum creatinine at diagnosis was a poor predictor of renal survival. The proportion of patients reaching ESKD or died was higher in FGN–IgAN than in IgAN. The median Kaplan–Meier ESKD-free survival time was 44 months for FGN–IgAN, which was shorter than IgAN (unable to compute, P = 0.013) and FGN (107 months, P = 0.048). Conclusions FGN–IgAN is very rare, with clinical presentation and demographics closer to FGN than IgAN. Prognosis is guarded with a median renal survival of 3.6 years. The diagnosis of this dual glomerulopathy requires careful evaluation of immunofluorescence findings, and electron microscopy or DNAJB9 immunohistochemistry.

The Oxford Classification of IgA Nephropathy: A Retrospective Analysis

2011 ◽  
Vol 34 (5) ◽  
pp. 435-444 ◽  
Author(s):  
Timothy Yau ◽  
Stephen M. Korbet ◽  
Melvin M. Schwartz ◽  
David J. Cimbaluk
Keyword(s):  
Retrospective Analysis ◽  
Iga Nephropathy ◽  
Oxford Classification ◽  
The Oxford Classification
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