Repeat renal biopsy improves the Oxford classification-based prediction of immunoglobulin A nephropathy outcome

2018 ◽  
Vol 35 (7) ◽  
pp. 1179-1186 ◽  
Author(s):  
Perrine Jullien ◽  
Blandine Laurent ◽  
François Berthoux ◽  
Ingrid Masson ◽  
Miriana Dinic ◽  
...  
Keyword(s):  
Clinical Data ◽  
Immunoglobulin A ◽  
Kidney Tissue ◽  
Patient Treatment ◽  
Histological Evaluation ◽  
Prognostic Impact ◽  
Oxford Classification ◽  
Cox Models ◽  
Renal Biopsies ◽  
The Oxford Classification

Abstract Background The prognosis of IgA nephropathy (IgAN) is very heterogeneous. Predicting the nature and the rate of the disease progression is crucial for refining patient treatment. The aim of this study was to evaluate the prognostic impact of an Oxford classification-based repeat kidney tissue evaluation to predict end-stage renal disease (ESRD). Methods Patients with biopsy-proven primary IgAN who underwent two renal biopsies at our centre were analyzed retrospectively. Renal biopsies were scored by two pathologists blinded to the clinical data and according to the updated Oxford classification. Cox models were generated to evaluate the prognostic impact considering the Oxford classification elementary lesions from the first (Model 1) or the second (Model 2) biopsy, adjusted on clinical data at time of reevaluation. The prognostic impacts of the dynamic evolution of each elementary lesion between biopsies were also assessed through univariate and multivariate evaluation. Results A total of 168 adult patients were included, with a median follow-up duration of 18 (range 11–24) years. The second biopsy was performed either systematically (n = 112) of for-cause (n = 56), after a median time of 5.4 years. The prognostic performances of Model 2 (second biopsy) were significantly better than Model 1 (first biopsy, analysis of deviance P < 0.0001). The dynamic changes of C and T lesions were significantly associated with the progression toward ESRD after adjustment on variables from Model 2. Conclusion Both static and dynamic Oxford-based histological evaluation offered by a repeat biopsy improves the prediction of ESRD in patients with IgAN.

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 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 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 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 &lt; 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.

scholarly journals Evaluation of the Oxford classification in immunoglobulin A vasculitis with nephritis: a cohort study and meta-analysis

2020 ◽  
Author(s):  
Bingxin Yu ◽  
Sufang Shi ◽  
Wanyin Hou ◽  
Lijun Liu ◽  
Jicheng Lv ◽  
...  
Keyword(s):  
Cohort Study ◽  
Interstitial Fibrosis ◽  
Meta Analysis ◽  
Immunoglobulin A ◽  
Renal Outcome ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
The Oxford Classification ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Similarities in clinicopathological presentations in immunoglobulin A (IgA) nephropathy and IgA vasculitis with nephritis (IgAVN) raise the question of the utility of the Oxford classification in the latter. The aim of this study was to evaluate the Oxford classification in IgAVN. Methods We conducted a retrospective cohort study and meta-analysis following systematic searching of the MEDLINE and Excerpta Medica Database (EMBASE) databases between January 2009 and September 2019. We modeled the association of 30 and 50% decline in estimated glomerular filtration rate or end-stage renal disease with pathologic lesions of the Oxford classification including mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C). Results were pooled using random-effects meta-analysis. Results The cohort study included 132 patients, and only T lesion was an independently risk factor in IgAVN. The meta-analysis yielded six retrospective studies with 721 patients and 139 endpoints. In multivariate model, T lesion was significantly associated with renal outcome (hazard ratio = 2.45, P = 0.007). M and C lesions could not predict renal outcome without evidence of heterogeneity. E and S lesions could not predict renal outcome with evidence of heterogeneity (I2 = 66.6%; P = 0.01, and I2 = 65.8%; P = 0.03, respectively). Subgroup analysis showed that the possible reasons to the heterogeneity were from usage of immunosuppressant, sample size and follow-up time. Conclusions The study suggests that the Oxford classification could not be fully validated in IgAVN. Higher portion of immunosuppressant especially before renal biopsy might be the main confounder for the predictive value of Oxford classification in IgAVN.

scholarly journals Extracapillary proliferation scoring correlates with renal outcome and contributes to stratification in adult patients with immunoglobulin A nephropathy

2019 ◽  
Author(s):  
Jhonny L Moreno ◽  
Lida M Rodas ◽  
Juliana Draibe ◽  
Xavier Fulladosa ◽  
Montserrat Gomá ◽  
...  
Keyword(s):  
Renal Function ◽  
Interstitial Fibrosis ◽  
Severe Disease ◽  
Immunoglobulin A ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Renal Survival ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
Renal Biopsies

Abstract Background The revised Oxford classification of diagnostic renal biopsies has been proposed to aid in the prediction of renal outcome. We aimed to validate the histological crescents and interstitial fibrosis and tubular atrophy (IFTA) subgrouping, and to investigate the additional value of the proportion of crescents (CatPE) in the prediction of renal outcome. Methods Data were retrospectively collected over 10 years, from the time of diagnosis, by systematic review of medical records from 90 patients with renal biopsies recruited to cohorts from two hospitals in Spain. Patients were classified into three groups for the analysis: CatPE >25% (C2), CatPE <25% (C1) and without this type of lesion (C0). The end point was renal survival defined by either >50% reduction in glomerular filtrate rate or end-stage renal disease. Results Renal survival at 5 years was 90% in group C0, 81% in group C1 and 31% in group C2 (P = 0.013). The presence of >25% crescents in the sample was associated with more severe disease when compared with <25%, as demonstrated by more interstitial fibrotic change and by lower estimated glomerular filtration rate at diagnosis, as well as worse renal function at 2 and 5 years. At the time of diagnosis and at 24 months, the group with IFTA >50% had poorer renal function compared with the other groups. Conclusions We have confirmed the predictive value for renal survival of the revised Oxford classification in a two-centre study. We found worse renal outcome in patients with severe tubulointerstitial fibrosis and atrophy. Patients with extracapillary lesions >25% and IFTA >50% had a worse renal prognosis due to more severe kidney injury. These results contribute to patient stratification in immunoglobulin A nephropathy for therapeutic, epidemiological and basic research.

Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort

2018 ◽  
Vol 34 (10) ◽  
pp. 1681-1690 ◽  
Author(s):  
Shubha S Bellur ◽  
Ian S D Roberts ◽  
Stéphan Troyanov ◽  
Virginie Royal ◽  
Rosanna Coppo ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Study Cohort ◽  
Immunoglobulin A Nephropathy ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
Tubulointerstitial Lesions ◽  
The Oxford Classification ◽  
The Impact

Abstract Background The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.

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