scholarly journals The Association of the Oxford Classification Score with Longitudinal Estimated Glomerular Filtration Rate Decline in Patients with Immunoglobulin A Nephropathy: A Mixed-Method Study

2021 ◽  
Vol Volume 14 ◽  
pp. 2655-2663
Author(s):  
Ricong Xu ◽  
Zhijian Li ◽  
Tao Cao ◽  
Yi Xu ◽  
Ying Liao ◽  
...  
Keyword(s):  
Mixed Method ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Immunoglobulin A ◽  
Mixed Method Study ◽  
Immunoglobulin A Nephropathy ◽  
Oxford Classification ◽  
Classification Score ◽  
Glomerular Filtration Rate Decline ◽  
The Oxford Classification

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.

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.

scholarly journals Renal Outcomes in Brazilian Patients with Immunoglobulin A Nephropathy and Cellular Crescentic Lesions

2020 ◽  
Vol 45 (3) ◽  
pp. 431-441
Author(s):  
Precil Diego Miranda de Menezes Neves ◽  
Rafaela Bezerra Brito Pinheiro ◽  
Cristiane Bitencourt Dias ◽  
Luis Yu ◽  
Leonardo de Abreu Testagrossa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Renal Biopsy ◽  
Biopsy Specimen ◽  
Immunoglobulin A ◽  
Composite Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Oxford Classification ◽  
Cox Regression Analysis ◽  
Independent Risk Factors ◽  
The Impact

Background and Aim: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy. The Oxford classification was recently updated to include crescents as markers of poor prognosis. The aim of this study was to evaluate the impact of cellular crescents on the prognosis of patients with IgAN in Brazil. Methods: This was a single-centre retrospective analysis of medical records and renal biopsies in patients with IgAN. The renal biopsy findings were classified according to the revised Oxford classification: mesangial hypercellularity, endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy or interstitial fibrosis (T), and crescent formation (C). We evaluated a composite outcome (progression to end-stage renal disease or creatinine doubling). We performed analyses between the patients with crescents in the renal biopsy specimen (C1/C2 group) and those without such crescents (C0 group). Results: We evaluated 111 patients, of whom 72 (65.0%) were women, 80 (72.0%) self-identified as White, 73 (65.6%) were hypertensive, and 95 (85.6%) had haematuria. The distribution of patients according to cellular crescentic lesions was: C0, 80 (72%); C1, 27 (24.4%); C2, 4 (3.6%). The composite outcome was observed in 33 (29.72%) of the 111 patients. In comparison with the C0 group, the C1/C2 group had higher proportions of patients with hypertension (p = 0.04), haematuria (p = 0.03), worse serum creatinine (p = 0.0007), and worse estimated glomerular filtration rate (p = 0.0007). The C1/C2 group also had higher proportions of patients in whom the biopsy specimen was classified as E1 (p = 0.009), S1 (p = 0.001), or T1/T2 (p = 0.03), In addition, the mean follow-up period was shorter in the C1/C2 group (p < 0.0001). Furthermore, the composite outcome was observed in a greater proportion of patients and in a shorter length of time in the C1/C2 group than in the C0 group (p = 0.002 and p = 0.0014, respectively). In a Cox regression analysis, the independent risk factors for the composite outcome had Oxford classifications of S1, T1/T2, and C1/C2. Conclusion: Oxford classification findings of S1, T1/T2, or C1/C2 were independent risk factors for the composite outcome, corroborating previous studies.

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.

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