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

Jullien, Perrine; Laurent, B.; Berthoux, F; Masson, Ingrid; Dinic, M.; Claisse, Guillaume; Thibaudin, Damien; Mariat, Christophe; Alamartine, Éric; Maillard, Nicolas

doi:10.1093/ndt/gfy341

Cited by 18 publications

(20 citation statements)

References 34 publications

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“…However, the lack of other robust biomarkers emphasizes the importance of kidney biopsies for prognostic information. It has been suggested that repeated kidney biopsies may provide clinicians with more accurate and up-to-date prognostic predictions [ 38 ]. Recent improvements in prognostic models, combined with developments in treatment alternatives, stress the importance of performing a kidney biopsy in patients with suspected IgAN [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Utilizing the MEST score for prognostic staging in IgA nephropathy

et al. 2022

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Background The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. Methods A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). Results The mean follow-up time was 16.5 years (range 0.2–28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. Conclusions Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.

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Section: Discussionmentioning

confidence: 99%

Utilizing the MEST score for prognostic staging in IgA nephropathy

et al. 2022

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“… 30 Some studies of Oxford Classification scores on repeated biopsies showed that T and S lesions did not improve after immunosuppressive treatments; on the contrary, deterioration appeared to be very common. 25 , 31 , 32 These phenomena suggest that T2 and S1 lesions might reflect poor responsiveness or even unresponsiveness to currently available treatments. Further studies with repeated biopsies are needed to determine whether these lesions are potentially treatable or only cause progressive chronic damage.…”

Section: Discussionmentioning

confidence: 99%

“… 25 Another study found no statistically significant changes between the first and second biopsy with respect to C lesions (16% vs 11%). 32 Nevertheless, these studies did not analyze the severity of the crescents (ie, C1 or C2), and there were more patients with C1 lesions than C2 lesions. In our study, C1 and C2 accounted for 48.6% and 8.9%, respectively, which suggests that the persistence or deterioration of C lesions in previous studies can probably be attributed to C2 lesions.…”

Section: Discussionmentioning

confidence: 99%

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

Cao

et al. 2021

IJGM

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Introduction The Oxford Classification score, which predicts renal outcomes for immunoglobulin A nephropathy (IgAN), is widely used in clinical practice. Nevertheless, the relationship between these markers and longitudinal changes in renal function are poorly understood. Methods This was a population-based retrospective cohort study of 280 adults with biopsy-proven primary IgAN from 2011 to 2018. We used generalized additive mixed models to control for traditional kidney disease risk factors to analyze the associations between Oxford Classification MEST-C scores (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T; crescents, C) and longitudinal changes in the estimated glomerular filtration rate (eGFR) after renal biopsy. Results The median eGFR was 78.2 mL/min/1.73 m 2 at baseline, and then it decreased on average by 1.3 mL/min/1.73 m 2 per year in the entire cohort. In adjusted models, compared with patients without relative lesions, the presence of T > 50% (T2) (−5.7; 95% confidence interval [CI], −9.5 to −2.0 mL/min/1.73m 2 per year) was associated with the fastest eGFR decline. S present (S1) (−2.9; 95% CI, −4.6 to −1.1 mL/min/1.73m 2 per year) and C > 25% glomeruli (C2) (−3.4; 95% CI, −6.4 to −0.5 mL/min/1.73m 2 per year) also demonstrated steeper eGFR declines. However, we found no association between M > 0.5 (M1), E present (E1), T 26%–50% (T1), and C present ≥ 1 glomerulus (C1), and progressive eGFR decline (p > 0.05). Conclusion The Oxford Classification scores, S1, T2, and C2, were independently associated with the longitudinal decreases in renal function in patients with IgAN. These findings suggested therapies targeted at improving early damage to these lesions might be essential to delay renal progression.

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“…It must be emphasized that these lesions are not static and, either spontaneously or with treatment, may change over time. Several repeat biopsy studies [75,76,77,78,79] have consistently shown the reversal of active lesions (endocapillary hypercellularity, fibrinoid necrosis and crescents, mesangial hypercellularity) following IS therapy. As such, active lesions (M, E, C) might resolve or progress to chronic lesions (S, T).…”

Section: Transitioning From Pathogenesis Of Iga Nephropathy To Promentioning

confidence: 99%

Has The Time Arrived to Refine The Indications of Immunosuppressive Therapy and Prognosis in IgA Nephropathy?

Obrișcă

Sinescu

Ismail

et al. 2019

JCM

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Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease worldwide and a leading cause of end-stage renal disease. Particularly challenging to the clinician is the early identification of patients at high risk of progression, an estimation of the decline in renal function, and the selection of only those that would benefit from additional immunosuppressive therapies. Nevertheless, the pathway to a better prognostication and to the development of targeted therapies in IgAN has been paved by recent understanding of the genetic and molecular basis of this disease. Merging the data from the Oxford Classification validation studies and prospective treatment studies has suggested that a disease-stratifying algorithm would be appropriate for disease management, although it awaits validation in a prospective setting. The emergence of potential noninvasive biomarkers may assist traditional markers (proteinuria, hematuria) in monitoring disease activity and treatment response. The recent landmark trials of IgAN treatment (STOP-IgAN and TESTING trials) have suggested that the risks associated with immunosuppressive therapy outweigh the benefits, which may shift the treatment paradigm of this disease. While awaiting the approval of the first therapies for IgAN, more targeted and less toxic immunotherapies are warranted. Accordingly, the targeting of complement activation, the modulation of mucosal immunity, the antagonism of B-cell activating factors, and proteasomal inhibition are currently being evaluated in pilot studies for IgAN treatment.

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

Cited by 18 publications

References 34 publications

Utilizing the MEST score for prognostic staging in IgA nephropathy

Utilizing the MEST score for prognostic staging in IgA nephropathy

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

Has The Time Arrived to Refine The Indications of Immunosuppressive Therapy and Prognosis in IgA Nephropathy?

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