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

Coppo, Rosanna; D’Arrigo, Graziella; Tripepi, Giovanni; Russo, María Luisa; Roberts, Ian S.; Bellur, Shubha S.; Cattran, Daniel C.; Cook, Terence; Feehally, John; Tesař, Vladimı́r; Maixnerová, Dita; Peruzzi, Licia; Amore, Alessandro; Lundberg, Sigrid; Palma, Anna Maria Di; Gesualdo, Loreto; Emma, Francesco; Rollino, Cristiana; Praga, Manuel; Biancone, Luigi; Pani, Antonello; Feriozzi, Sandro; Polci, Rosaria; Barratt, Jonathan; Vecchio, Lucia Del; Locatelli, Francesco; Pierucci, Alessandro; Çalışkan, Yaşar; Perkowska‐Ptasińska, Agnieszka; Durlik, Magdalena; Moggia, Elisabetta; Ballarín, J.; Wetzels, Jack F.M.; Goumenos, Dimitris; Papasotiriou, Marios; Gales̃ić, Kres̆imir; Toric, Luka; Papagianni, Αikaterini; Stangou, Μaria; Benozzi, Luisa; Cusinato, Stefano; Berg, Ulla; Topaloğlu, Rezan; Maggio, Milena; Ots-Rosenberg, Mai; D’Amico, Marco; Geddes, Colin C.; Balafa, Olga; Quaglia, Marco; Cravero, Raffaella; Cirami, Calogero; Fellström, Bengt; Floege, Jürgen; Egido, Jesús; Mallamaci, Francesca; Zoccali, Carmine

doi:10.1093/ndt/gfy302

Cited by 75 publications

(56 citation statements)

References 30 publications

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“…The MEST‐C components that showed significant association with the prognosis of native IgAN varied in previous studies, and the implication of the Oxford classification has remained debatable . A meta‐analysis and a recent validation study showed that the M, S, T, and C scores were important predictive parameters for the prognosis of native kidney IgAN even after the consideration of bias from immunosuppressive treatment . Furthermore, the T score was most prominently associated with kidney function loss in native IgAN, suggesting that final tubular injury may be the chronic consequence of intraglomerular disease activity.…”

Section: Discussionmentioning

confidence: 99%

Clinical importance of the updated Oxford classification in allograft IgA nephropathy

Park

Baek

et al. 2019

American Journal of Transplantation

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With the recent update to the Oxford classification for allograft IgA nephropathy (IgAN), additional investigations on the clinical significance of the updated components are warranted. We performed a retrospective cohort study at two tertiary hospitals. Kidney transplant recipients diagnosed with allograft IgAN were included in the study after additional review by specialized pathologists. We applied the updated Oxford classification and determined the MEST-C scores of the patients. The main study outcome was death-censored graft failure within 10 years after the establishment of allograft IgAN diagnosis and was assessed using the Cox regression analysis.Three hundred thirty-three allograft IgAN patients were reviewed: 100 patients with confirmed native IgAN and 233 patients with other, clinical, or unknown primary causes for end-stage renal disease (ESRD). The updated Oxford classification for allograft IgAN demonstrated prognostic value for graft failure, and patients with multiple MEST-C components had worse outcomes. M, E, S, and C were significantly associated with the prognosis of recurred IgAN and T was the only independent prognostic parameter for allograft IgAN without confirmed native IgAN. Therefore, we suggest reporting MEST-C scores in allograft biopsies and careful interpretation of the results according to the primary cause of ESRD. K E Y W O R D Sclinical research/practice, glomerular biology and disease, graft survival, kidney (allograft) function/dysfunction, kidney disease: immune/inflammatory, kidney transplantation/ nephrology, pathology/histopathology, recurrent disease

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Section: Discussionmentioning

confidence: 99%

Clinical importance of the updated Oxford classification in allograft IgA nephropathy

Park

Baek

et al. 2019

American Journal of Transplantation

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“…In the present study, tubular atrophy/interstitial fibrosis in the participants with low levels of hemoglobin was severer than that in the participants with high levels of hemoglobin, and hemoglobin levels correlated negatively to the grade of tubular atrophy/interstitial fibrosis (male: r = −0.15, p < 0.001; female: r = −0.12, p < 0.001). Tubular atrophy/interstitial fibrosis has been demonstrated to be associated with progression of IgAN [37][38][39]. Therefore, low levels of hemoglobin may indicate worse tubular atrophy/interstitial fibrosis that was associated with IgAN progression.…”

Section: Discussionmentioning

confidence: 99%

The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases

Zhu¹,

Liu²,

Yu³

et al. 2020

Am J Nephrol

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Aim: To investigate the relationship between hemoglobin levels and the progression of IgA nephropathy (IgAN). Methods: In a two-center cohort of 1,828 cases with biopsy-proven IgAN, we examined the association of hemoglobin levels with the primary outcome of a composite of all-cause mortality or kidney failure defined as a 40% decline in eGFR, or ESKD (defined as eGFR <15 mL/min/1.73 m 2 or need for kidney replacement therapy including hemodialysis, peritoneal dialysis, or kidney transplantation), or the outcome of kidney failure, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. Results: At baseline, mean age, eGFR, and hemoglobin levels were 33.75 ± 11.03 years, 99.70 ± 30.40 mL/min/1.73 m 2 , and 123.47 ± 18.36 g/L, respectively. During a median of approximately 7-year follow-up, 183 cases reached the composite outcome. After adjustment for demographic and IgAN-specific covariates and treatments, a lower quartile of hemoglobin was nonlinearly associated with an increased risk of the primary outcome or kidney failure in the Cox proportional hazards models (primary outcome: HR for quartile 3 vs. 4, 1.37; 95% CI, 0.83-2.25; HR for quartile 2 vs. 4, 1.18; 95% CI, 0.68-2.07; HR for quartile 1 vs. 4, 1.91; 95% CI, 1.15-3.17; kidney failure: HR for quartile 3 vs. 4, 1.39; 95% CI, 0.84-2.31; HR for quartile 2 vs. 4, 1.20; 95% CI, 0.68-2.11; HR for quartile 1 vs. 4, 1.83; 95% CI, 1.09-3.07) in the fully adjusted model. Then, hemo-Bin Zhu and Wen-hua Liu contributed equally to this work.

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“…The long-term outcome of pediatric IgAN in the VALIGA cohort was investigated in a recent study updating the database and prolonging the follow-up from 4.7 to 7.0 years [13]. At 20 years from renal biopsy, 20% of the 174 children developed 50% eGFR loss or ESRD.…”

Section: Clinical Features Of Children and Young Subjects With Igan Imentioning

confidence: 99%

“…The Japanese reports on an increase in T lesions in children in whom the decision for renal biopsy was delayed or when CS were not used [25, 26] have further stressed the attitude for Europe to treat progressive IgAN in children with aggressive therapy [18, 27, 28]. In Europe, the results of the long-term follow-up of the VALIGA study [13] clearly indicated that when T lesions develop, the disease enters a relentless phase of progression, and that M1, S1, and also C lesions in untreated cases can have an impact on disease outcome decades later in children as well as in adults.…”

Section: Treatment Of Pediatric Igan In Europementioning

confidence: 99%

Pediatric IgA Nephropathy in Europe

Coppo

2019

Kidney Dis

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Background: In Europe IgA nephropathy (IgAN) is detected in 20% of children with glomerular diseases diagnosed by renal biopsy. The outcome during childhood is generally good, but progression in the long-term follow-up may occur in about 20% of children after 20 years. Summary: In Europe, urine screening programs are not active, and there is variability in the policy to perform renal biopsies in oligo-symptomatic children. Hence, a suitable observational approach to pediatric IgAN is offered by the VALIGA study which included 174 children aged < 18 years from 13 European countries followed over a median of 4.4 (2.5–7.5) years. Renal pathology lesions were centrally scored according to the Oxford Classification of IgAN (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T; crescents, C [MEST-C]). Children had renal biopsy mostly with normal estimated glomerular filtration rate (eGFR) and moderate proteinuria of a median of 0.84 g/day/1.73 m² (< 0.30 g/day/1.73 m² in 30% of the cases). Children showed M1 in 21.8%, E1 in 13.8%, S1 in 42.5%, T1–2 in 6.3%, and C1 in 14.9%. The survival at the combined endpoint of 50% eGFR decrease or end-stage renal disease at 15 years was 94%. The slow progression rate and the limited number of cases progressing to the combined endpoint (6.4%) did not allow the detection of a predictive value of the MEST-C score. Moreover, the predictive value of clinical and pathological features was likely blunted by the use of corticosteroid/immunosuppressive treatment (CS/IS) in 50% of the cases. The survival tree analysis also proved that children < 16 years old with IgAN without mesangial hypercellularity (M0) and well preserved eGFR (> 90 mL/min/1.73 m²) had a high probability of proteinuria remission during follow-up. Moreover, in this subgroup of children, the benefits of CS/IS therapy reached statistical significance. In Europe, the use of CS/IS treatment in IgAN is still a debated issue, but most children tend to be treated more commonly than adults with CS/IS. A recent uncontrolled study reports a favorable outcome in European children with IgAN and very active acute forms of IgAN with improvement in eGFR and reduction in proteinuria. Key Messages: In Europe, children with IgAN have a favorable prognosis in the short term, and this may be due also to the frequently adopted CS/IS therapy, particularly with acute and active pathological features. The risk of progression over decades of follow-up remains an unsolved problem which needs to be addressed by controlling subtle chronic pathogenetic factors which work in children as well as in adult cases of IgAN.

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

Cited by 75 publications

References 30 publications

Clinical importance of the updated Oxford classification in allograft IgA nephropathy

Clinical importance of the updated Oxford classification in allograft IgA nephropathy

The Association of Low Hemoglobin Levels with IgA Nephropathy Progression: A Two-Center Cohort Study of 1,828 Cases

Pediatric IgA Nephropathy in Europe

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