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

Author

Coppo, R., D'Arrigo, G., Tripepi, G., Russo, M. L., Roberts, I. S. D., Bellur, S., Cattran, D., Cook, T. H., Feehally, J., Tesar, V., Maixnerova, D., Peruzzi, L., Amore, A., Lundberg, S., Di Palma, A. M., Gesualdo, L., Emma, F., Rollino, C., Praga, M., Biancone, L., Pani, A., Feriozzi, S., Polci, R., Barratt, J., Del Vecchio, L., Locatelli, F., Pierucci, A., Caliskan, Y., Perkowska-Ptasinska, A., Durlik, M., Moggia, E., Ballarin, J. C., Wetzels, J. F. M., Goumenos, D., Papasotiriou, M., Galesic, K., Toric, L., Papagianni, A., Stangou, M., Benozzi, L., Cusinato, S., Berg, U., Topaloglu, R., Maggio, M., Ots-Rosenberg, M., D'Amico, M., Geddes, C., Balafa, O., Quaglia, M., Cravero, R., Cirami, C. L., Fellstrom, B., Floege, J., Egido, J., Mallamaci, F., Zoccali, C., Fuiano, L., Beltrame, G., Camilla, R., Segoloni, G., Colla, L., Angioi, A., Piras, L., Cancarini, G., Ravera, S., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Sever, M., Kilicaslan, I., Peters, H., Carvalho, F., Da Costa Ferreira, A. C., Wiecek, A., Magistroni, R., Bilginer, Y., Giacchino, F., Papastirou, M., Siamopoulos, K., Galliani, M., Stratta, P., Bergia, R., Salvadori, M., Cirami, L., Kloster Smerud, H., Ferrario, F., Stellato, T., Martin, C., Eitner, F., Rauen, T., Lupo, A., Bernich, P., Mene, P., Morosetti, M., Van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Gutierrez, E., Asunis, A. M., Tardanico, R., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Akiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., and Internal Medicine

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Adolescent, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, Kidney, Nephropathy, Cohort Studies, 03 medical and health sciences, Glomerulonephritis, 0302 clinical medicine, renal biopsy, Interquartile range, IgA nephropathy, progression, risk factors, Child, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate, Glomerulonephritis, IGA, Humans, Prognosis, Medicine, Endocapillary hypercellularity, IGA, Transplantation, medicine.diagnostic_test, business.industry, medicine.disease, medicine.anatomical_structure, Renal pathology, Nephrology, Cohort, Renal biopsy, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
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 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.

Published
2020
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2. Quantifying duration of proteinuria remission and association with clinical outcome in IgA nephropathy

Author

Canney, M., Barbour, S. J., Zheng, Y., Coppo, R., Zhang, H., Liu, Z. -H., Matsuzaki, K., Suzuki, Y., Katafuchi, R., Reich, H. N., Cattran, D., Russo, M. L., Troyanov, S., Cook, H. T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A. M., Gutierrez, E., Asunis, A. M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Cook, T., Alpers, C., Feehally, J., Berthoux, F., Bonsib, S., D'Agati, V., D'Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, C. -H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Anesthesiology, Pathology, Graduate School, ACS - Heart failure & arrhythmias, and ACS - Atherosclerosis & ischemic syndromes

Subjects
Male, Time Factors, glomerular disease, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, 0302 clinical medicine, Outcome Assessment, Health Care, Clinical endpoint, Medicine, Clinical Epidemiology, Proteinuria, medicine.diagnostic_test, Remission Induction, Hazard ratio, IgA nephropathy, General Medicine, Middle Aged, end stage kidney disease, epidemiology and outcomes, proteinuria, renal function decline, renal pathology, 3. Good health, Renal pathology, Nephrology, Disease Progression, Female, medicine.symptom, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Nephropathy, 03 medical and health sciences, Internal medicine, Biopsy, Humans, Proportional Hazards Models, Retrospective Studies, business.industry, Surrogate endpoint, Glomerulonephritis, IGA, medicine.disease, Confidence interval, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Kidney Failure, Chronic, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract

Contains fulltext : 232930.pdf (Publisher’s version ) (Closed access) BACKGROUND: On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS: In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to

Published
2021

3. 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

Author

Bellur, S. S., Roberts, I. S. D., Troyanov, S., Royal, V., Coppo, R., Cook, H. T., Cattran, D., Terroba, Y. A., Asunis, A. M., Bajema, I., Bertoni, E., Bruijn, J. A., Cannata-Ortiz, P., Casartelli, D., Di Palma, A. M., Ferrario, F., Fortunato, M., Furci, L., Gakiopoulou, H., Ljubanovic, D. G., Giannakakis, K., Goma, M., Grone, H. -J., Gutierrez, E., Haider, S. A., Honsova, E., Ioachim, E., Karkoszka, H., Kipgen, D., Maldyk, J., Mazzucco, G., Orhan, D., Ozluk, Y., Pantzaki, A., Perkowska-Ptasinska, A., Riispere, Z., Soderberg, M. P., Steenbergen, E., Stoppacciaro, A., Von Feilitzen, B. S., Tardanico, R., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., Feehally, J., Barratt, J., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Grinyo, J. M., Fulladosa, X., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., and Kilicaslan, I.

Subjects
medicine.medical_specialty, IgA nephropathy, immunosuppression, kidney biopsy, Oxford classification, proteinuria, medicine.medical_treatment, Biopsy, 030232 urology & nephrology, Disease, 030204 cardiovascular system & hematology, Lesion, 03 medical and health sciences, 0302 clinical medicine, Glomerulonephritis, Models, Internal medicine, medicine, Humans, Endocapillary hypercellularity, Clinical significance, IGA, Retrospective Studies, Observer Variation, Transplantation, Models, Statistical, Proteinuria, medicine.diagnostic_test, business.industry, Patient Selection, Oxford classification, Reproducibility of Results, Glomerulonephritis, IGA, Immunosuppression, Statistical, Prognosis, Nephrology, proteinuria, Glomerular Filtration Rate, Immunosuppressive Agents, Cohort, medicine.symptom, business
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.

Published
2019

4. Evaluating a New International Risk-Prediction Tool in IgA Nephropathy

Author

Barbour, Sean J. Coppo, Rosanna Zhang, Hong Liu, Zhi-Hong and Suzuki, Yusuke Matsuzaki, Keiichi Katafuchi, Ritsuko Er, Lee Espino-Hernandez, Gabriela Kim, S. Joseph Reich, Heather N. Feehally, John Cattran, Daniel C. Russo, M. L. and Troyanov, S. Cook, H. T. Roberts, I. Tesar, V. and Maixnerova, D. Lundberg, S. Gesualdo, L. Emma, F. and Fuiano, L. Beltrame, G. Rollino, C. Amore, A. Camilla, R. Peruzzi, L. Praga, M. Feriozzi, S. Polci, R. and Segoloni, G. Colla, L. Pani, A. Piras, D. Angioi, A. and Cancarini, G. Ravera, S. Durlik, M. Moggia, E. Ballarin, J. Di Giulio, S. Pugliese, F. Serriello, I. Caliskan, Y. and Sever, M. Kilicaslan, I. Locatelli, F. Del Vecchio, L. and Wetzels, J. F. M. Peters, H. Berg, U. Carvalho, F. and da Costa Ferreira, A. C. Maggio, M. Wiecek, A. and Ots-Rosenberg, M. Magistroni, R. Topaloglu, R. Bilginer, Y. and D'Amico, M. Stangou, M. Giacchino, F. Goumenos, D. and Kalliakmani, P. Gerolymos, M. Galesic, K. Geddes, C. and Siamopoulos, K. Balafa, O. Galliani, M. Stratta, P. and Quaglia, M. Bergia, R. Cravero, R. Salvadori, M. Cirami, L. Fellstrorn, B. Smerud, H. Kloster Ferrario, F. and Stellato, T. Egido, J. Martin, C. Floege, J. Eitner, F. and Lupo, A. Bernich, P. Mene, R. Morosetti, M. van Kooten, C. Rabelink, T. Reinders, M. E. J. Boria Grinyo, J. M. Cusinato, S. Benozzi, L. Savoldi, S. Licata, C. and Mizerska-Wasiak, M. Martina, G. Messuerotti, A. Dal Canton, A. Esposito, C. Migotto, C. Triolo, G. Mariano, F. and Pozzi, C. Boero, R. Bellur, S. Mazzucco, G. Giannakakis, C. Honsova, E. Sundelin, B. Di Palma, A. M. Ferrario, F. and Gutierrez, E. Asunis, A. M. Barratt, J. Tardanico, R. and Perkowska-Ptasinska, A. Arce Terroba, J. Fortunato, M. and Pantzaki, A. Ozluk, Y. Steenbergen, E. Soderberg, M. and Riispere, Z. Furci, L. Orhan, D. Kipgen, D. Casartelli, D. Ljubanovic, D. Galesic Gakiopoulou, H. Bertoni, E. and Cannata Ortiz, P. Karkoszka, H. Groene, H. J. Stoppacciaro, A. Bajema, I. Bruijn, J. Fulladosa Oliveras, X. Maldyk, J. Loachim, E. Bavbek, N. Cook, T. Troyanov, S. and Alpers, C. Amore, A. Barratt, J. Berthoux, F. Bonsib, S. and Bruijn, J. D'Agati, V D'Amico, G. Emancipator, S. and Emmal, F. Ferrario, F. Fervenza, F. Florquin, S. Fogo, A. Geddes, C. Groene, H. Haas, M. Hill, P. Hogg, R. and Hsu, S. Hunley, T. Hladunewich Jennette, C. Joh, K. and Julian, B. Kawamura, T. Lai, F. Leung, C. Li, L. and Li, P. Liu, Z. Massat, A. Mackinnon, B. Mezzano, S. and Schena, F. Tomino, Y. Walker, P. Wang, H. Weening, J. and Yoshikawa, N. Zeng, Cai-Hong Shi, Sufang Nogi, C. and Suzuki, H. Koike, K. Hirano, K. Kawamura, T. Yokoo, T. and Hanai, M. Fukami, K. Takahashi, K. Yuzawa, Y. Niwa, M. Yasuda, Y. Maruyama, S. Ichikawa, D. Suzuki, T. and Shirai, S. Fukuda, A. Fujimoto, S. Trimarchi, H. Int IgA Nephropathy Network

Abstract

ImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. ObjectiveTo derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and ParticipantsWe derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and MeasuresCox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R-D(2) measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. ResultsThe study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R-D(2) (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and RelevanceIn this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

Published
2019

5. Evaluating a New International Risk-Prediction Tool in IgA Nephropathy

Author

Barbour, Sean J., Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Katafuchi, Ritsuko, Er, Lee, Espino-Hernandez, Gabriela, Kim, S. Joseph, Reich, Heather N., Feehally, John, Cattran, Daniel C., Russo, M. L., Troyanov, S., Cook, H. T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellström, Bengt, Smerud, Hilde Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, R., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A. M., Gutierrez, E., Asunis, A. M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Ljubanovic, D. Galesic, Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Loachim, E., Bavbek, N., Cook, T., Alpers, C., Berthoux, F., Bonsib, S., D'Agati, V, D'Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, Cai-Hong, Shi, Sufang, Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., Trimarchi, H., Barbour, Sean J., Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Katafuchi, Ritsuko, Er, Lee, Espino-Hernandez, Gabriela, Kim, S. Joseph, Reich, Heather N., Feehally, John, Cattran, Daniel C., Russo, M. L., Troyanov, S., Cook, H. T., Roberts, I., Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellström, Bengt, Smerud, Hilde Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, R., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A. M., Gutierrez, E., Asunis, A. M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Arce Terroba, J., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Ljubanovic, D. Galesic, Gakiopoulou, H., Bertoni, E., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Loachim, E., Bavbek, N., Cook, T., Alpers, C., Berthoux, F., Bonsib, S., D'Agati, V, D'Amico, G., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Groene, H., Haas, M., Hill, P., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Weening, J., Yoshikawa, N., Zeng, Cai-Hong, Shi, Sufang, Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fukuda, A., Fujimoto, S., and Trimarchi, H.

Abstract

Importance Although IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. Objective To derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and Participants We derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and Measures Cox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R2D measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. Results The study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R2D (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (ΔC, 0.04; 95% CI, 0.03-0.04 and ΔC, 0.03

Published
2019
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6. Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments

Author

Coppo, Rosanna, Troyanov, Stéphan, Bellur, Shubha, Cattran, Daniel, Cook, H. Terence, Feehally, John, Roberts, Ian S.D., Morando, Laura, Camilla, Roberta, Tesar, Vladimir, Lunberg, Sigrid, Gesualdo, Loreto, Emma, Francesco, Rollino, Cristiana, Amore, Alessandro, Praga, Manuel, Feriozzi, Sandro, Segoloni, Giuseppe, Pani, Antonello, Cancarini, Giovanni, Durlik, Magalena, Moggia, Elisabetta, Mazzucco, Gianna, Giannakakis, Costantinos, Honsova, Eva, Sundelin, B. Brigitta, Palma, Anna Maria Di, Ferrario, Franco, Gutierrez, Eduardo, Asunis, Anna Maria, Barratt, Jonathan, Tardanico, Regina, Perkowska-Ptasinska, Agnieszka, Maixnerova, D., Lundberg, S., Fuiano, L., Beltrame, G., Peruzzi, L., Polci, R., Colla, L., Angioi, A., Piras, D., Ravera, S., Ballarin, J., Di Giulio, S., Pugliese, F., Caliskan, Y., Locatelli, F., Del Vecchio, L., Wetzels, J. F.M., Peters, H., Berg, U., Carvalho, F., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., Van Kooten, C., Rabelink, T., Reinders, M. E.J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Ferrario, F., Gutiérrez, E., Arce Terroba, J., Fortunato, M., Ozluk, Y., Kilicaslan, I., Steenberger, E., Soderberg, M., Da Costa Ferreira, A. C., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Bertoni, E., Cannata Ortiz, P., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Coppo, Rosanna, Troyanov, Stéphan, Bellur, Shubha, Cattran, Daniel, Cook, H. Terence, Feehally, John, Roberts, Ian S.D., Morando, Laura, Camilla, Roberta, Tesar, Vladimir, Lunberg, Sigrid, Gesualdo, Loreto, Emma, Francesco, Rollino, Cristiana, Amore, Alessandro, Praga, Manuel, Feriozzi, Sandro, Segoloni, Giuseppe, Pani, Antonello, Cancarini, Giovanni, Durlik, Magalena, Moggia, Elisabetta, Mazzucco, Gianna, Giannakakis, Costantinos, Honsova, Eva, Sundelin, B. Brigitta, Palma, Anna Maria Di, Ferrario, Franco, Gutierrez, Eduardo, Asunis, Anna Maria, Barratt, Jonathan, Tardanico, Regina, Perkowska-Ptasinska, Agnieszka, Maixnerova, D., Lundberg, S., Fuiano, L., Beltrame, G., Peruzzi, L., Polci, R., Colla, L., Angioi, A., Piras, D., Ravera, S., Ballarin, J., Di Giulio, S., Pugliese, F., Caliskan, Y., Locatelli, F., Del Vecchio, L., Wetzels, J. F.M., Peters, H., Berg, U., Carvalho, F., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Kalliakmani, P., Gerolymos, M., Galesic, K., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Kloster Smerud, H., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., Van Kooten, C., Rabelink, T., Reinders, M. E.J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Ferrario, F., Gutiérrez, E., Arce Terroba, J., Fortunato, M., Ozluk, Y., Kilicaslan, I., Steenberger, E., Soderberg, M., Da Costa Ferreira, A. C., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Galesic Ljubanovic, D., Bertoni, E., Cannata Ortiz, P., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., and Ioachim, E.

Abstract

The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin-angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m 2, the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.

Published
2014

7. Application of the International IgA Nephropathy Prediction Tool one or two years post-biopsy

Author

Sean J. Barbour, Rosanna Coppo, Hong Zhang, Zhi-Hong Liu, Yusuke Suzuki, Keiichi Matsuzaki, Lee Er, Heather N. Reich, Jonathan Barratt, Daniel C. Cattran, M.L. Russo, S. Troyanov, H.T. Cook, I. Roberts, V. Tesar, D. Maixnerova, S. Lundberg, L. Gesualdo, F. Emma, L. Fuiano, G. Beltrame, C. Rollino, A. Amore, R. Camilla, L. Peruzzi, M. Praga, S. Feriozzi, R. Polci, G. Segoloni, L. Colla, A. Pani, D. Piras, A. Angioi, G. Cancarini, S. Ravera, M. Durlik, E. Moggia, J. Ballarin, S. Di Giulio, F. Pugliese, I. Serriello, Y. Caliskan, M. Sever, I. Kilicaslan, F. Locatelli, L. Del Vecchio, J.F.M. Wetzels, H. Peters, U. Berg, F. Carvalho, A.C. da Costa Ferreira, M. Maggio, A. Wiecek, M. Ots-Rosenberg, R. Magistroni, R. Topaloglu, Y. Bilginer, M. D’Amico, M. Stangou, F. Giacchino, D. Goumenos, E. Papachristou, K. Galesic, C. Geddes, K. Siamopoulos, O. Balafa, M. Galliani, P. Stratta, M. Quaglia, R. Bergia, R. Cravero, M. Salvadori, L. Cirami, B. Fellstrom, H. Kloster Smerud, F. Ferrario, T. Stellato, J. Egido, C. Martin, J. Floege, F. Eitner, A. Lupo, P. Bernich, P. Menè, M. Morosetti, C. van Kooten, T. Rabelink, M.E.J. Reinders, J.M. Boria Grinyo, S. Cusinato, L. Benozzi, S. Savoldi, C. Licata, M. Mizerska-Wasiak, G. Martina, A. Messuerotti, A. Dal Canton, C. Esposito, C. Migotto, G. Triolo, F. Mariano, C. Pozzi, R. Boero, S. Bellur, G. Mazzucco, C. Giannakakis, E. Honsova, B. Sundelin, A.M. Di Palma, E. Gutiérrez, A.M. Asunis, J. Barratt, R. Tardanico, A. Perkowska-Ptasinska, J. Arce Terroba, M. Fortunato, A. Pantzaki, Y. Ozluk, E. Steenbergen, M. Soderberg, Z. Riispere, L. Furci, D. Orhan, D. Kipgen, D. Casartelli, D. Galesic Ljubanovic, H. Gakiopoulou, E. Bertoni, P. Cannata Ortiz, H. Karkoszka, H.J. Groene, A. Stoppacciaro, I. Bajema, J. Bruijn, X. Fulladosa Oliveras, J. Maldyk, E. Ioachim, N. Bavbek, T. Cook, C. Alpers, F. Berthoux, S. Bonsib, V. D’Agati, G. D’Amico, S. Emancipator, F. Emmal, F. Fervenza, S. Florquin, A. Fogo, H. Groene, M. Haas, P. Hill, R. Hogg, S. Hsu, T. Hunley, M. Hladunewich, C. Jennette, K. Joh, B. Julian, T. Kawamura, F. Lai, C. Leung, L. Li, P. Li, Z. Liu, A. Massat, B. Mackinnon, S. Mezzano, F. Schena, Y. Tomino, P. Walker, H. Wang, J. Weening, N. Yoshikawa, C.-H. Zeng, S. Shi, C. Nogi, H. Suzuki, K. Koike, K. Hirano, T. Yokoo, M. Hanai, K. Fukami, K. Takahashi, Y. Yuzawa, M. Niwa, Y. Yasuda, S. Maruyama, D. Ichikawa, T. Suzuki, S. Shirai, A. Fukuda, S. Fujimoto, H. Trimarchi, Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A. M., Russo, M. L., Ferrario, F., Gutiérrez, E., Asunis, A. M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Troyanov, S., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Ljubanovic, D. Galesic, Gakiopoulou, H., Bertoni, E., Cook, H. T., Cannata Ortiz, P., Karkoszka, H., Groene, H. J., Stoppacciaro, A., Bajema, I., Bruijn, J., Fulladosa Oliveras, X., Maldyk, J., Ioachim, E., Bavbek, N., Roberts, I., Cook, T., Alpers, C., Amore, A., Berthoux, F., Bonsib, S., D'Agati, V., D'Amico, G., Tesar, V., Emancipator, S., Emmal, F., Fervenza, F., Florquin, S., Fogo, A., Geddes, C., Groene, H., Haas, M., Hill, P., Maixnerova, D., Hogg, R., Hsu, S., Hunley, T., Hladunewich, M., Jennette, C., Joh, K., Julian, B., Kawamura, T., Lai, F., Leung, C., Lundberg, S., Li, L., Li, P., Liu, Z., Massat, A., Mackinnon, B., Mezzano, S., Schena, F., Tomino, Y., Walker, P., Wang, H., Gesualdo, L., Weening, J., Yoshikawa, N., Zeng, C.-H., Shi, S., Nogi, C., Suzuki, H., Koike, K., Hirano, K., Yokoo, T., Emma, F., Hanai, M., Fukami, K., Takahashi, K., Yuzawa, Y., Niwa, M., Yasuda, Y., Maruyama, S., Ichikawa, D., Suzuki, T., Shirai, S., Fuiano, L., Fukuda, A., Fujimoto, S., Trimarchi, H., Beltrame, G., Rollino, C., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Piras, D., Angioi, A., Cancarini, G., Ravera, S., Durlik, M., Moggia, E., Ballarin, J., Di Giulio, S., Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Del Vecchio, L., Wetzels, J. F. M., Peters, H., Berg, U., Carvalho, F., da Costa Ferreira, A. C., Maggio, M., Wiecek, A., Ots-Rosenberg, M., Magistroni, R., Topaloglu, R., Bilginer, Y., D'Amico, M., Stangou, M., Giacchino, F., Goumenos, D., Papachristou, E., Galesic, K., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Stellato, T., Egido, J., Martin, C., Flöge, Jürgen, Eitner, F., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M. E. J., Boria Grinyo, J. M., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Pathology, Center of Experimental and Molecular Medicine, Graduate School, and ACS - Heart failure & arrhythmias

Subjects
Adult, disease progression, end-stage kidney disease, IgA nephropathy, prediction tool, risk prediction, Biopsy, Glomerulonephritis, IGA, Prognosis, Cohort Studies, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Nephrology, Humans, Renal Insufficiency, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], Glomerular Filtration Rate
Abstract

Kidney international 102(1), 160-172 (2022). doi:10.1016/j.kint.2022.02.042, Published by Elsevier, New York, NY

Published
2022
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