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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

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, S.J., Coppo, R., Zhang, H., Liu, Z.H., Suzuki, Y., Matsuzaki, K., Katafuchi, R., Er, L., Espino-Hernandez, G., Kim, S.J., Reich, H.N., Feehally, J., Cattran, D.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., Giulio, S. di, Pugliese, F., Serriello, I., Caliskan, Y., Sever, M., Kilicaslan, I., Locatelli, F., Vecchio, L. del, Wetzels, J.F.M., Peters, H., Berg, U., Carvalho, F., Ferreira, A.C.D., 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., Fellstrorn, B., Smerud, H.K., Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Lupo, A., Bernich, P., Mene, R., Morosetti, M., Kooten, C. van, Rabelink, T., Reinders, M.E.J., Grinyo, J.M.B., Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Martina, G., Messuerotti, A., Canton, A. dal, Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Palma, A.M. di, Gutierrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J.A., Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., Ljubanovic, D.G., Gakiopoulou, H., Bertoni, E., Ortiz, P.C., Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., Oliveras, X.F., 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, 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.F., 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., Int IgA Nephropathy Network, and Pathology

Subjects
Adult, Male, medicine.medical_specialty, Risk Assessment, 01 natural sciences, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, 0101 mathematics, business.industry, Proportional hazards model, Clinical study design, 010102 general mathematics, Glomerulonephritis, IGA, Middle Aged, Models, Theoretical, medicine.disease, Clinical trial, Cohort, Female, business, Risk assessment, Kidney disease
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. Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy

Author

Feehally, J, Coppo, R, Troyanov, S, Bellur, Ss, Cattran, D, Cook, T, Roberts, Is, Verhave, Jc, Camilla, R, Vergano, L, Egido, J, Wiecek, A, Karkoszka, H, Tesar, V, Maixnerova, D, Ots-Rosenberg, M, Quaglia, M, Rollino, C, Magistroni, R, Cusinato, S, Cravero, R, Peruzzi, L, Lundberg, S, Gesualdo, L, Cancarini, G, Feriozzi, S, Ferrario, F, Emma, F, Fuiano, L, Beltrame, G, Amore, A, Praga, M, Polci, R, Biancone, L, Colla, L, Pani, A, Angioi, A, Piras, D, Ravera, S, Durlik, M, Moggia, E, Ballarin, J, Di Giulio, S, Pierucci, A, Caliskan, Y, Sever, M, Kilicaslan, I, Locatelli, F, Del Vecchio, L, Wetzels, Jf, Peters, H, Berg, U, Carvalho, F, da Costa Ferreira AC, Maggio, M, 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, Bergia, R, Salvadori, M, Cirami, L, Fellstrom, B, Kloster Smerud, H, Stellato, T, Cleary, C, Floege, J, Rauen, T, Lupo, A, Bernich, P, Menè, P, Morosetti, M, van Kooten, C, Rabelink, T, Reinders, Me, Boria Grinyo JM, 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, Di Palma AM, Boero, R, Mazzucco, G, Giannakakis, C, Honsova, E, Sundelin, B, Gutiérrez, E, Asunis, Am, 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, Groene, Hj, Stoppacciaro, A, Bajema, I, Bruijn, J, Fulladosa Oliveras, X, Maldyk, J, and Ioachim, E.

Subjects
Male, Physiology, medicine.medical_treatment, IgA nephropathy, Tonsillectomy, Risk factors, Progression of chronic renal failure, 030232 urology & nephrology, 030204 cardiovascular system & hematology, urologic and male genital diseases, Gastroenterology, Progression of chronic renal failure, Cohort Studies, Kidney Failure, Glomerulonephritis, 0302 clinical medicine, Ethnicity, Chronic, Proteinuria, medicine.diagnostic_test, Age Factors, IgA nephropathy, Middle Aged, Europe, Treatment Outcome, Nephrology, Cohort, Disease Progression, Female, Renal biopsy, medicine.symptom, Glomerular Filtration Rate, Cohort study, Adult, medicine.medical_specialty, Urology, Renal function, Ethnic Groups, Nephropathy, iga nephropathy, tonsillectomy, risk factors, progression of chronic renal failure, 03 medical and health sciences, Sex Factors, Physiology (medical), Internal medicine, Risk factors, Tonsillectomy, medicine, Humans, Follow-Up Studies, Glomerulonephritis, IGA, Kidney Failure, Chronic, Propensity Score, Retrospective Studies, IGA, business.industry, Retrospective cohort study, medicine.disease, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract

Background: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. Methods: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. Results: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. Conclusion: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

Published
2016

6. Inter-observer agreement in laryngeal pre-neoplastic lesions

Author

Sulen, Sarioglu, Fulya, Cakalagaoglu, Sahande, Elagoz, Unsal, Han, Unsal, Ersoy, Demet, Etit, Sema, Hucumenoglu, Ilgin, Karaman, Fulya, Koybasioglu, Sezer, Kulacoglu, Irem Onur, Paker, Gulay, Ozbilim, Yasemin, Ozluk, Ugur, Pabuccuoglu, Arzu, Ruacan, Selda, Seckin, Aysun, Uguz, Ozlem, Saraydaroglu, Ali, Veral, Dilek, Yilmazbayhan, Hulya, Ellidokuz, Sarioglu, S., Department of Pathology, Dokuz Eylul University Faculty of Medicine, 35340 Inciralti, Izmir, Turkey -- Cakalagaoglu, F., Department of Pathology, Yesilyurt Ataturk Research and Education Hospital, Izmir, Turkey -- Elagoz, S., Department of Pathology, Cumhuriyet University Faculty of Medicine, Sivas, Turkey -- Ersoy, U., Department of Pathology, Ankara Diskapi Research and Education Hospital, Ankara, Turkey -- Etit, D., Department of Pathology, Yesilyurt Ataturk Research and Education Hospital, Izmir, Turkey -- Hucumenoglu, S., Department of Pathology, Ankara Diskapi Research and Education Hospital, Ankara, Turkey -- Karaman, I., Department of Pathology, Dokuz Eylul University Faculty of Medicine, 35340 Inciralti, Izmir, Turkey -- Koybasioglu, F., Department of Pathology, Ankara Diskapi Research and Education Hospital, Ankara, Turkey -- Kulacoglu, S., Department of Pathology, Ankara Numune Research and Education Hospital, Ankara, Turkey -- Paker, I.O., Department of Pathology, Ankara Diskapi Research and Education Hospital, Ankara, Turkey -- Ozbilim, G., Department of Pathology, Akdeniz University Faculty of Medicine, Ankara, Turkey -- Ozluk, Y., Department of Pathology, Istanbul University Faculty of Medicine, Istanbul, Turkey -- Pabuccuoglu, U., Department of Pathology, Dokuz Eylul University Faculty of Medicine, 35340 Inciralti, Izmir, Turkey -- Ruacan, A., Department of Pathology, Hacettepe University Faculty of Medicine, Ankara, Turkey -- Seckin, S., Department of Pathology, Ankara Numune Research and Education Hospital, Ankara, Turkey -- Uguz, A., Department of Pathology, Cukurova University Faculty of Medicine, Adana, Turkey -- Saraydaroglu, O., Department of Pathology, Uludag University Faculty of Medicine, Bursa, Turkey -- Veral, A., Department of Pathology, Ege University Faculty of Medicine, Izmir, Turkey -- Yilmazbayhan, D., Department of Pathology, Istanbul University Faculty of Medicine, Istanbul, Turkey -- Ellidokuz, H., Preventive Oncology, Dokuz Eylul University Institute of Oncology, Izmir, Turkey, and Çukurova Üniversitesi

Subjects
Larynx, Mild Dysplasia, Pathology, medicine.medical_specialty, Biopsy, World Health Organization, Pathology and Forensic Medicine, medicine, Humans, Pre-neoplastic lesions, Laryngeal Neoplasms, Moderate Dysplasia, Squamous intraepithelial neoplasia classification, Observer Variation, Intraepithelial neoplasia, Original Paper, Pathology, Clinical, medicine.diagnostic_test, business.industry, Carcinoma in situ, Ljubljana classification, Laryngeal Neoplasm, medicine.disease, medicine.anatomical_structure, Oncology, Otorhinolaryngology, Inter-observer agreement, Carcinoma, Squamous Cell, business, Precancerous Conditions, Kappa, World Health Organization classification, Carcinoma in Situ
Abstract

Humana Press Inc., In this series, laryngeal preneoplastic lesions were evaluated by the classifications of the World Health Organization (WHOC), Ljubljana (LC) and squamous intraepithelial neoplasia (SINC) by multiple observers. The inter-observer agreement (IA) by WHOC for laryngeal lesions had been previously evaluated, but to the best of our knowledge, there are no data for LC and SINC. H&E stained slides from 42 laryngeal biopsies were evaluated by fourteen participants according to WHOC and LC, and SINC was additionally applied by 6. The results were analyzed statistically. The diagnoses which were favored by most participants for each case, according to WHOC, were as follows: squamous cell hyperplasia (n = 5; 12%), mild dysplasia (n = 11; 26.2%), moderate dysplasia (n = 12; 28.6%), severe dysplasia (n = 7; 16.7%), carcinoma in situ (n = 5; 12%), and invasive squamous cell carcinoma (n = 2; 4.8%). There was a significant difference between the participants for all three classifications; some participants gave lower or higher scores than the others. The mean correlation coefficients (MCC) of the participants were higher for WHOC compared to LC (0.55 ± 0.15 and 0.48 ± 0.14, respectively). The mean linear-weighted kappa (wKappa) values of participants were not significantly different (0.42 ± 0.10, 0.41 ± 0.12 and 0.37 ± 0.07 for WHOC, LC and SINC, respectively). The kappa values in this series are in agreement with those in previous literature for WHOC, and the similar results obtained for LC and SINC are novel findings. Although the MCC of WHOC was higher, as the wkappa was not significantly different, the findings in this series are not in favor of any of the classifications for better IA for pre-neoplastic laryngeal lesions. © 2010 Humana., Sarioglu, S.; Department of Pathology, Dokuz Eylul University Faculty of Medicine, 35340 Inciralti, Izmir, Turkey; email: sulen.sarioglu@deu.edu.tr

Published
2010

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