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5. Development and testing of an artificial intelligence tool for predicting end-stage kidney disease in patients with immunoglobulin A nephropathy

Author

Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Coppo, R., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., Feehally, J., 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., Papasotiriou, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Rauen, T., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Grinyo, J.M. Boria, Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Canton, A. Dal, Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Mazzucco, Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., GalesicLjubanovic, D., Gakiopoulou, H., Bertoni, E., Ortiz, P. Cannata, Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., FulladosaOliveras, X., Maldyk, J., Ioachim, E., Abbrescia, Daniela, Kouri, Nikoleta, Stangou, Maria, Papagianni, Aikaterini, Scolari, Francesco, Delbarba, Elisa, Bonomini, Mario, Piscitani, Luca, Stallone, Giovanni, Infante, Barbara, Godeas, Giulia, Madio, Desiree, Biancone, Luigi, Campagna, Marco, Zaza, Gianluigi, Squarzoni, Isabella, Cangemi, Concetta, Schena, Francesco Paolo, Anelli, Vito Walter, Trotta, Joseph, Di Noia, Tommaso, Manno, Carlo, Tripepi, Giovanni, D’Arrigo, Graziella, Chesnaye, Nicholas C., Russo, Maria Luisa, Zoccali, Carmine, Tesar, Vladimir, and Coppo, Rosanna

Published
2021
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8. A meta-analysis of GFR slope as a surrogate endpoint for kidney failure

Author

Inker, LA, Collier, W, Greene, T, Miao, S, Chaudhari, J, Appel, GB, Badve, SV ; https://orcid.org/0000-0003-2269-312X, Caravaca-Fontán, F, Del Vecchio, L, Floege, J, Goicoechea, M, Haaland, B, Herrington, WG, Imai, E, Jafar, TH, Lewis, JB, Li, PKT, Maes, BD, Neuen, BL ; https://orcid.org/0000-0001-9276-8380, Perrone, RD, Remuzzi, G, Schena, FP, Wanner, C, Wetzels, JFM, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Heerspink, HJL, Estacio, RO, Hanratty, R, Chalmers, J ; https://orcid.org/0000-0002-9931-0580, Canetta, P, Barrett, B, Neal, B ; https://orcid.org/0000-0002-0490-7465, Perkovic, V ; https://orcid.org/0000-0002-4257-7620, Mahaffey, KW, Johnson, D, Jardine, M ; https://orcid.org/0000-0002-0160-2375, von Eynatten, M, Verde, E, Verdalles, U, Arroyo, D, Chapman, A, Torres, V, Yu, A, Brosnahan, G, Hannedouche, T, Chow, KM, Szeto, CC, Leung, CB, Xie, D, Hou, FF, Dwyer, J, Pohl, MA, Raz, I, Hunsicker, LG, Vanacker, A, Malfait, T, Maschio, G, Locatelli, F, Blankestijn, PJ, van Zuilen, A, Kobayashi, F, Makino, H, Chan, JCN, Andrulli, S, Pozzi, C, Casartelli, D, Praga, M, Trujillo, H, Cavero, T, Sevillano, A, Ruggenenti, P, Perna, A, Carrara, F, Keane, WF, Manno, C, Haynes, R, Baigent, C, Landray, M, Rauen, T, Seikrit, C, Wied, S, Toto, RD, de Jong, PE, Saddelli, M, Inker, LA, Collier, W, Greene, T, Miao, S, Chaudhari, J, Appel, GB, Badve, SV ; https://orcid.org/0000-0003-2269-312X, Caravaca-Fontán, F, Del Vecchio, L, Floege, J, Goicoechea, M, Haaland, B, Herrington, WG, Imai, E, Jafar, TH, Lewis, JB, Li, PKT, Maes, BD, Neuen, BL ; https://orcid.org/0000-0001-9276-8380, Perrone, RD, Remuzzi, G, Schena, FP, Wanner, C, Wetzels, JFM, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Heerspink, HJL, Estacio, RO, Hanratty, R, Chalmers, J ; https://orcid.org/0000-0002-9931-0580, Canetta, P, Barrett, B, Neal, B ; https://orcid.org/0000-0002-0490-7465, Perkovic, V ; https://orcid.org/0000-0002-4257-7620, Mahaffey, KW, Johnson, D, Jardine, M ; https://orcid.org/0000-0002-0160-2375, von Eynatten, M, Verde, E, Verdalles, U, Arroyo, D, Chapman, A, Torres, V, Yu, A, Brosnahan, G, Hannedouche, T, Chow, KM, Szeto, CC, Leung, CB, Xie, D, Hou, FF, Dwyer, J, Pohl, MA, Raz, I, Hunsicker, LG, Vanacker, A, Malfait, T, Maschio, G, Locatelli, F, Blankestijn, PJ, van Zuilen, A, Kobayashi, F, Makino, H, Chan, JCN, Andrulli, S, Pozzi, C, Casartelli, D, Praga, M, Trujillo, H, Cavero, T, Sevillano, A, Ruggenenti, P, Perna, A, Carrara, F, Keane, WF, Manno, C, Haynes, R, Baigent, C, Landray, M, Rauen, T, Seikrit, C, Wied, S, Toto, RD, de Jong, PE, and Saddelli, M

Abstract

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min−1 per 1.73 m2 or kidney failure with replacement therapy). We used a Bayesian mixed-effects meta-regression model to relate treatment effects on GFR slope with those on the clinical endpoint across all studies and by disease groups (diabetes, glomerular diseases, CKD or cardiovascular diseases). Treatment effects on the clinical endpoint were strongly associated with treatment effects on total slope (median coefficient of determination (R2) = 0.97 (95% Bayesian credible interval (BCI) 0.82–1.00)) and moderately associated with those on chronic slope (R2 = 0.55 (95% BCI 0.25–0.77)). There was no evidence of heterogeneity across disease. Our results support the use of total slope as a primary endpoint for clinical trials of CKD progression.

Published
2023

12. IgA-Nephropathie und Schönlein-Henoch-Purpura

Author

Rauen, T. and Floege, J.

Abstract

Die IgA-Nephropathie (IgAN) ist die häufigste primäre Glomerulonephritis in der westlichen Welt. Ganz überwiegend manifestiert sie sich oligosymptomatisch mit minimalen Urinbefunden im jüngeren Erwachsenenalter. Die meisten Patienten nehmen einen unkomplizierten Verlauf, jedoch entwickeln etwa 20–30 % ein terminales Nierenversagen. Zu den Risikofaktoren für einen progredienten Verlauf zählen eine ausgeprägte Proteinurie, eine eingeschränkte Nierenfunktion, das Vorliegen einer arteriellen Hypertonie sowie der Nachweis einer ausgeprägten tubulointerstitiellen Fibrose zum Zeitpunkt der Diagnose. In den letzten Jahren konnten genetische und immunologische Mechanismen aufgedeckt werden, denen zufolge die IgAN zunehmend als autoimmun (mit)bedingte Erkrankung verstanden wird. Dennoch bleibt – gerade auch nach den neuesten Therapiestudien – der Stellenwert einer immunsuppressiven Therapie höchst fragwürdig. Vielmehr zeigt sich, dass forcierte Supportivmaßnahmen im therapeutischen Mittelpunkt stehen sollten. IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis in Western countries. In the vast majority of cases IgAN is manifested in young adulthood with only minimal findings in urine. In long-term observations most IgAN patients experience a benign disease course; however, 20–30 % develop end-stage renal failure. Extensive proteinuria, reduced renal function, arterial hypertension and the presence of tubulointerstitial fibrosis at the time of diagnosis constitute well-established risk factors for a progressive course of the disease. Novel genetic and immunological findings underscore the pathogenetic concept of IgAN as an autoimmune-mediated disease; nevertheless, according to the results of recent therapeutic clinical trials, optimized supportive strategies should be the mainstay of treatment for IgAN patients and the value of immunosuppressive therapy remains highly questionable.

Published
2024
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18. 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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30. Development and testing of an artificial intelligence tool for predicting end-stage kidney disease in patients with immunoglobulin A nephropathy

Author

Schena, Francesco Paolo, Anelli, Vito Walter, Trotta, Joseph, Di Noia, Tommaso, Manno, Carlo, Tripepi, Giovanni, D’Arrigo, Graziella, Chesnaye, Nicholas C., Russo, Maria Luisa, Stangou, Maria, Papagianni, Aikaterini, Zoccali, Carmine, Tesar, Vladimir, Coppo, Rosanna, Tesar, V., Maixnerova, D., Lundberg, S., Gesualdo, L., Emma, F., Fuiano, L., Beltrame, G., Rollino, C., Coppo, R., Amore, A., Camilla, R., Peruzzi, L., Praga, M., Feriozzi, S., Polci, R., Segoloni, G., Colla, L., Pani, A., Angioi, A., Piras, L., Feehally, J., 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., Papasotiriou, M., Galesic, K., Toric, L., Geddes, C., Siamopoulos, K., Balafa, O., Galliani, M., Stratta, P., Quaglia, M., Bergia, R., Cravero, R., Salvadori, M., Cirami, L., Fellstrom, B., Smerud, H. Kloster, Ferrario, F., Stellato, T., Egido, J., Martin, C., Floege, J., Eitner, F., Rauen, T., Lupo, A., Bernich, P., Menè, P., Morosetti, M., van Kooten, C., Rabelink, T., Reinders, M.E.J., Grinyo, J.M. Boria, Cusinato, S., Benozzi, L., Savoldi, S., Licata, C., Mizerska-Wasiak, M., Roszkowska-Blaim, M., Martina, G., Messuerotti, A., Canton, A. Dal, Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Mazzucco, Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Ferrario, F., Gutiérrez, E., Asunis, A.M., Barratt, J., Tardanico, R., Perkowska-Ptasinska, A., Terroba, J. Arce, Fortunato, M., Pantzaki, A., Ozluk, Y., Steenbergen, E., Soderberg, M., Riispere, Z., Furci, L., Orhan, D., Kipgen, D., Casartelli, D., GalesicLjubanovic, D., Gakiopoulou, H., Bertoni, E., Ortiz, P. Cannata, Karkoszka, H., Groene, H.J., Stoppacciaro, A., Bajema, I., Bruijn, J., FulladosaOliveras, X., Maldyk, J., Ioachim, E., Abbrescia, Daniela, Kouri, Nikoleta, Stangou, Maria, Papagianni, Aikaterini, Scolari, Francesco, Delbarba, Elisa, Bonomini, Mario, Piscitani, Luca, Stallone, Giovanni, Infante, Barbara, Godeas, Giulia, Madio, Desiree, Biancone, Luigi, Campagna, Marco, Zaza, Gianluigi, Squarzoni, Isabella, and Cangemi, Concetta

Abstract

We have developed an artificial neural network prediction model for end-stage kidney disease (ESKD) in patients with primary immunoglobulin A nephropathy (IgAN) using a retrospective cohort of 948 patients with IgAN. Our tool is based on a two-step procedure of a classifier model that predicts ESKD, and a regression model that predicts development of ESKD over time. The classifier model showed a performance value of 0.82 (area under the receiver operating characteristic curve) in patients with a follow-up of five years, which improved to 0.89 at the ten-year follow-up. Both models had a higher recall rate, which indicated the practicality of the tool. The regression model showed a mean absolute error of 1.78 years and a root mean square error of 2.15 years. Testing in an independent cohort of 167patients with IgAN found successful results for 91% of the patients. Comparison of our system with other mathematical models showed the highest discriminant Harrell C index at five- and ten-years follow-up (81% and 86%, respectively), paralleling the lowest Akaike information criterion values (355.01 and 269.56, respectively). Moreover, our system was the best calibrated model indicating that the predicted and observed outcome probabilities did not significantly differ. Finally, the dynamic discrimination indexes of our artificial neural network, expressed as the weighted average of time-dependent areas under the curve calculated at one and two years, were 0.80 and 0.79, respectively. Similar results were observed over a 25-year follow-up period. Thus, our tool identified individuals who were at a high risk of developing ESKD due to IgAN and predicted the time-to-event endpoint. Accurate prediction is an important step toward introduction of a therapeutic strategy for improving clinical outcomes.

Published
2021
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31. 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

38. Transplantation: basic science and immune-tolerance

Author

Sugawara, M., primary, Ichimura, S., additional, Kokubo, K., additional, Shimbo, T., additional, Hirose, M., additional, Kobayashi, H., additional, Hribova, P., additional, Brabcova, I., additional, Honsova, E., additional, Viklicky, O., additional, Kute, V. B., additional, Shah, P. R., additional, Vanikar, A. V., additional, Gumber, M. R., additional, Patel, H. V., additional, Modi, P. R., additional, Trivedi, H. L., additional, Trivedi, V. B., additional, Nusrath, S., additional, Minz, M., additional, Walker Minz, R., additional, Sharma, A., additional, Singh, S., additional, Jha, V., additional, Joshi, K., additional, Richter, R., additional, Kohler, S., additional, Qidan, S., additional, Scheuermann, E., additional, Kachel, H.-G., additional, Gossmann, J., additional, Gauer, S., additional, Seifried, E., additional, Geiger, H., additional, Seidl, C., additional, Hauser, I. A., additional, Hanssen, L., additional, Frye, B., additional, Ostendorf, T., additional, Alidousty, C., additional, Djudjaj, S., additional, Boor, P., additional, Rauen, T., additional, Floege, J., additional, Mertens, P., additional, Raffetseder, U., additional, Garcia-Cenador, B., additional, Lopez-Novoa, J. M., additional, Iniguez, M., additional, Fernandez, V., additional, Perez de Obanos, P., additional, Ruiz, J., additional, Sanz-Gimenez, J. R., additional, Lopez-Marcos, J. F., additional, Garcia-Criado, J., additional, Van Craenenbroeck, A. H., additional, Anguille, S. H., additional, Jurgens, A., additional, Cools, N., additional, Van Camp, K., additional, Stein, B., additional, Nijs, G., additional, Berneman, Z., additional, Ieven, M., additional, Van Damme, P., additional, Van Tendeloo, V., additional, Verpooten, G. A., additional, Gohel, K., additional, Hegde, U., additional, Gang, S., additional, Rajapurkar, M., additional, Erdogmus, S., additional, Sengul, S., additional, Kocak, S., additional, Kurultak, I., additional, Kutlay, S., additional, Keven, K., additional, Erbay, B., additional, Erturk, S., additional, Kimura, S., additional, Imura, J., additional, Atsumi, H., additional, Fujimoto, K., additional, Chikazawa, Y., additional, Nakagawa, M., additional, Hayama, T., additional, Okuyama, H., additional, Yamaya, H., additional, Yokoyama, H., additional, Libetta, C., additional, Canevari, M., additional, Sepe, V., additional, Margiotta, E., additional, Meloni, F., additional, Martinelli, C., additional, Borettaz, I., additional, Esposito, P., additional, Portalupi, V., additional, Morosini, M., additional, Solari, N., additional, Dal Canton, A., additional, Rusai, K., additional, Schmaderer, C., additional, Hermans, R., additional, Lutz, J., additional, Heemann, U., additional, Baumann, M., additional, Cantaluppi, V., additional, Tamagnone, M., additional, Dellepiane, S., additional, Medica, D., additional, Dolla, C., additional, Messina, M., additional, Manzione, A. M., additional, Tognarelli, G., additional, Ranghino, A., additional, Biancone, L., additional, Camussi, G., additional, Segoloni, G. P., additional, Ozkurt, S., additional, Sahin, G., additional, Degirmenci, N., additional, Temiz, G., additional, Musmul, A., additional, Birdane, A., additional, Tek, M., additional, Tekin, N., additional, Akyuz, F., additional, Yalcin, A. U., additional, and Lopez-Valverde, A., additional

Published
2011
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46. Immunsuppressive Behandlung von Glomerulonephritiden.

Author

Rauen, T., Floege, J., and Moeller, M.J.

Abstract

Copyright of Der Nephrologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2015
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49. Neuronal-induced and glutamate-dependent activation of glial glutamate transporter function.

Author

Poitry-Yamate, C.L., Vutskits, L., and Rauen, T.

Subjects
NEURONS, ASTROCYTES, CENTRAL nervous system
Abstract

The activity of high-affinity glutamate transporters is essential for the normal function of the mammalian central nervous system. Using a combined pharmacological, confocal immunocytochemical, enzyme-based microsensor and fluorescence imaging approach, we examined glutamate uptake and transporter protein localization in single astrocytes of neuron-containing and neuron-free microislands prior to presynaptic transmitter secretion and during functional neuronal activity. Here, we report that the presence or absence of neurons strikingly affects the uptake capacity of the astroglial glutamate transporters GLT1 and GLAST1. Induction of transporter function is activated by neurons and this effect is mimicked by pre-incubation of astrocytes with micromolar concentrations of glutamate. Moreover, increased glutamate transporter activation is reproduced by endogenous release of glutamate via activation of neuronal nicotinic receptors. The increase in transport activity is dependent on neuronal release of glutamate, is associated with the local redistribution (clustering) of GLT1 and GLAST1 but is independent of transporter synthesis and of glutamate receptor activation. Together, these results suggest an activity-dependent neuronal feedback system for rapid astroglial glutamate transporter regulation where neuron-derived glutamate is the physiological signal that triggers transporter function. [ABSTRACT FROM AUTHOR]

Published
2002
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50. A Rational Approach to the Design of Selective Substrates and Potent Nontransportable Inhibitors of the Excitatory Amino Acid Transporter EAAC1 (EAAT3). New Glutamate and Aspartate Analogues as Potential Neuroprotective Agents

Author

Campiani, G., Angelis, M. De, Armaroli, S., Fattorusso, C., Catalanotti, B., Ramunno, A., Nacci, V., Novellino, E., Grewer, C., Ionescu, D., Rauen, T., Griffiths, R., Sinclair, C., Fumagalli, E., and Mennini, T.

Abstract

Two three-dimensional receptor interaction models for EAAT substrates and nontransportable inhibitors have been developed, and new glutamate (Glu) and aspartate (Asp) analogues have been synthesized. The analogues 1a and 3 represent novel lead compounds for the development of EAAT substrates and nontransportable inhibitors, selective for EAATs over iGluRs, as possible neuroprotective agents useful to minimize the progression of chronic or acute neurodegenerative diseases. The role played by the protonatable amine function in the interaction with EAATs has been discussed.

Published
2001

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