Search

Your search keyword '"Barratt J"' showing total 627 results
Start Over Author "Barratt J" Language english
627 results on '"Barratt J"'

1. Insights on Nefecon®, a Targeted-Release Formulation of Budesonide and Its Selective Immunomodulatory Effects in Patients with IgA Nephropathy

Author

Barratt J, Kristensen J, Pedersen C, and Jerling M

Subjects
drug delivery, biomarkers, pharmacokinetics, galt, Therapeutics. Pharmacology, RM1-950
Abstract

Jonathan Barratt,1 Jens Kristensen,2 Christian Pedersen,2 Markus Jerling3 1College of Life Sciences, University of Leicester, Leicester, UK; 2Calliditas Therapeutics AB, Stockholm, Sweden; 3Markus Jerling Consulting AB, Stockholm, SwedenCorrespondence: Jonathan Barratt, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK, Tel +44 0116 258 8043, Email jb81@leicester.ac.ukAbstract: Immunoglobulin A nephropathy (IgAN) is a chronic, immune-mediated kidney disease characterized by the deposition of galactose-deficient immunoglobulin A1 (Gd-IgA1) in the kidneys. Excess Gd-IgA1 production in patients with IgAN is located within the mucosa-associated lymphoid tissue, particularly within the lamina propria in the distal ileum. Nefecon® is a targeted-release formulation of the corticosteroid budesonide, which became the first treatment approved by the US Food and Drug Administration (FDA; brand name, TARPEYO®) and European Medicines Agency (EMA; KINPEYGO®) for patients with primary IgAN at risk of rapid disease progression, after demonstrating clinically significant reduction of proteinuria in an interim analysis of the Phase III NefIgArd trial. After showing a significant reduction in estimated glomerular filtration rate decline in the full 2-year analysis of the trial, Nefecon was granted full approval by the FDA to reduce the loss of kidney function. Nefecon was specifically designed to deliver budesonide to the distal ileum, selectively targeting excess Gd-IgA1 production in the gut-associated lymphoid tissue. In this review, we describe the properties of Nefecon and the evidence to date that confirms its localized treatment effect. We also present unpublished evidence from Phase I trials investigating the pharmacokinetics and cortisol suppression effects of Nefecon in healthy participants. These studies demonstrated that Nefecon has a distinct pharmacokinetic profile from other budesonide products, allowing for targeted, localized action in the distal ileum. When considered alongside existing clinical trial data showing the effect of Nefecon on gut-associated biomarkers, available evidence indicates that Nefecon has a selective immunomodulatory mechanism of action and a direct disease-modifying effect in patients with IgAN, while having low systemic exposure and adverse effects.Keywords: drug delivery, biomarkers, pharmacokinetics, GALT

Published
2024

2. Evidence from the large VALIGA cohort validates the subclassification of focal segmental glomerulosclerosis in IgA nephropathy

Author

Coppo, R., Feehaly, J., Troyanov, S., Cattran, D.C., Cook, H.T., Roberts, I., Radcliffe, John, Russo, M.L., 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., Papagianni, K., Stangou, M., Giacchino, F., Goumenos, D., Papasotirious, M., Kalliakmani, P., Gerolymos, 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., Kloster Smerud, H., Ferrario, F., 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., Roszkowska-Blaim, M., Hryszko, T., Klinger, M., Kamińska, D., Krajewska, M., Martina, G., Messuerotti, A., Dal Canton, A., Esposito, C., Migotto, C., Triolo, G., Mariano, F., Pozzi, C., Boero, R., Cambier, A., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Diomedi-Casadei, F., Gutiérrez, 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., Royal, V., Bellur, Shubha S., Troyanov, Stéphan, Vorobyeva, Olga, Coppo, Rosanna, and Roberts, Ian S.D.

Published
2024
Full Text
View/download PDF

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

Author

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., Papachristou, E., Galesic, K., 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., 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., Bellur, S., Mazzucco, G., 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., 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., Ioachim, 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, 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., Barbour, Sean J., Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Er, Lee, Reich, Heather N., Barratt, Jonathan, and Cattran, Daniel C.

Published
2022
Full Text
View/download PDF

5. A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function

Author

Heerspink, Hiddo J.L., Wheeler, David C., Chertow, Glenn, Correa-Rotter, Ricardo, Greene, Tom, Hou, Fan Fan, McMurray, John, Rossing, Peter, Toto, Robert, Stefansson, Bergur, Langkilde, Anna Maria, Maffei, L.E., Raffaele, P., Solis, S.E., Arias, C.A., Aizenberg, D., Luquez, C., Zaidman, C., Cluigt, N., Mayer, M., Alvarisqueta, A., Wassermann, A., Maldonado, R., Bittar, J., Maurich, M., Gaite, L.E., Garcia, N., Sivak, L., Ramallo, P.O., Santos, J.C., Garcia Duran, R., Oddino, J.A., Maranon, A., Maia, L.N., Avila, D.D., Barros, E.J.G., Vidotti, M.H., Panarotto, D., Noronha, I.D.L., Turatti, L.A.A., Deboni, L., Canziani, M.E., Riella, M.C., Bacci, M.R., Paschoalin, R.P., Franco, R.J., Goldani, J.C., St-Amour, E., Steele, A.W., Goldenberg, R., Pandeya, S., Bajaj, H., Cherney, D., Kaiser, S.M., Conway, J.R., Chow, S.S., Bailey, G., Lafrance, J., Winterstein, J., Cournoyer, S., Gaudet, D., Madore, F., Houlden, R.L., Dowell, A., Langlois, M., Muirhead, N., Khandwala, H., Levin, A., Hou, F., Xue, Y., Zuo, L., Hao, C., Ni, Z., Xing, C., Chen, N., Dong, Y., Zhou, R., Xiao, X., Zou, Y., Wang, C., Liu, B., Chen, Q., Lin, M., Luo, Q., Zhang, D., Wang, J., Chen, M., Wang, X., Zhong, A., Dong, J., Zhu, C., Yan, T., Luo, P., Ren, Y., Pai, P., Li, D., Zhang, R., Zhang, J., Xu, M., Zhuang, Y., Kong, Y., Yao, X., Peng, X., Persson, F.I., Hansen, T.K., Borg, R., Pedersen Bjergaard, U., Hansen, D., Hornum, M., Haller, H., Klausmann, G., Tschope, D., Kruger, T., Gross, P., Hugo, C., Obermuller, N., Rose, L., Mertens, P., Zeller-Stefan, H., Fritsche, A., Renders, L., Muller, J., Budde, K., Schroppel, B., Wittmann, I., Voros, P., Dudas, M., Tabak, G.A., Kirschner, R., Letoha, A., Balku, I., Hermanyi, Z., Zakar, G., Mezei, I., Nagy, G.G., Lippai, J., Nemeth, A., Khullar, D., Gowdaiah, P.K., Fernando Mervin, E., Rao, V.A., Dewan, D., Goplani, K., Maddi, V.S.K., Vyawahare, M.S., Pulichikkat, R.K., Pandey, R., Sonkar, S.K., Gupta, V.K., Agarwal, S., Asirvatham, A.J., Ignatius, A., Chaubey, S., Melemadathil, S., Alva, H., Kadam, Y., Shimizu, H., Sueyoshi, A., Takeoka, H., Abe, Y., Imai, T., Onishi, Y., Fujita, Y., Tokita, Y., Oura, M., Makita, Y., Idogaki, A., Koyama, R., Kikuchi, H., Kashihara, N., Hayashi, T., Ando, Y., Tanaka, T., Shimizu, M., Hidaka, S., Gohda, T., Tamura, K., Abe, M., Kamijo, Y., Imasawa, T., Takahashi, Y., Nakayama, M., Tomita, M., Hirano, F., Fukushima, Y., Kiyosue, A., Kurioka, S., Imai, E., Kitagawa, K., Waki, M., Wada, J., Uehara, K., Iwatani, H., Ota, K., Shibazaki, S., Katayama, K., Narita, I., Iinuma, M., Matsueda, S., Sasaki, S., Yokochi, A., Tsukamoto, T., Yoshimura, T., Kang, S., Lee, S., Lim, C.S., Chin, H., Joo, K.W., Han, S.Y., Chang, T.I., Park, S., Park, H., Park, C.W., Han, B.G., Cha, D.R., Yoon, S.A., Kim, W., Kim, S.W., Ryu, D., Correa Rotter, R., Irizar Santana, S.S., Hernandez Llamas, G., Valdez Ortiz, R., Secchi Nicolas, N.C., Gonzalez Galvez, G., Lazcano Soto, J.R., Bochicchio Riccardelli, T., Bayram Llamas, E.A., Ramos Ibarra, D.R., Melo, M.G.S., Gonzalez Gonzalez, J.G., Sanchez Mijangos, J.H., Madero Robalo, M., Garcia Castillo, A., Manrique, H.A., Farfan, J.C., Vargas, R., Valdivia, A., Dextre, A., Escudero, E., Calderon Ticona, J.R., Gonzales, L., Villena, J., Leon, L., Molina, G., Saavedra, A., Garrido, E., Arbanil, H., Vargas Marquez, S., Rodriguez, J., Isidto, R., Villaflor, A.J., Gumba, M.A., Tirador, L., Comia, R.S., Sy, R.A., Guanzon, M.L.V.V., Aquitania, G., De Asis, N.C., Silva, A.A., Romero, C.M., Lim, M.E., Danguilan, R.A., Nowicki, M., Rudzki, H., Landa, K., Kucharczyk-Bauman, I., Gogola-Migdal, B., Golski, M., Olech-Cudzik, A., Stompor, T., Szczepanik, T., Miklaszewicz, B., Sciborski, R., Kuzniewski, M., Ciechanowski, K., Wronska, D., Klatko, W., Mazur, S., Popenda, G., Myslicki, M., Bolieva, L.Z., Berns, S., Galyavich, A., Abissova, T., Karpova, I., Platonov, D., Koziolova, N., Kvitkova, L., Nilk, R., Medina, T., Rebrov, A., Rossovskaya, M., Sinitsina, I., Vishneva, E., Zagidullin, N., Novikova, T., Krasnopeeva, N., Magnitskaya, O., Antropenko, N., Batiushin, M., Escudero Quesada, V., Barrios Barrea, C., Espinel Garauz, E., Cruzado Garrit, J.M., Morales Portillo, C., Gorriz Teruel, J.L., Cigarran Guldris, S., Praga Terente, M., Robles Perez-Monteoliva, N.R., Tinahones Madueno, F.J., Soto Gonzalez, A., Diaz Rodriguez, C., Furuland, H., Saeed, A., Dreja, K., Spaak, J., Bruchfeld, A., Kolesnyk, M., Levchenko, O., Pyvovarova, N., Stus, V., Doretskyy, V., Korobova, N., Horoshko, O., Katerenchuk, I., Mostovoy, Y.M., Orynchak, M., Legun, O., Dudar, I., Bilchenko, O., Andreychyn, S., Levchenko, A., Zub, L., Tereshchenko, N., Topchii, I., Ostapenko, T., Bezuglova, S., Kopytsya, M., Turenko, O., Mark, P., Barratt, J., Bhandari, S., Fraser, D., Kalra, P., Kon, S.P., Mccafferty, K., Mikhail, A., Alvarado, O.P., Anderson, R., Andrawis, N.S., Arif, A., Benjamin, S.A., Bueso, G., Busch, R.S., Carr, K.W., Crawford, P., Daboul, N., De La Calle, G.M., Delgado, B., Earl, J., El-Shahawy, M.A., Graf, R.J., Greenwood, G., Guevara, A., Wendland, E.M., Mayfield, R.K., Montero, M., Morin, D.J., Narayan, P., Numrungroad, V., Reddy, A.C., Reddy, R., Samson, M.B., Trejo, R., Butcher, M.B., Wise, J.K., Zemel, L.R., Raikhel, M., Weinstein, D., Hernandez, P., Wynne, A., Khan, B.V., Sterba, G.A., Jamal, A., Ross, D., Rovner, S.F., Tan, A., Ovalle, F., Patel, R.J., Talano, J., Patel, D.R., Burgner, A., Aslam, N., Elliott, M., Goral, S., Jovanovich, A., Manley, J.A., Umanath, K., Waguespack, D., Weiner, D., Yu, M., Schneider, L., Jalal, D., Le, T., Nguyen, N., Nguyen, H., Nguyen, D., Nguyen, V., Do, T., Chu, P., Ta, D., Tran, N., Pham, B., Pfeffer, Marc A., Pocock, Stuart, Swedberg, Karl, Rouleau, Jean L., Chaturvedi, Nishi, Ivanovich, Peter, Levey, Andrew S., Christ-Schmidt, Heidi, Held, Claes, Christersson, Christina, Mann, Johannes, Varenhorst, Christoph, Cherney, David, Postmus, Douwe, Stefánsson, Bergur V., Chertow, Glenn M., Dwyer, Jamie P., Kosiborod, Mikhail, McMurray, John J.V., Sjöström, C. David, and Toto, Robert D.

Published
2022
Full Text
View/download PDF

6. 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
Full Text
View/download PDF

9. Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool

Author

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., 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., Bellur, S., Mazzucco, G., Giannakakis, C., Honsova, E., Sundelin, B., Di Palma, A.M., Gutiérrez, 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., 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, 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., Barbour, Sean J., Canney, Mark, Coppo, Rosanna, Zhang, Hong, Liu, Zhi-Hong, Suzuki, Yusuke, Matsuzaki, Keiichi, Katafuchi, Ritsuko, Induruwage, Dilshani, Er, Lee, Reich, Heather N., Feehally, John, Barratt, Jonathan, and Cattran, Daniel C.

Published
2020
Full Text
View/download PDF

15. Effects of Sacubitril/Valsartan Versus Irbesartan in Patients With Chronic Kidney Disease: A Randomized Double-Blind Trial

Author

Haynes, Richard, Judge, Parminder K., Staplin, Natalie, Herrington, William G., Storey, Benjamin C., Bethel, Angelyn, Bowman, Louise, Brunskill, Nigel, Cockwell, Paul, Hill, Michael, Kalra, Philip A., McMurray, John J.V., Taal, Maarten, Wheeler, David C., Landray, Martin J., Baigent, Colin, Haynes, R., Judge, P.K., Staplin, N., Herrington, W.G., Storey, B.C., Bethel, A., Bowman, L., Brunskill, N., Cockwell, P., Hill, M., Kalra, P.A., McMurray, J.J., Taal, M., Wheeler, D.C., Landray, M.J., Baigent, C., Baigent, C., Haynes, R., Landray, M.J., Dayanandan, R., Baxter, A., Staplin, N., Bethel, A., Bowman, L., Brunskill, N., Cockwell, P., Herrington, W.G., Hill, M., Judge, P.K., Kalra, P.A., Knott, C., McMurray, J.J.V., Murphy, K., Taal, M., Wheeler, D.C., Wheatley, K., Emberson, J., Tomson, C., Roderick, P., Clark, L., Annand, J., Marks, A., Rose, H., Taal, M., Brear, T., Havill, L., McKinnell, J., Melbourne, S., Shardlow, A., Smith, J., Stone, C., Rowe, P., Connor, A., Wooding, J., Taylor, J., Bough, L., Purse, K., Wignall, S., Winter-Goodwin, B., Brunskill, N., Bailey, B., Barratt, J., Bielecka, E., McCartney, M., Hutchison, A., Asari, A., Waring, D., Sajith, R., Walton, H., Mikhail, A., Hilldrup, I., Latif, F., Shrivastava, R., Nicholas, J., Byrne, T., Sandhu, K.S., Tan, B.K., Ward, J., Whistance-Smith, D., Khwaja, A., Jackson, Y., Kawar, B., Middle, J., Sorrell, J., Byrne, C., Brand, S., McHaffie, E., Haynes, R., Crosbie, S., Judge, P.K., Lafferty, K., Ruse, S., Sharples, E., Storey, B.C., Sampson, A., Kirk, A., Lewis, R., Vinall, L., Watkins, L., Williams, F., Cockwell, P., Anderson, N., Dutton, M., Ferro, C., Fifer, L., Smith, S., Stringer, S., Bhandary, N., Alchi, B., Foxton, J., Jones, L., D’Souza, R., Harrison, D., Heddon, S., Wheeler, D.C., Caplin, B., Damian, E., Sobande, T., Davies, S., Edwards, C., Matthews, C., Plaza, M., Reddy, S., Kalra, P.A., Chiu, D., Haydock, L., Kershaw, M., Wilson, C., Vassallo, D., Methven, S., Bowles, J., Collins, E., Dawson, S., Power, A., Kardasz, S., Laven, C., Wroe, C., Eardley, K., Donaldson, D., Tonks, L., Ayub, W., Evans, G., Hewins, S., Fraser, D., Bagshawe, J., Foxwell, D., Williams, A., Border, D., Birch, S., Griffiths, L., Jones, C., McCullough, K., Molyneux, R., and Richardson, D.

Published
2018
Full Text
View/download PDF

18. Genotyping Cyclospora cayetanensis from multiple outbreak clusters with an emphasis on a cluster linked to bagged salad mix - United States, 2020

Author

Barratt, J, Ahart, L, Rice, M, Houghton, K, Richins, T, Cama, V, Arrowood, M, Qvarnstrom, Y, and Straily, A

Subjects
Genotype, 06 Biological Sciences, 11 Medical and Health Sciences, Humans, Salads, Cyclosporiasis, Microbiology, United States, Cyclospora, Disease Outbreaks
Abstract

Cyclosporiasis is a diarrheal illness caused by the food-borne parasite Cyclospora cayetanensis. Annually reported cases have been increasing in the United States prompting development of genotyping tools to aid cluster detection. A recently developed Cyclospora genotyping system based on eight genetic markers was applied to clinical samples collected during the cyclosporiasis peak-period of 2020, facilitating assessment of its epidemiologic utility. While the system performed well and helped inform epidemiological investigations, inclusion of additional markers to improve cluster detection was supported. Consequently, investigations have commenced to identify additional markers to enhance performance.

Published
2021

19. Investigation of US Cyclospora cayetanensis outbreaks in 2019 and evaluation of an improved Cyclospora genotyping system against 2019 cyclosporiasis outbreak clusters

Author

Barratt, J, Houghton, K, Richins, T, Straily, A, Threlkel, R, Bera, B, Kenneally, J, Clemons, B, Madison-Antenucci, S, Cebelinski, E, Whitney, BM, Kreil, KR, Cama, V, Arrowood, MJ, and Qvarnstrom, Y

Subjects
Molecular Epidemiology, Genotype, Genotyping Techniques, Epidemiology, Clinical Laboratory Techniques, DNA, Protozoan, United States, 1117 Public Health and Health Services, Cyclospora, Disease Outbreaks, Feces, Cluster Analysis, Humans, Cyclosporiasis
Abstract

Cyclosporiasis is an illness characterised by watery diarrhoea caused by the food-borne parasite Cyclospora cayetanensis. The increase in annual US cyclosporiasis cases led public health agencies to develop genotyping tools that aid outbreak investigations. A team at the Centers for Disease Control and Prevention (CDC) developed a system based on deep amplicon sequencing and machine learning, for detecting genetically-related clusters of cyclosporiasis to aid epidemiologic investigations. An evaluation of this system during 2018 supported its robustness, indicating that it possessed sufficient utility to warrant further evaluation. However, the earliest version of CDC's system had some limitations from a bioinformatics standpoint. Namely, reliance on proprietary software, the inability to detect novel haplotypes and absence of a strategy to select an appropriate number of discrete genetic clusters would limit the system's future deployment potential. We recently introduced several improvements that address these limitations and the aim of this study was to reassess the system's performance to ensure that the changes introduced had no observable negative impacts. Comparison of epidemiologically-defined cyclosporiasis clusters from 2019 to analogous genetic clusters detected using CDC's improved system reaffirmed its excellent sensitivity (90%) and specificity (99%), and confirmed its high discriminatory power. This C. cayetanensis genotyping system is robust and with ongoing improvement will form the basis of a US-wide C. cayetanensis genotyping network for clinical specimens.

Published
2021

20. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status

Author

Lyons, P. A., Peters, J. E., Alberici, F., Liley, J., Coulson, R. M. R., Astle, W., Baldini, C., Bonatti, F., Cid, María Cinta, Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D. R. W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M. A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G. A., Rewerska, B., Schett, George, Sinico, R. A., Szczeklik, W., Tesar, Vladimir, Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A. S., Bruce, I., Clarkson, M., Conlon, N., DasGupta, B., Doulton, T. W. R., Espígol-Frigolé, Georgina, Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernández Rodríguez, José, Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A. A., Marguerie, C., Maritati, F., Marvisi, C., McHugh, N. J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, Leonid, Pesci, Alberto, Prieto-Gonzalez, S., Ramentol-Sintas, Marc, Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans, Roser, Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R. A., Vaglio, A., Holle, J. U., Wallace, C., Smith, K. G. C., Universitat Autònoma de Barcelona, Lyons, P. A., Peters, J. E., Alberici, F., Liley, J., Coulson, R. M. R., Astle, W., Baldini, C., Bonatti, F., Cid, M. C., Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D. R. W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M. A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G. A., Rewerska, B., Schett, G., Sinico, R. A., Szczeklik, W., Tesar, V., Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A. S., Bruce, I., Clarkson, M., Conlon, N., Dasgupta, B., Doulton, T. W. R., Espigol-Frigole, G., Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernandez-Rodriguez, J., Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A. A., Marguerie, C., Maritati, F., Marvisi, C., Mchugh, N. J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, L., Pesci, A., Prieto-Gonzalez, S., Ramentol-Sintas, M., Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans-Laque, R., Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R. A., Vaglio, A., Holle, J. U., Wallace, C., Smith, K. G. C., Lyons, P, Peters, J, Alberici, F, Liley, J, Coulson, R, Astle, W, Baldini, C, Bonatti, F, Cid, M, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, D, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, M, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramierez, G, Rewerska, B, Schett, G, Sinico, R, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, A, Bruce, I, Clarkson, M, Conlon, N, Dasgupta, B, Doulton, T, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, A, Marguerie, C, Maritati, F, Marvisi, C, Mchugh, N, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, R, Vaglio, A, Holle, J, Wallace, C, Smith, K, and United Kingdom Research and Innovation

Subjects
0301 basic medicine, Candidate gene, Antineutrophil Cytoplasmic, General Physics and Astronomy, Genome-wide association study, Autoimmunity, Genome-wide association studies, 0302 clinical medicine, Rheumatic diseases, immune system diseases, Eosinophilic, Eosinophilia, lcsh:Science, education.field_of_study, Multidisciplinary, Genome-wide association, eosinophilic granulomatosis with polyangiitis, ANCA status, 3. Good health, medicine.symptom, Vasculitis, Granulomatosis with polyangiitis, Antibodies, Antineutrophil Cytoplasmic, Eosinophils, Genetic Association Studies, Granulomatosis with Polyangiitis, Humans, Mendelian Randomization Analysis, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, European Vasculitis Genetics Consortium, Science, Population, General Biochemistry, Genetics and Molecular Biology, Article, Antibodies, 03 medical and health sciences, medicine, Immunogenetics, education, Rheumatology and Autoimmunity, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, Reumatologi och inflammation, business.industry, General Chemistry, medicine.disease, respiratory tract diseases, 030104 developmental biology, Immunology, EGPA, HLA, ANCA, genetics, lcsh:Q, business
Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA., Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).

Published
2019

25. 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

26. 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. 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. Bellur, S. Mazzucco, G. Giannakakis, C. Honsova, E. Sundelin, B. Di Palma, A.M. Gutiérrez, 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. International IgA Nephropathy Network

Abstract

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,1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR). Results During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups. Conclusions Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints. Copyright © 2021 by the American Society of Nephrology.

Published
2021

29. 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

30. Detecting sequence variants in clinically important protozoan parasites

Author

Calarco L, Barratt J, and Ellis J

Subjects
Leishmania, Plasmodium, Protozoan Infections, Trypanosoma cruzi, Drug Resistance, Computational Biology, Genetic Variation, High-Throughput Nucleotide Sequencing, Mycology & Parasitology, Sequence Analysis, DNA, DNA, Protozoan, Polymorphism, Single Nucleotide, Genetics, Population, 0605 Microbiology, 0608 Zoology, 0707 Veterinary Sciences, Animals, Humans, Parasites, Toxoplasma, Genome, Protozoan, Phylogeny
Abstract

Second and third generation sequencing methods are crucial for population genetic studies, and variant detection is a popular approach for exploiting this sequence data. While mini- and microsatellites are historically useful markers for studying important Protozoa such as Toxoplasma and Plasmodium spp., detecting non-repetitive variants such as those found in genes can be fundamental to investigating a pathogen's biology. These variants, namely single nucleotide polymorphisms and insertions and deletions, can help elucidate the genetic basis of an organism's pathogenicity, identify selective pressures, and resolve phylogenetic relationships. They also have the added benefit of possessing a comparatively low mutation rate, which contributes to their stability. However, there is a plethora of variant analysis tools with nuanced pipelines and conflicting recommendations for best practise, which can be confounding. This lack of standardisation means that variant analysis requires careful parameter optimisation, an understanding of its limitations, and the availability of high quality data. This review explores the value of variant detection when applied to non-model organisms such as clinically important protozoan pathogens. The limitations of current methods are discussed, including special considerations that require the end-users' attention to ensure that the results generated are reproducible, and the biological conclusions drawn are valid.

Published
2020

31. Identifying outcomes important to patients with glomerular disease and their caregivers

Author

Carter, S.A. Gutman, T. Logeman, C. Cattran, D. Lightstone, L. Bagga, A. Barbour, S.J. Barratt, J. Boletis, J. Caster, D. Coppo, R. Fervenza, F.C. Floege, J. Hladunewich, M. Hogan, J.J. Richard Kitching, A. Lafayette, R.A. Malvar, A. Radhakrishnan, J. Rovin, B.H. Scholes-Robertson, N. Trimarchi, H. Zhang, H. Azukaitis, K. Cho, Y. Viecelli, A.K. Dunn, L. Harris, D. Johnson, D.W. Kerr, P.G. Laboi, P. Ryan, J. Shen, J.I. Ruiz, L. Wang, A.Y.-M. Lee, A.H.K. Fung, S. Tong, M.K.-H. Teixeira-Pinto, A. Wilkie, M. Alexander, S.I. Craig, J.C. Tong, A.

Abstract

Background and objectives Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices. Design, setting, participants, & measurements We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States. Participants identified, discussed, and ranked outcomes in focus groups using the nominal group technique; a relative importance score (between zero and one) was calculated. Qualitative data were analyzed thematically. Results Across 16 focus groups, 134 participants (range, 19–85 years old; 51%women), including 101 patients and 33 caregivers, identified 58 outcomes. The ten highest-ranked out comes were kidney function(importance score of 0.42), mortality (0.29), need for dialysis or transplant (0.22), life participation (0.18), fatigue (0.17), anxiety (0.13), family impact (0.12), infection and immunity (0.12), ability to work (0.11), and BP (0.11). Three themes explained the reasons for these rankings: Constraining day-to-day experience, impaired agency and control over health, and threats to future health and family. Conclusions Patients with glomerular disease and their caregivers highly prioritize kidney health and survival, but they also prioritize life participation, fatigue, anxiety, and family impact. © 2020 by the American Society of Nephrology.

Published
2020

44. 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. Gomá, M. Gröne, H.-J. Gutiérrez, 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. 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. 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. Ferrario, F. 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. 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. Kilicaslan, I.

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. © 2018 The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Published
2019

45. 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

46. 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

Catalog

Books, media, physical & digital resources
See catalog results