2019 · NEW ENGLAND JOURNAL OF MEDICINE

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., Cannon, C. P., Capuano, G., Chu, P. -L., De Zeeuw, D., Greene, T., Levin, A., Pollock, C., Wheeler, D. C., Yavin, Y., Zhang, H., Zinman, B., Meininger, G., Brenner, B. M., Mahaffey, K. W., McGuire, Darren K., Holman, Rury, Home, Philip, Scharfstein, Dan, Parfrey, Patrick, Shahinfar, Shahnaz, August, Phyllis, Chang, Tara, Sinha, Arjun D., Januzzi, James, Kolansky, Daniel, Amerena, John, Hillis, Graham, Gorelick, Philip, Kissela, Brett, Kasner, Scott, Lindley, Richard, Fulcher, Greg, Ounadjela, Souhila, Hufert, Karina, von Ingersleben, Gabriele, Gaglia, Jason, Harris, Ronald, Hudson, Margo, Turchin, Alexander, Cheifetz, Adam, Sheth, Sunil, Feuerstein, Joseph, Cohen, Samuel, Li, Nicole, Kolesnyk, Inna, Aizenberg, Diego, Pecoits-Filho, Roberto, Cherney, David, Obrador, Gregorio, Chertow, Glenn, Hawley, Carmel, Ji, Linong, Wada, Takashi, Jha, Vivekanand, Lim, Soo Kun, Lim-Abrahan, Mary Anne, Santos, Florence, Chae, Dong-Wan, Hwang, Shang-Jyh, Vazelov, Evgueniy, Rychlik, Ivan, Hadjadj, Samy, Krane, Vera, Rosivall, Laszlo, De Nicola, Luca, Dreval, Alexander, Nowicki, Michal, Schiller, Adalbert, Distiller, Larry, Gorriz, Jose L., Kolesnyk, Mykola, Morren, Fran, Goykhman, Svetlana, David, Caryl, Yost, Lori, Wang, Holly, Hettiarachchi, Manthi, Thimmaiah, Ramesh, Koppolu, Deepak, George, Sini, Schmidt, Manuela, Ignjatovic, Jelena, Chapin, Lincoln, Travis, Kim, Destree, Martine, Sood, Vivek, Coffee, Laura, De Brouwer, Kati, Zaviriukha, Viktor, Starzec, Agnieszka, Koizumi, Masahiro, Lin, Grace, Chen, Evaly, Lin, Peggy, Leia, Chen, Mascaro, Debbie, Amigo, Anabella, Limos, Ana, Abrahamsen, Ingrid, Jaffer, Sara, Ahuad Guerrero, Rodolfo Andres, Aizenberg, Diego, Pablo Albisu, Juan, Alvarisqueta, Andres, Bartolacci, Ines, Alberto Berli, Mario, Bordonava, Anselmo, Calella, Pedro, Cecilia Cantero, Maria, Rodolfo Cartasegna, Luis, Cercos, Esteban, Cecilia Coloma, Gabriela, Colombo, Hugo, Commendatore, Victor, Cuadrado, Jesus, Alberto Cuneo, Carlos, Maria Cusumano, Ana, Guillermo Douthat, Walter, Dario Dran, Ricardo, Farias, Eduardo, Florencia Fernandez, Maria, Finkelstein, Hernan, Fragale, Guillermo, Osvaldo Fretes, Jose, Horacio Garcia, Nestor, Gastaldi, Anibal, Gelersztein, Elizabeth, Archibaldo Glenny, Jorge, Pablo Gonzalez, Joaquin, Gonzalez Colaso, Patricia del Carmen, Goycoa, Claudia, Cristian Greloni, Gustavo, Guinsburg, Adrian, Hermida, Sonia, Isaias Juncos, Luis, Isabel Klyver, Maria, Kraft, Florencia, Krynski, Fernando, Virginia Lanchiotti, Paulina, Leon de la Fuente, Ricardo Alfonso, Marchetta, Nora, Mele, Pablo, Nicolai, Silvia, Antonio Novoa, Pablo, Ines Orio, Silvia, Otreras, Fabian, Oviedo, Alejandra, Raffaele, Pablo, Hector Resk, Jorge, Rista, Lucas, Rodriguez Papini, Nelson, Sala, Jorgelina, Carlos Santos, Juan, Beatriz Schiavi, Lilia, Sessa, Horacio, Casabella, Tomas Smith, Ulla, Maria Rosa, Valdez, Maria, Vallejos, Augusto, Villarino, Adriana, Esther Visco, Virginia, Wassermann, Alfredo, Javier Zaidman, Cesar, Cheung, Ngai Wah, Droste, Carolyn, Fraser, Ian, Johnson, David, Mah, Peak Mann, Nicholls, Kathy, Packham, David, Proietto, Joseph, Roberts, Anthony, Roger, Simon, Tsang, Venessa, Raduan, Roberto Abrao, Alves da Costa, Fernando Augusto, Amodeo, Celso, Andreotti Turatti, Luiz Alberto, Bregman, Rachel, Camelo Sanches, Fernanda Cristina, Canani, Luis Henrique, Chacra, Antonio Roberto, Cunha Borges, Joao Lindolfo, Cunha Vencio, Sergio Alberto, da Silva Franco, Roberto Jorge, d'Avila, Domingos, Portes, Evandro de Souza, de Souza, Pedro, Deboni, Luciane Monica, Fraige Filho, Fadlo, Geloneze Neto, Bruno, Gomes, Marcus, Kohara, Suely Keiko, Keitel, Elizete, Kerr Saraiva, Jose Francisco, Kurtz Lisboa, Hugo Roberto, de Carvalho Contieri, Fabiana Loss, Milagres, Rosângela, Montenegro Junior, Renan, de Brito, Claudia Moreira, Hissa, Miguel Nasser, Nazario Sabbag, Angela Regina, Noronha, Irene, Panarotto, Daniel, Pecoits Filho, Roberto, Pereira, Márcio Antonio, Saporito, Wladmir, Scotton, Antonio Scafuto, Schuch, Tiago, de Almeida, Roberto Simoes, Ramos, Cassio Slompo, Felicio, Joao Soares, Thome, Fernando, Tibes Hachmann, Jean Carlo, Yamada, Sergio, Hayashida, Cesar Yoiti, Zanata Petry, Tarissa Beatrice, Zanella, Maria Teresa, Andreeva, Viktoria, Angelova, Angelina, Dimitrov, Stefan, Genadieva, Veselka, Genova-Hristova, Gabriela, Hristozov, Kiril, Kamenov, Zdravko, Koundurdjiev, Atanas, Lozanov, Lachezar, Margaritov, Viktor, Nonchev, Boyan, Rangelov, Rangel, Shinkov, Alexander, Temelkova, Margarita, Velichkova, Ekaterina, Yakov, Andrian, Aggarwal, Naresh, Aronson, Ronnie, Bajaj, Harpreet, Cherney, David, Chouinard, Guy, Conway, James, Cournoyer, Serge, DaRoza, Gerald, De Serres, Sacha, Dube, Francois, Goldenberg, Ronald, Gupta, Anil, Gupta, Milan, Henein, Sam, Khandwala, Hasnain, Leiter, Lawrence, Madore, Francois, McMahon, Alan, Muirhead, Norman, Pichette, Vincent, Rabasa-Lhoret, Remi, Steele, Andrew, Tangri, Navdeep, Torshizi, Ali, Woo, Vincent, Zalunardo, Nadia, Fernandez Montenegro, Maria Alicia, Godoy Jorquera, Juan Gonzalo, Medina Farina, Marcelo, Saavedra Gajardo, Victor, Vejar, Margarita, Chen, Nan, Chen, Qinkai, Gan, Shenglian, Kong, Yaozhong, Li, Detian, Li, Wenge, Li, Xuemei, Lin, Hongli, Liu, Jian, Lu, Weiping, Mao, Hong, Ren, Yan, Song, Weihong, Sun, Jiao, Sun, Lin, Tu, Ping, Wang, Guixia, Yang, Jinkui, Yin, Aiping, Yu, Xueqing, Zhao, Minghui, Zheng, Hongguang, Accini Mendoza, Jose Luis, Arcos, Edgar, Avendano, Jorge, Andres Diaz Ruiz, Jorge Ernesto, Garcia Ortiz, Luis Hernando, Gonzalez, Alexander, Hernandez Triana, Eric, Diego Higuera, Juan, Malaver, Natalia, Molina de Salazar, Dora Ines, Rosero, Ricardo, Terront Lozano, Monica Alexandra, Valderrama Cometa, Luis, Valenzuela, Alex, Vargas Alonso, Ruben Dario, Villegas, Ivan, Yupanqui, Hernan, Bartaskova, Dagmar, Barton, Petr, Belobradkova, Jana, Dohnalova, Lenka, Drasnar, Tomas, Ferkl, Richard, Halciakova, Katarina, Klokocnikova, Vera, Kovar, Richard, Lastuvka, Jiri, Lukac, Martin, Pesickova, Satu, Peterka, Karel, Pumprla, Jiri, Rychlik, Ivan, Saudek, Frantisek, Tesar, Vladimir, Valis, Martin, Weiner, Pavel, Zemek, Stanislav, Alamartine, Eric, Borot, Sophie, Cariou, Bertrand, Dussol, Bertrand, Fauvel, Jean-Pierre, Gourdy, Pierre, Klein, Alexandre, Le Meur, Yannick, Penfornis, Alfred, Roussel, Ronan, Saulnier, Pierre-Jean, Thervet, Eric, Zaoui, Philippe, Burst, Volker, Faghih, Markus, Faulmann, Grit, Haller, Hermann, Jerwan-Keim, Reinhold, Maxeiner, Stephan, Paschen, Bjoern, Plassmann, Georg, Rose, Ludger, Gonzalez Orellana, Ronaldo Arturo, Paul Haase, Franklin, Moreira Diaz, Juan Pablo, Ramirez Roca, Luis Alberto, Sanchez Arenales, Jose Antonio, Sanchez Polo, Jose Vicente, Turcios Juarez, Erick, Csecsei, Gyongyi, Csiky, Botond, Danos, Peter, Deak, Laszlo, Dudas, Mihaly, Harcsa, Eleonora, Keltai, Katalin, Keresztesi, Sandor, Kiss, Krisztian, Konyves, Laszlo, Major, Lajos, Mileder, Margit, Molnar, Marta, Mucsi, Janos, Oroszlan, Tamas, Ory, Ivan, Paragh, Gyorgy, Peterfai, Eva, Petro, Gizella, Revesz, Katalin, Takacs, Robert, Vangel, Sandor, Vasas, Szilard, Zsom, Marianna, Abraham, Oomman, Bhushan, Raju Sree, Deepak, Dewan, Edwin, Fernando M., Gopalakrishnan, Natarajan, Gracious, Noble, Hansraj, Alva, Jain, Dinesh, Keshavamurthy, C. B., Khullar, Dinesh, Manisha, Sahay, Peringat, Jayameena, Prasad, Narayan, Satyanarayana, Rao K., Sreedhar, Reddy, Sreelatha, Melemadathil, Sudhakar, Bhimavarapu, Vyasam, Ramesh Chandra, Bonadonna, Riccardo, Castellino, Pietro, Ceriello, Antonio, Chiovato, Luca, De Cosmo, Salvatore, De Nicola, Luca, Derosa, Giuseppe, Di Carlo, Alberto, Di Cianni, Graziano, Frasca, Giovanni, Fuiano, Giorgio, Gambaro, Giovanni, Garibotto, Giacomo, Giorda, Carlo, Malberti, Fabio, Mandreoli, Marcora, Mannucci, Edoardo, Orsi, Emanuela, Piatti, Piermarco, Santoro, Domenico, Sasso, Ferdinando Carlo, Serviddio, Gaetano, Stella, Andrea, Trevisan, Roberto, Veronelli, Anna Maria, Zanoli, Luca, Akiyama, Hitoshi, Aoki, Hiromi, Asano, Akimichi, Iitsuka, Tadashi, Kajiyama, Shizuo, Kashine, Susumu, Kawada, Toshio, Kodera, Takamoto, Kono, Hiroshi, Koyama, Kazunori, Kumeda, Yasuro, Miyauchi, Shozo, Mizuyama, Kazuyuki, Niiya, Tetsuji, Oishi, Hiroko, Ota, Satoshi, Sakakibara, Terue, Takai, Masahiko, Tomonaga, Osamu, Tsujimoto, Mitsuru, Wada, Takashi, Wakasugi, Masakiyo, Wakida, Yasushi, Watanabe, Takayuki, Yamada, Masayo, Yanagida, Kazuhiro, Yanase, Toshihiko, Yumita, Wataru, Gaupsiene, Egle, Kozloviene, Dalia, Navickas, Antanas, Urbanaviciene, Egle, Ghani, Rohana Abdul, Kadir, Khalid Abdul, Ali, Norsiah, Yusof, Mohd Daud Che, Gan, Chye Lee, Ismail, Mastura, Kong, Wei Yen, Lam, Swee Win, Lee, Li Yuan, Lim, Soo Kun, Loh, Chek Loong, Manocha, Anita Bhajan, Ng, Kee Sing, Ahmad, Nik Nur Fatnoon Nik, Ratnasingam, Vanassa, Bin Shudim, Saiful Shahrizal, Vengadasalam, Paranthaman, Abraira Munoz, Luis David, Alpizar Salazar, Melchor, Baas Cruz, Juan, Burgos Soto, Mario, Chevaile Ramos, Jose, Chew Wong, Alfredo, Correa Rotter, Jose Ricardo, Diaz Escalante, Tonatiu, Enriquez Sosa, Favio Edmundo, Flores Lozano, Fernando, Flota Cervera, Luis Fernando, Frenk Baron, Paul, Garcia Ballesteros, Cecilia, Gomez Rangel, Jose David, Herrera Jimenez, Luis Enrique, Irizar Santana, Sergio Saul, Jimenez Flores, Fernando, Laviada Molina, Hugo, Luna Ceballos, Rosa Isela, del Campo Blanco, Belia Martin, Morales Franco, Guadalupe, Moreno Loza, Oscar Tarsicio, Mustieles Rocha, Cynthia, Obrador Vera, Gregorio, Orozco Castellanos, Ricardo, Peralta Calcaneo, Juan, Reyes Rosano, Miguel Angel, Rodriguez Pattzi, Hiromi, Rosas Guzman, Juan, Rucker Joerg, Isabel Erika, Saavedra Sanchez, Sandra Berenice, Sanchez Mijangos, Jose Hector, Serrano Sanson, Pablo, Tamayo y Orozco, Juan Alfredo, Tellez Chavez, Eloisa, Valdes Cepeda, Alejandro, Venegas Carrillo, Luis, Villagordoa Mesa, Juan, Zamarripa Escobedo, Rolando, Baker, John, Noonan, Paul, Scott, Russell, Walker, Robert, Watson, Edward, Williams, Michael, Young, Simon, Abejuela, Zaynab, Agra, Jeimeen, Aquitania, Grace, Caringal, Clodoaido, Comia, Rhea Severina, Delos Santos, Lalaine, Gomez, Olivert, Jimeno, Cecilia, Tan, Gerry, Tolentino, Marsha, Yao, Christy, Yap, Yvette Ethel, Ygpuara, Maria Dovie Lallaine, Bijata-Bronisz, Renata, Hotlos, Lucyna, Januszewicz, Andrzej, Kaczmarek, Barbara, Kaminska, Anna, Lazuka, Lech, Madej, Andrzej, Mazur, Stanislaw, Mlodawska-Choluj, Dorota, Orlowska-Kowalik, Grazyna, Popenda, Grazyna, Rewerska, Barbara, Sowinski, Dariusz, Angelescu, Liliana Monica, Anghel, Veronica, Avram, Rodica-Ioana, Busegeanu, Mihaela-Magdalena, Cif, Adriana, Cosma, Dana, Crisan, Carmen, Demian, Luiza Despina, Ferariu, Ioana Emilia, Halmagyi, Ildiko, Hancu, Nicolae, Munteanu, Mircea, Negru, Doru, Onaca, Adriana Gabriela, Petrica, Ligia, Popa, Amorin Remus, Ranetti, Aurelian-Emil, Serafinceanu, Cristian, Toarba, Cristina, Agafyina, Alina, Barbarash, Olga, Barysheva, Olga, Chizhov, Daniil, Dobronravov, Vladimir, Glinkina, Irina, Grineva, Elena, Khirmanov, Vladimir, Kolmakova, Elena, Koroleva, Tatiana, Kvitkova, Liudmila, Marasaev, Viacheslav, Mkrtumyan, Ashot, Morugova, Tatiana, Nagibovich, Galina, Nagibovich, Oleg, Nedogoda, Sergei, Osipova, Irina, Raskina, Tatiana, Samoylova, Yulia, Sazonova, Olga, Shamkhalova, Minara, Shutemova, Elena, Shwartz, Yuriy, Uriasyev, Oleg, Vorobyev, Sergey, Zateyshchikova, Anna, Zateyshshikov, Dmitry, Zykova, Tatyana, Antic, Slobodan, Djordjevic, Miodrag, Kendereski, Aleksandra, Lalic, Katarina, Lalic, Nebojsa, Popovic-Radinovic, Vesna, Babikova, Jana, Benusova, Olga, Buganova, Ingrid, Culak, Jan, Dzupina, Andrej, Dzuponova, Jana, Fulop, Peter, Ilavska, Adriana, Martinka, Emil, Ochodnicka, Zuzana, Pella, Daniel, Smatanova, Iveta, Ahmed, Fayzal, Badat, Aysha, Breedt, Johannes, Distiller, Lawrence, Govender, Vimladhevi, Govender, Ravendran, Joshi, Mukesh, Jurgens, Jaco, Latiff, Gulam, Lombard, Landman, Mookadam, Mohamed, Ngcakani, Nomangesi, Nortje, Hendrik, Oosthuizen, Helena, Pillay-Ramaya, Larisha, Prozesky, Hans, Reddy, Jeevren, Rheeder, Paul, Seeber, Mary, Cho, Young Min, Jeong, In-Kyung, Kim, Sin Gon, Kim, Yeong Hoon, Kwon, Hyuk-Sang, Kwon, Min Jeong, Lee, Byung-Wan, Lee, JungEun, Lee, Moon-Kyu, Nam, Moon-Suk, Oh, Kook-Hwan, Park, Cheol-Young, Park, Sun-Hee, Yoon, Kun Ho, Alvarez Garcia, Pere, Asmarats Mercadal, Luis, Barrios, Clara, Cereto Castro, Fernando, Cigarran Guldris, Secundino, Dominguez Lopez, Marta, Egido de los Rios, Jesus, Fernandez Fresnedo, Gema, Galan Serrano, Antonio, Garcia, Isabel, Gonzalez Martinez, Francisco Javier, Jodar Gimeno, Jose Esteban, Lopez Mendoza, Manuel, Malek Marin, Tamara, Morales Portillo, Cristobal, Munar Vila, Maria Antonia, Munoz Torres, Manuel, Nieto Iglesias, Javier, Pantoja Perez, Jonay, Perez Vera, Merce, Portoles Perez, Jose Maria, Quesada Simon, Maria Angustias, Simo Canonge, Rafael, Soto Gonzalez, Alfonso, Terns Riera, Manel, Tinahones Madueno, Francisco Jose, Velo Plaza, Mercedes, Chang, Chwen-Tzuei, Chuang, Lee-Ming, Hsia, Te-Lin, Hsieh, Chang-Hsun, Lin, Chih-Ching, Lu, Yung-Chuan, Sheu, Wayne H-H, Barna, Olga, Bilyk, Svitlana D., Botsyurko, Volodymyr, Dudar, Iryna, Fushtey, Ivan, Godlevska, Olga, Golovchenko, Oleksandr, Gyrina, Olga, Kazmirchuk, Anatoliy, Komisarenko, Iuliia, Korzh, Oleksii, Kravchun, Nonna, Legun, Oleg, Mankovskyy, Borys, Martynyuk, Liliya, Mostovoy, Yuriy, Pashkovska, Nataliia, Pererva, Larysa, Pertseva, Tetyana, Samoylov, Oleksandr, Smirnov, Ivan, Svyshchenko, Yevgeniya, Tomashkevych, Halyna, Topchii, Ivan, Tryshchuk, Nadiya, Tseluyko, Vira, Vizir, Vadym, Vlasenko, Maryna, Zlova, Tetiana, Zub, Liliia, Abusnana, Salah, Railey, Mohamed, Abouglila, Kamal, Ainsworth, Paul, Ali, Zishan, Arutchelvam, Vijayaraman, Barnard, Maria, Bellary, Srikanth, Davies, Emyr, Davies, Mark, Davies, Simon, Dawson, Alison, El Kossi, Mohsen, English, Patrick, Fraser, Donald, Gnudi, Luigi, Gunstone, Anthony, Hall, Timothy, Hanif, Wasim, Jackson, Alan, Johnson, Andrew, Joseph, Franklin, Krishnan, Singhan, Kumwenda, Mick, MacDougall, Iain, Nixon, Paul, O'Hare, Joseph, Philip, Sam, Ramtoola, Shenaz, Saxena, Manish, Sennik, Davesh, Simon, Godwin, Singh, Baldev, Stephens, Jeffrey, Strzelecka, Anna, Symonds, Rehan, Turner, Wayne, Wahba, Mona, Wakeling, John, Wheeler, David, Winocour, Peter, Abdallah, Joseph, Abdullah, Raied, Abramowitz, Matthew, Acosta, Idalia, Aiello, Joseph, Akright, Laura, Akyea-Djamson, Ayim, Alappan, Rajendran, Alicic, Radica, Al-Karadsheh, Amer, Allison, Dale Crawford, Arauz-Pacheco, Carlos, Arfeen, Shahabul, Arif, Ahmed, Arvind, Moogali, Atray, Naveen, Awad, Ahmed, Barnhill, Peggy, Barranco, Elizabeth, Barrera, Carlos, Beacom, Matthew, Behara, Venkata, Belo, Diogo, Bentley-Lewis, Rhonda, CREDENCE Trial Investigators

Journal
NEW ENGLAND JOURNAL OF MEDICINE
Année
2019
Volume
380
Numéro
24
Pages
2295-2306
Mois
JUN 13
DOI
10.1056/NEJMoa1811744

Abstract

Background Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. Methods In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m(2) of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m(2)), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. Results The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. Conclusions In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.)

Lire l'article complet