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Devuyst, Olivier

https://orcid.org/0000-0003-3744-4767

Mayo Clinic

University of Zurich

Citations 10

The Effect of Tolvaptan on BP in Polycystic Kidney Disease: A Post Hoc Analysis of the TEMPO 3:4 Trial
Heida, Judith E. , Gansevoort, Ron T. , Torres, Vicente E. , Devuyst, Olivier , Perrone, Ronald D. , Lee, Jennifer , Li, Hui , Ouyang, John , Chapman, Arlene B., Torres, Vicente E , Torres, Vicente E , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767

Journal of the American Society of Nephrology | April 22, 2021 | Volume: 32 | Issue: 7 | Pages: 1801-1812

10.1681/asn.2020101512 Get It

Significance Statement Patients with autosomal dominant polycystic kidney disease are treated with tolvaptan, a V2 receptor antagonist, to slow progression toward ESKD. In theory, tolvaptan could have both BP-increasing and BP-decreasing effects. To investigate the magnitude and time course of the effect of tolvaptan use on BP, the authors conducted a post hoc analysis of data from the TEMPO 3:4 trial, which randomized 1445 patients with autosomal dominant polycystic kidney disease to tolvaptan or placebo. Their analysis shows that directly after start of tolvaptan therapy, BP does not change, but in the long term, BP gradually becomes lower in patients with tolvaptan compared with placebo. This observation might be attributed to the beneficial effect of tolvaptan on disease progression, a sustained natriuretic effect, or both. Background The V2 receptor antagonist tolvaptan is prescribed to patients with autosomal dominant polycystic kidney disease to slow disease progression. Tolvaptan may alter BP via various acute and chronic effects. Methods To investigate the magnitude and time course of the effect of tolvaptan use on BP, we conducted a post hoc study of the TEMPO 3:4 trial, which included 1445 patients with autosomal dominant polycystic kidney disease randomized 2:1 to tolvaptan or placebo for 3 years. We evaluated systolic and diastolic BP, mean arterial pressure, hypertension status, and use and dosing of antihypertensive drugs over the course of the trial. Results At baseline, BP did not differ between study arms. After 3 weeks of tolvaptan use, mean body weight had decreased from 79.7 to 78.8 kg, and mean plasma sodium increased from 140.4 to 142.6 mmol/L (both P <0.001), suggesting a decrease in circulating volume. We observed none of these changes in the placebo arm. Nonetheless, BP remained similar in the study arms. After 3 years of treatment, however, mean systolic BP was significantly lower in participants receiving tolvaptan versus placebo (126 versus 129 mm Hg, respectively; P =0.002), as was mean diastolic BP (81.2 versus 82.6 mm Hg, respectively; P =0.01). These differences leveled off at follow-up 3 weeks after discontinuation of the study medication. Use of antihypertensive drugs remained similar in both study arms during the entire study. Conclusions Long-term treatment with tolvaptan gradually lowered BP compared with placebo, which may be attributed to a beneficial effect on disease progression, a continued natriuretic effect, or both. Clinical Trial registry name and registration number: TEMPO 3:4, NCT00428948
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Fielding , Henkel, Vanessa, Herb, Marc , Herman-Antosiewicz, Anna , Hernández, Agustín , Hernández, Carlos , Hernández-Díaz, Sergio , Hernández–Gea, Virginia , Herpin, Amaury , Herreros, Judit , Hervás, Javier H. , Hesselson, Daniel , Hetz, Claudio , Higuchi, Yujiro , Hilfiker, Sabine , Hill, Joseph A., Ho, Emmanuel A. , Ho, Idy H. T. , Ho, Philip Wing‐Lok , Ho, Shu‐Leong , Ho, Wan Yun, Hoet, Peter , Hofius, Daniel , Höhn, Annika , Hong, Yi-Ren Hong Chang-Won, Hooper, Lora V. , Hsin, I‐Lun , Hu, Bing , Hu, Dong , Hu, Wei , Hu, Zhuowei , Hua, Jinlian, Huan, Chongmin , Huang, Chuanshu , Huang, Chunling , Huang, Haishan , Huang, Michael , Huang, Shan , Huang, Tianzhi , Huang, Xing , Huang, Yuxiang , Hubert, Virginie , Hübner, Christian A. , Hughes, Stephanie M. , Hughes, William E. , Hummer, Gerhard , Hurley, James H. , Hussain, Sabah N. A. , Hussain, Salik , Hutabarat, Martina , Hwang, Hui-Yun, Ieni, Antonio , Ikeda, Fumiyo , Imagawa, Yusuke , Imbriano, Carol , Imoto, Masaya , Inman, Denise M. , Inoki, Ken , Iozzo, Renato V. , Iribarren, Pablo , Ishaq, Mohd , Ishimwe, Nestor , Ismail, Nahed , Issazadeh‐Navikas, Shohreh , Itakura, Eisuke , Ito, Daisuke , Ivankovic, Davor , Ivanova, Saška , Iyer, Anand Krishnan V. , Izquierdo, José M. , Jacobo‐Herrera, Nadia , Jacquin, Élise , Jadiya, Pooja , Jaeschke, Hartmut , Jagannath, Chinnaswamy, Jakobsson, Johan , Janji, Bassam , Jansen‐Dürr, Pidder , Jansson, Patric J. , Januszewski, Sławomir, Jeltsch‐David, Hélène , Jenny, Andreas , Jensen, Thomas E. , Jessen, Niels , Jia, Lijun , Jia, Rui , Jiang, Qing , Jiang, Richeng , Jiang, Teng , Jiang, Xuejun , Jiang, Yu , Jiménez-Sánchez, María , Jin, Fengyan , Jin, Li , Jin, Luqi, Jin, Si , Joffre, Carine , Johnston, Simon A. , Jokitalo, Eija , Juárez, Esmeralda , Juhász, Gábor , Jun, Youngsoo , Jung, Chang Hwa , Jung, Sung‐Chul , Jungbluth, Heinz , Jungverdorben, Johannes , Just, Steffen , Kaasik, Allen , Kaganovich, Daniel , Kain, Renate , Kajimura, Shingo , Kalamvoki, Maria , Kalia, Manjula , Kalinowski, Danuta S. , Kaludercic, Nina , Kalvari, Ioanna , Kamińska, Joanna , Kanamori, Hiromitsu , Kang, Chanhee , Kang, Rui , Kang, Sang Sun , Kaniyappan, Senthilvelrajan , Kanki, Tomotake , Kanneganti, Thirumala‐Devi , Kanthasamy, Arthi , Kantorow, Marc , Kapuy, Orsolya , Karim, Md. Razaul , Kato, Masaru , Kauppinen, Anu , Kaushal, Gur P. , Kawasaki, Kiyoshi, Kazan, Kemal , Keber, Ursula , Keller, Kate E. , Kenific, Candia M. , Kepp, Oliver , Kern, Andreas , Keulers, Tom G. , Khalfin, Boris , Khalil, Hany , Khan, Shahid Y. , Khandelwal, Vinoth Kumar Megraj, Khandia, Rekha , Kho, Widuri , Khobrekar, Noopur V. , Khuansuwan, Sataree , Khundadze, Mukhran , Killackey, Samuel A. , Kim, Dasol , Kim, Deok Ryong, Kim, Do‐Hyung , Kim, Dong‐Eun , Kim, Eun‐Kyoung , Kim, Hak-Rim, Kim, Hee-Sik , Kim, Hyung-Ryong, Kim, Jeong Hun , Kim, Joungmok , Kim, Seong‐Jun , Kimball, Scot R., Kimchi, Adi , Kimmelman, Alec , Kimura, Tomonori , King, Matthew, Kinsey, Conan G. , Kirshenbaum, Lorrie A. , Kishi, Shuji , Kitamoto, Katsuhiko , Kitaoka, Yasushi , Kitazato, Kaio, Kitsis, Richard N. , Kjærulff, Ole , Klein, Peter S. , Klopstock, Thomas , Klucken, Jochen , Knævelsrud, Helene , Ko, Fred , Kobayashi, Satoru, Koch, Ina , Koch, Jan Christoph , Kögel, Donat , Koh, Young Ho , Kocatürk, Nur Mehpare , Komatsu, Masaaki, König, Jeannette , Kono, Toru, Korkmaz, Gözde , Korsnes, Mónica Suárez , Koskela, Ali , Kota, Janaiah , Kotake, Yaichiro , Kotler, Monica L., Kou, Yanjun , Koukourakis, Michael I., Koustas, Evangelos , Kovács, Tibor , Kovács, Tibor, Kraft, Claudine , Krainc, Dimitri, Krämer, Helmut, Krasnodembskaya, Anna , Kretz‐Remy, Carole , Kroemer, Guido, Kuenen, Sabine , Kuerschner, Lars , Kukar, Thomas , Kumar, Ajay , Kumar, Deepak, Kumar, Dhiraj, Kumar, Sharad , Kume, Shinji , Kumsta, Caroline , Kundu, Chanakya Nath , Kundu, Mondira, Kunnumakkara, Ajaikumar B. , Kutlu, Özlem , Kwak, SeongAe , Kwon, Yong Tae , Spada, Albert La, Labonté, Patrick , Ladoire, Sylvain , Laface, Ilaria, Lafont, Frank , Lagace, Diane C. , Lahiri, Vikramjit , Lai, Zhibing, Laird, Angela S. , Lakkaraju, Aparna , Lan, Sheng‐Hui , Landajuela, Ane , Lane, Darius J.R. , Lange, Carsten , Langer, Rupert , Lapaquette, Pierre, Laporte, Jocelyn , Lastres-Becker, Isabel, Lau, Wilson Chun Yu , Laurie, Gordon W. , Le, Weidong, Stunff, Hervé Le , Leary, Alexandre Y , Lebrun, Jean-Jacques, Leck, Lionel , Lee, Changwook , Lee, Chung‐Pei , Lee, Da-Hye , Lee, Edward B., Lee, Erinna F. , Lee, Gyun Min, Lee, He-Jin, Lee, Heung Kyu , Lee, Jason S. , Lee, Jin-A, Lee, Joo‐Yong , Lee, Michael , Lee, Min Goo , Lee, Min Jae, Lee, Myung‐Shik , Lee, Sangyoon , Lee, Stella Y. , Lee, Sung, Lee, Won Hee , Lee, Yong‐ho , Lee, Youngil , Lei, Yu L., Lei, Yuchen , Leikin, Sergey , Lemus, Leticia , Leng, Shuilong, Lenoir, Olivia , Lenz, Guido , Lenz, Heinz Josef, Lenzi, Paola, León, Yolanda , Leschczyk, Christoph, Leskelä, Stina, Letellier, Elisabeth , Leung, Chi-Ting, Leung, Po Sing , Leventhal, Jeremy S. , Levine, Beth, Lewis, Patrick A. , Ley, Klaus , Li, Bin , Li, Da‐Qiang , Li, Jian‐Ming , Li, Jiong , Li, Liwu , Li, Mei , Li, Ming , Li, Mingchuan , Li, Pin‐Lan, Li, Ming‐Qing , Li, Qing , Li, Sheng , Li, Wei , Li, Wenming , Li, Xue , Li, Yi-Ping, Li, Yuan , Li, Zhiqiang, Li, Zhiyong , Li, Zhiyuan , Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liang, Weicheng , Liang, Yongheng, Liang, YongTian , Liao, Guanghong , Liao, Lujian , Liao, Yung-Feng, Librizzi, Mariangela, Lie, Pearl P.Y. , Lim, Hyunjung J., Lima, Thania Rios Rossi , Limana, Federica , Lin, Chao , Lin, Chih-Wen, Lin, Dar‐Shong , Lin, Fu‐Cheng , Lin, Jiandie D. , Lin, Kurt M., Lin, Kwang‐Huei , Lin, Qiong, Lin, Shaofeng , Lin, Su-Ju, Lin, Wenyu , Lin, Yao‐Xin , Lin, Yee‐Shin, Linden, Rafael, Lindner, Paula , Lipinski, Marta M. , Lipovšek, Saška, Lisiak, Natalia , Liton, Paloma B. , Liu, Chao , Liu, Ching‐Hsuan , Liu, Fang , Liu, Hua-feng , Liu, Huifang , Liu, Jia , Liu, Jing , Liu, Leyuan, Liu, Wei , Liu, Wende , Liu, Xiao-Hong, Liu, Xu , Liu, Yanfen , Liu, Yang, Liu, Yang, Liu, Yueyang , Liu, Yule , Livingston, J. 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H. , Ma, Ning-Fang, Ma, Quanhong , Ma, Xinliang , Ma, Yueyun , Ma, Zhenyi , MacDougald, Ormond A. , MacIntosh, Gustavo C. , Macleod, Kay F. , Maday, Sandra , Madeo, Frank , Madesh, Muniswamy , Madl, Tobias , Madrigal‐Matute, Julio , Maeda, Akiko, Maejima, Yasuhiro , Magariños, Marta , Mahavadi, Poornima , Maiani, Emiliano , Maiese, Kenneth , Maiti, Panchanan , Maiuri, Maria Chiara , Major, Michael Ben, Makareeva, Elena , Malik, Fayaz , Mallilankaraman, Karthik , Maloyan, Alina , Mammadova, Najiba, Man, Gene Chi Wai , Manai, Federico , Mancias, Joseph D. , Mandelkow, Eva‐Maria , Manfredi, Angelo A. , Manshian, Bella B. , Manzano, Raquel , Marchese, Chiara , Marchetti, Sandrine , Marcucci, F, Mardente, Stefania , Mareninova, Olga A. , Mari, Muriel , Marinelli, Sara , Mariño, Guillermo , Mariotto, Sofia , Martin, Alexandre , Martin, Katie R. , Martin, Sara L. , Martín‐Segura, Adrián , Martin-Burriel, Inmaculada, Martín-Rincón, Marcos , Martín‐Sanz, Paloma , Martinez, Aitor , Martı́nez, Ana , Martinez-Lopez, Nuria, Martínez‐Vicente, Marta , Martins, Daniel Oliveira , Martins, Joilson O. , Martins, Waleska K. , Martins-Marques, Tania, Marzetti, Emanuele , Masaldan, Shashank , Masclaux-Daubresse, Celine, Mashek, Douglas G. , Massa, Valentina , Massieu, Lourdes , Masyuk, Anatoliy I. , Masyuk, Tetyana V., Matheu, Ander , Matoba, Satoaki , Matsuzaki, Sachiko , Mattar, Pamela , Mattè, Alessandro , Mauriz, José L., Mauthe, Mario , Maycotte, Paola , Mayer, Johanna , Mazzoni, Cristina , Mazzulli, Joseph R. , McCarty, Nami , McGill, Mitchell R. , McKenna, Sharon L. , McLoughlin, Fionn , McNiven, Mark A., McWilliams, Thomas G. , Medeiros, Tania , Medina, Diego L., Megeney, Lynn A. , Megyeri, Klára , Mehrpour, Maryam , Mehta, Jawahar L. , Meijer, Alfred J., Mejlvang, Jakob , Meléndez, Alicia , Melk, Annette, Memişoğlu, Gönen , Mendes, A.F. , Meng, Delong , Meng, Fei, Mercier, A., Mergny, Jean‐Louis , Merkley, Seth D. , Meske, Volker, Mestre, Ana Cecilia, Metur, Shree Padma, Meyer, C., Meyer, Hemmo , Mi, Wenyi , Mialet‐Perez, Jeanne , Miao, Jun‐Ying, Micale, Lucia , Miki, Yasuo, Milan, Enrico , Milczarek, Małgorzata , Miller, Samuel I. , Millward, Steven W. , Mirzaei, Hamed, Mirzaei, Hamid Reza , Mirzaei, Mehdi , Mishra, Amit , Mishra, Nandita , Mishra, Paras Kumar, Misirkić, Maja , Misasi, Roberta, Misra, Amit , Misso, Gabriella , Mitchell, Claire H. , Mitou, Géraldine, Miura, Tetsuji , Miyazaki, Makoto, Miyazaki, Mitsunori , Miyazaki, Taiga , Miyazawa, Keisuke, Mizushima, Noboru , Mogensen, Trine H. , Mohammadinejad, Reza , Mohamud, Yasir , Mohanty, Abhishek , Möhlmann, Torsten , Moley, Kelle H. , Möller, Andreas, Mollereau, Bertrand , Mollinedo, Faustino, Montagna, Costanza , Monteiro, Mervyn J. , Montella, Andrea , Montes, L. Ruth , Montico, Barbara , Mony, Vinod K., Compagnoni, Giacomo Monzio , Moore, Michael N. , Moosavi, Mohammad Amin , Morales‐Álamo, David , Moratalla, Rosario , Moreira, Paula I. , Morelli, Elena , Moreno-Blas, Daniel , Morgan, Alwena H. , Morin, Fabrice , Morishita, Hideaki , Moriyama, Mariko , Moriyasu, Yuji, Morleo, Manuela , Morselli, Eugenia , Moruno-Manchon, Jose F. , Moscat, Jorge , Motori, Elisa , Moura, Andréa Felinto , Mrakovcic, Maria, Muciño-Hernández, Gabriel, Mukherjee, Anupam , Mukhopadhyay, Subhadip , Levy, Jean M. 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Celeste, Nicoli, Francesco , Nieto‐Díaz, Manuel , Niranjan, Rituraj , Nishimune, Hiroshi , Niso-Santano, Mireia, Nixon, Ralph A. , Nobili, Annalisa , Noda, Takeshi , Nogueira-Recalde, Uxía , Nombela, Iván , Novak, Ivana, Novoa, Beatriz , Nukina, Nobuyuki , Nussbaum-Krammer, Carmen, Nylandsted, Jesper , O’Donovan, Tracey R. , O’Leary, Seónadh M. , O’Rourke, Eyleen J. , O’Sullivan, Mary P. , O’Sullivan, Timothy E., Oddo, Salvatore , Oehme, Ina, Ogawa, Michinaga , Ogier‐Denis, Éric , Ögmundsdóttir, Margrét H. , Öğretmen, Besim , Oh, Goo Taeg , Oh, Seon‐Hee , Oh, Young J. , Ohama, Takashi, Ohashi, Yohei , Ohmuraya, Masaki, Oikonomou, Vasileios , Ojha, Rani , Okazawa, Hitoshi , Oku, M., Oliván, Sara , Oliveira, Jorge M.A. , Ollmann, Michael, Olzmann, James A. , Omari, Shakib , Önal, Gizem, Ondrej, Martin , Ong, Sang‐Bing , Onnis, Anna , Orellana, Juan , Orellana‐Muñoz, Sara , Ortega-Villaizán, María del Mar , Ortiz‐González, Xilma R. , Osiewacz, Heinz D. , Osman, Abdel‐Hamid K. , Otsu, Kinya, Ott, Christiane , Ou, Jing-hsiung James, Outeiro, Tiago F., Öztürk, Melek , Pagès, Gilles, Pahari, Susanta , Pajares, Marta, Pal, Rituraj, Paladino, Simona , Palmieri, Michela , Palmisano, Giuseppe , Pan, Qingjun , Pan, Xin , Panasyuk, Ganna , Pandey, Rahul , Pandey, Udai B., Pandya, Vrajesh , Paneni, Francesco , Pang, Shirley Yin-Yu, Papademetrio, Daniela L. , Papinski, Daniel, Papp, Diana , Park, Hwan Tae , Park, Ji-Man, Park, Jong‐In , Park, Junsoo, Park, Sang-Youel, Pasquier, Adrien , Pasquier, Benoit , Passos, João F. , Pastore, Nunzia , Patschan, Daniel , Pattingre, Sophie , Pedraza‐Alva, Gustavo , Pedraza-Chaverri, Jose, Pedrozo, Zully , Pei, Gang , Pei, Jianming , Peled-Zehavi, Hadas, Pellegrini, Joaquín Miguel , Pelletier, Joffrey , Peñalva, Miguel A., Peng, Di , Peng, Ying , Pennuto, Maria , Pentimalli, Francesca , Pereira, Cláudia MF, Pereira, Gustavo J.S. , Pereira, Lílian Cristina , Almeida, Luís Pereira de , Perera, Nirma D. , Pérez-Lara, Ángel, Pérez‐Oliva, Ana B. , Perl, András , Pestell, Richard G. , Petrache, I., Petrovski, Goran , Pfirrmann, Thorsten , Pfister, Astrid S., Pi, Huifeng , Pickrell, Alicia M. , Picot, Sandy, Pierantoni, Giovanna Maria , Pierre, Philippe , Pierrefite‐Carle, Valérie , Pierzynowska, Karolina , Pietruczuk, Mirosława , Pimentel-Muiños, Felipe X., Pinar, Mario , Pinheiro, Roberta Olmo , Pinkas‐Kramarski, Ronit , Pircs, Karolina , Piya, Sujan , Pizzo, Paola , Platta, Harald W. , Plomann, Markus , Pocock, Roger , Pöggeler, Stefanie , Pohl, Christian, Poirot, Marc , Poletti, Angelo , Ponpuak, Marisa , Popelka, Hana , Popova, Bilyana , Porta, Helena, Alcón, Soledad Porte , Portilla-Fernández, Eliana , Potts, Malia B. , Powers, Ted, Prahlad, Veena , Prajsnar, Tomasz K. , Praticò, Domenico , Prencipe, Rosaria, Priault, Muriel , Proikas‐Cezanne, Tassula , Puertollano, Rosa , Puglielli, Luigi, Pulinilkunnil, Thomas , Puri, Deepika , Puri, Rajat, Puyal, Julien , Qi, Yongmei , Quadrilatero, Joe , Quarleri, Jorge, Raben, Nina, Rabinowich, Hannah, Ragona, Debora, Rahmati, Marveh , Raia, Valeria, Raimundo, Nuno , Rajasekaran, Namakkal-Soorappan, Rao, Sriganesh Ramachandra , Rami, Abdelhaq, Ramírez‐Pardo, Ignacio , Ramsden, D. , Randow, Felix , Ranieri, Danilo , Rao, Hai , Rao, Rekha , Rathore, Sumit , Ratnayaka, J. 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M. , Soldati, Thierry , Soler, Rosa M. , Somarelli, Jason A. , Sonawane, Avinash , Song, Fuyong, Song, Hyun Kyu , Song, Kunhua , Sorice, Maurizio , Soukas, Alexander A. , Soukup, Sandra‐Fausia , Sousa, Diana , Sousa, Nadia, Bharath, M. M. Srinivas , Clair, Daret St., Stagni, Venturina, Staiano, Leopoldo , Stankov, Metodi V. , Stathopulos, Peter B. , Stefan, Katja, Stefan, Sven Marcel , Stefanis, Leonidas, Steffan, Joan S. , Steinkasserer, Alexander , Stenmark, Harald, Sterneckert, Jared , Stevens, Craig , Storch, Stephan , Strappazzon, Flavie , Strohecker, Anne M. , Stupack, Dwayne G., Su, Huanxing , Su, Ling‐Yan , Suarez-Fontes, Ana Márcia , Subirada, Paula V., Sudhandiran, Ganapasam, Sue, Carolyn M. , Sui, Xinbing , Summers, Corey M., Sun, Guangchao , Sun, Zhongjie , Sunahara, Karen K. S. , Susztak, Katalin, Šutovský, Peter , Suzuki, Hidekazu , Sweeney, Gary , Symons, J. David , Sze, Stephen Cho Wing , Szewczyk, Nathaniel J. , Tabęcka-Łonczynska, Anna, Tabolacci, Claudio , Taegtmeyer, Heinrich, Tagaya, Mitsuo , Tai, Haoran , Tait, Stephen W. G., Takahashi, Yoshinori , Tam, Chit , Tam, Shing Yau , Tampellini, Davide , Tamura, Atsushi , Tan, Eng-King, Tan, Ya‐Qin , Tanaka, Masaki , Tang, Daolin , Tang, Jingfeng , Tang, Tie-Shan , Tao, Zhipeng , Taouis, Mohammed , Tavernarakis, Nektarios, Taylor, Allen, Teixeira, Natércia , Tekirdağ, Kumsal Ayşe, Tencomnao, Tewin , Tenreiro, Sandra , Tharaux, Pierre‐Louis , Thedieck, Kathrin , Thekkinghat, Arvind A. , Thinwa, Josephine , Thirumalaikumar, Venkatesh P. , Thomes, Paul G. , Thorburn, Andrew , Thum, Thomas, Thumm, Michael , Tian, Ling, Tichý, Aleš , Timmerman, Vincent , Titorenko, Vladimir I. , Toivonen, Janne M. , Tomaipitinca, Luana , Tomar, Dhanendra , Tomás‐Zapico, Cristina , Tomić, Sergej , Tong, Chao, Tong, Xin , Torgersen, Maria L., Torii, Satoru , Torres-López, Liliana , Torriglia, Alicia , Towers, Christina G. , Towns, Roberto, Tran, Quynh‐Giao , Travassos, Leonardo H. , Tremel, Shirley , Trougakos, Ioannis P., Tsao, Betty P. , Tse, Tak Fu, Tsvetkov, Andrey S. , Tumbarello, David A. , Tyler, Jessica K., Tyutereva, Elena V. , Uchiyama, Yasuo , Ugun‐Klusek, Aslihan , Uhlig, Holm H. , Ułamek-Kozioł, Marzena, Ulasov, Ilya V. , Umekawa, Midori, Ungermann, Christian , Urbe, Sylvie, Uribe-Carretero, Elisabet , Uversky, Vladimir N. , Vaccaro, María I. , Vahsen, Björn F. , Vakifahmetoglu-Norberg, Helin, Valdor, Rut , Valente, Maria João , Valko, Ayelén , Vallée, Richard, Valverde, Ángela M. , Berghe, Greet Van den, Veen, Stijn van der , Kaer, Luc Van , Loosdregt, Jorg van , Wijk, Sjoerd J. L. van , Vandenberghe, Wim , Vanhorebeek, Ilse , Vannier-Santos, Marcos A., Vannini, Nicola , Vanrell, M. Cristina, Vantaggiato, Chiara , Varela‐Nieto, Isabel , Varga, Máté , Vasconcelos, M. Helena , Vats, Somya , Vega-Rubín-de-Celis, Silvia , Velasco, Guillermo , Velázquez, Ariadna P., Vellai, Tibor , Vellenga, Edo , Verdier, Mireille , Verginis, Panayotis , Vergne, Isabelle , Verkade, Paul , Verma, Manish , Verstreken, Patrik , Vervliet, Tim , Vervoorts, Jörg , Víctor, Víctor M., Vidoni, Chiara , Vieira, Otília V. , Vierstra, Richard D., Viganò, Sonia , Vihinen, Helena , Vijayan, Vinoy, Vila, Miquel , Villalba, José M., Villalobo, Antonio , Villarejo‐Zori, Beatriz , Vincent, Olivier , Vindis, Cécile , Viret, Christophe , Vocadlo, David J. , Voitsekhovskaja, Olga V. , Volonté, Cinzia , Volta, Mattia , Vomero, Marta , Haefen, Clarissa von, Vooijs, Marc , Voos, Wolfgang , Vučićević, Ljubica , Waguri, Satoshi , Waite, Kenrick A., Wakatsuki, Shuji , Walker, David W., Walker, Mark J. , Walter, Jochen, Wandosell, Francisco , Wang, Bo , Wang, Chao-Yung, Wang, Chen , Wang, Chenran, Wang, Chenwei , Wang, Cun-Yu, Wang, Fengming, Wang, Han, Wang, Hexiang , Wang, Hong‐Gang , Wang, Jianrong, Wang, Jigang , Wang, Jun-Dong , Wang, Kui , Wang, Lianrong, Wang, Liming , Wang, Maggie Haitian, Wang, Meiqing , Wang, Nanbu , Wang, Pengwei , Wang, Ping , Wang, Ping, Wang, Q., Wang, Qiong , Wang, Wentao , Wang, Xinnan, Wang, Xuejun , Wang, Yan, Wang, Yanchang , Wang, Yanzhuang , Wang, Yihua , Wang, Yu , Wang, Yuqi , Wang, Zhe, Wang, Zhenyu , Wang, Zhouguang , Watanabe, Eizo, Watchon, Maxinne , Wawrzyńska, Anna , Weaver, Timothy E., Węgrzyn, Grzegorz, Wehman, Ann M. , Wei, Huafeng , Wei, Taotao , Wei, Yongjie, Weiergräber, Oliver H. , Weihl, Conrad C., Weindl, Günther , Weiskirchen, Ralf , Wen, Runxia H. , Werner, Antonia, Weykopf, Beatrice , Whitton, J. Lindsay , Wiktorska, Katarzyna , Wildenberg, Manon E. , Wileman, Tom, Wilkinson, Simon , Williams, Brett, Williams, Robin S. B. , Williamson, Peter R. , Wilson, Richard A. , Winsor, Nathaniel J. , Wodrich, Harald , Woehlbier, Ute , Wollert, Thomas , Wong, Richard W., Wong, Vincent Kam Wai , Wong, W. Wei-Lynn, Wu, Anguo , Wu, Kenneth K., Wu, Shan‐Ying , Wu, William Ka Kei , Wu, Shufang, Wu, Xiaoqing , Wu, Yao‐Wen , Wu, Yihua , Xavier, Ramnik J. , Xia, Hongguang , Xia, Lixin , Xia, Zhengyuan , Ge, Xiang , Xiang, Jin , Xiang, Mingliang , Xiang, Wei , Xiao, Guozhi , Xiao, Hengyi , Xiao, Hongtao , Xiao, Jian, Xiao, Lan , Xiao, Shi , Xiao, Yin , Xie, Baoming, Xie, Zhiping , Xie, Min , Xie, Yuxiang , Xie, Zhonglin, Xilouri, Maria , Xu, En , Xu, Jin‐Rong , Xu, Liang , Xu, Xiulong , Xue, Yu , Yakhine-Diop, Sokhna M. S. , Yamaguchi, Masamitsu , Yamamoto, Ai , Yamashina, Shunhei, Yan, Shengmin , Yan, Shian-Jang, Yan, Zhen , Yang, Chuanbin , Yang, Dun-Sheng, Yang, Huan , Yang, Huang-Tian, Yang, Hui , Yang, Jing , Yang, Jingyu , Yang, Ling , Liu, Yang , Yang, Ming , Yang, Seungwon, Yang, Shu , Yang, Shun-Fa , Yang, Wannian, Yang, Wei , Yang, Xiaoyong , Yang, Yi , Yao, Xiaoqiang , Yao, Yong-Gang , Yao, Yong-ming, Yasui, Takahiro , Yazdankhah, Meysam, Yi, Cong , Yin, Xiao-Ming , Yin, Yanhai , Yin, Zhangyuan , Yin, Ziyi , Ying, Meidan , Ying, Zheng, Yip, Calvin K. , Yiu, Stephanie Pei Tung , Yoo, Young Hyun , Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan , Yu, Haiyang , Yu, Jun, Li, Yu , Yu, Ming‐Lung , Yu, Seong-Woon, Yu, Victor C. , Yu, Zhengping, Yuan, Junying , Yuan, Ling‐Qing , Yuan, Shilin , Yuan, Yanggang , Yuan, Zengqiang , Yue, Jianbo , Yue, Zhenyu , Yung, Raymond , Zacks, David, Zaffagnini, Gabriele , Zambelli, Vanessa O. , Zanella, Isabella , Zang, Qun S. , Zanivan, Sara , Zappavigna, Silvia , Zaragoza, P. , Zarbalis, Konstantinos S., Zarebkohan, Amir , Zarrouk, Amira , Zeitlin, Scott, Zeng, Jialiu , Zeng, Judeng , Žerovnik, Eva , Zhan, Lixuan , Zhang, Donna D., Zhang, Hong , Zhang, Honghe , Zhang, Huafeng , Zhang, Huaye, Zhang, Huiling , Zhang, Jianbin , Zhang, Jingpu , Zhang, Kalin Yanbo , Zhang, Leshuai W. , Zhang, Lu , Zhang, Luoying , Zhang, Menghuan, Zhang, Peng , Zhang, Sheng , Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei , Zhang, Xiaoyan , Zhang, Xin , Zhang, Xinxin , Zhang, Yang, Zhang, Yi , Zhang, Yingdong , Zhang, Yuanyuan , Zhang, Yuchen , Zhang, Zhe , Zhang, Zhibing , Zhang, Zili , Zhao, Haobin, Zhao, Lei , Zhao, Shuang , Zhao, Tongbiao , Zhao, Ying, Zhao, Yongchao , Zhao, Yongliang , Zhao, Yuting , Zheng, Guoping , Zheng, Kai, Zheng, Ling , Zheng, Shizhong , Zheng, Xi‐Long , Zheng, Zu‐Guo , Zhivotovsky, Boris, Zhong, Qing , Zhou, Ao, Zhou, Ben , Zhou, Cefan , Zhou, Gang , Zhou, Hongbo , Zhou, Kailiang, Zhou, Rongjia , Zhou, Yanshuang, Zhou, Yinghong , Zhou, Yubin , Zhou, Zhengyu, Zhou, Zhou , Zhu, Binglin , Zhu, Changlian , Zhu, Guo‐Qing , Zhu, Haining , Zhu, Hongxin, Zhu, Yanping , Zhu, Yushan , Zhuang, Haixia , Zhuang, Xiaohong , Zimmermann, Christine , Żołądek, Teresa , Zong, Wei‐Xing, Zorov, Dmitry B. , Zorzano, Antonio, Zou, Weiping, Zou, Zhen , Zou, Zhengzhi, Zuryn, Steven , Kenchappa, Chandra Shekar, Li, Zuguo , Lin, Yong , Sluimer, Judith C. , Stallings, Christina L. , Tong, Chun-Kit, Wang, Ping , Hu, Bo , Lee, Edward B. , Tse, Hung‐Fat , Suszták, Katalin , Lei, Yu Leo , Yu, M-L , Dai, Yun , Bartolome, Alberto , Brown, Rhoderick E , Passos, João F , Paneni, Francesco , Sahin, Özgür , Pereira de Almeida, Luis , Ren, Jun , Bornhauser, Beat , Kumar, Sharad , Sampaio-Marques, Belém , Ludovico, Paula , Luftig, Micah , Begun, Jakob , Krasnodembskaya, Anna D , Dafsari, Hormos Salimi , Chevet, Eric , Tse, Hung-Fat , Barmada, Sami , Ebrahimi-Fakhari, Darius , Cavadas, Claudia , Sue, Carolyn M , Cardenal-Muñoz, Elena , Lee, Edward B , Golebiewska, Anna , Calbet, Jose A L , Boya, Patricia , Maday, Sandra , Klionsky, Daniel J. , Abdelfatah, Sara , Abdoli, Asghar , Agarwal, Anupam , Ahmed, Zubair M. , Alcocer‐Gómez, Elísabet , Ali, Muhammad , Al‐Bari, Md. Abdul Alim , Aliwaini, Saeb H. , Alizadeh, Javad , Almacellas, Eugènia , Almasan, Alexandru , Alonso, G. , Altieri, Dario C. , Andersen, Stig Uggerhøj , Andrade-Silva, Magaiver , Angelini, Sabrina , Apostolova, Nadezda , Arasaki, Kohei , Araújo, Wagner L. , Arden, Catherine , Arimoto, Hirokazu , Armstrong-James, Darius P. H. , Pelloquin, Laetitia , Aschner, Michael , Ashrafizadeh, Milad , Autelli, Riccardo , Aveic, Sanja , Avin‐Wittenberg, Tamar , Ayton, Scott , Backues, Steven K. , Bae, Dong-Hun , Bae, Ok‐Nam , Baek, Ahruem , Baek, Seung‐Hoon , Baek, Sung Hee , Bai, Jie , Bai, Yidong , Baldari, Cosima T. , Balduini, Walter , Ballabio, Andrea , Banerjee, Sreeparna , Bao, Yan , Baptista, Maurı́cio S. , Barreto, George Emilio , Basagoudanavar, Suresh H. , Bast, Robert C. , Basu, Alakananda , Batoko, Henri , Batten, Isabella , Behrens, Georg M. N. , Bei, Roberto , Behl, Christian , Bello‐Morales, Raquel , Beltrán, Sebastián , Bergami, Matteo , Bergmann, Andreas , Berthoux, Lionel , Bhattacharya, Resham , Bhattacharyya, Shalmoli , Bhutia, Sujit Kumar , Bi, Lanrong , Birgisdottir, Åsa Birna , Bjørkøy, Geir , Blomgren, Klas , Boada-Romero, Emilio , Boesze‐Battaglia, Kathleen , Bonifacino, Juan S. , Boone, Brian A. , Borthakur, Gautam , Bosch, Jürgen , Bose, Santanu , Botana, Luis Miguel , Boulton, Michael E. , Bourdenx, Mathieu , Brackney, Doug E. , Brandts, Christian , Braun, Ralf J. , Braus, Gerhard H. , Bravo, Roberto , Brody, Steven L. , Brown, Carolyn Nicole , Brumell, John Hunter , Brunetti‐Pierri, Nicola , Buitrago‐Molina, Laura Elisa , Buraschi, Simone , Buch, Shilpa J. , Butturini, Elena , Cairó, Montserrat , Caldwell, Kim A. , Campbell‐Valois, François‐Xavier , Campello, Silvia , Campesi, Ilaria , Almeida, Danilo Cândido de , Canesi, Laura , Caraglia, Michele , Carchman, Evie H. , Carmona‐Gutiérrez, Didac , Carnevali, Oliana , Carrier, Lucie , Carroll, Bernadette , Carter, A. Brent , Casas, Caty , Castillo, Eliseo F. , Castro‐Caldas, Margarida , Castro‐Obregón, Susana , Catz, Sergio , Cayuela, María Luisa , Cecarini, Valentina , Cecconi, Francesco , Cenci, Simone , Ceperuelo‐Mallafré, Victòria , Cervia, Davide , Chae, Han–Jung , Chakrabarti, Oishee , Chan, Edmond Y. W., Chan, Edward D. , Chandra, Partha Kumar , Chang, Chih‐Peng , Chang, Chunmei , Chapman, Tracey , Chen, Guang‐Chao , Chen, Leilei , Chen, Lin , Chen, Quan , Chen, Ruey‐Hwa , Chen, Shi , Chen, Wei‐Qiang , Chen, Xu , Chen, Yu-Jen , Chen, Yujie , Chen, Zhi , Chen, Zhijian J. , Chen, Zhixiang , Cheng, Hanhua , Cheng, Jun , Cheng, Shi‐Yuan , Cheng, Wei Nee , Cheng, Xiaodong , Chen, Zhong , Cheong, Heesun , Chernyak, Boris V. , Chi, Richard J., Chiang, Aks , Chiarelli, Roberto , Chu, Charleen T. , Chung, Seockhoon , Cianfanelli, Valentina , Cifuentes, Mariana , Cirone, Mara , Clague, Michael J. , Cohen, Ehud , Cohen, Mickaël M. , Čolić, Miodrag J , Combaret, Lydie , Comincini, Sergio , Conte, Andrea, Conti, Fabrizio , Coppens, Isabelle , Corasaniti, Maria Tiziana , Corkery, Dale , Cordes, Nils , Cortese, Katia , Coto‐Montes, Ana M. , Crack, Peter John , Crespo, José L. , Cuadrado, Antonio , Cui, Jun , Cui, Yong , D’Arcangelo, Daniela , D’Lugos, Andrew C. , Dagda, Ruben Karim , Dagdas, Yasin , Daμμe, Markus , Dantuma, Nico P. , Darling, April L. , Dasarathy, Srinivasan , Daumke, Oliver , Davis, Tanja , Amicis, Francesca De , Felice, Francesca De , Franceschi, Lucia De , Milito, Angelo De , Nunzio, Cosimo De , Santi, Mauro De , Debnath, Jayanta , DeBosch, Brian J. , DeGregori, James V. , Rio, Gabriel del , Delbridge, Lea M.D. , Delpino, M. Victoria , Demarchi, Francesca , Dembitz, Vilma , Deng, Zhiqiang , Denton, Donna , Der, Channing J , Deretić, Vojo , Dhiman, Rohan , Bernardo, Diego di , Cristina, Manlio Di , Nardo, Alessia Di, Sano, Federica Di , Diallinas, George , Diaz-Araya, Guillermo, Đikić, Ivan , Ding, Wen‐Xing , Dini, Luciana , Dionne, Marc , Diwan, Abhinav , Dixon, Ian , Djavaheri‐Mergny, Mojgan , Dobrinski, Ina , Dobrovinskaya, Oxana R. , Dobrowolski, Radek , Dobson, Renwick C. J. , Donadelli, Massimo , Dong, Bo, Dötsch, Volker , Dou, Huan , Dridi, Sami , Du, Caigan , Du, Li‐Lin , Dubrovska, Anna , Dunlop, Elaine A. , Dwarakanath, Bilikere Srinivasa Rao , Eftekharpour, Eftekhar , Eichinger, Ludwig , Eissa, N. Tony , Eissa, Sanaa , El‐Naggar, Shahenda , Eliopoulos, Aristides G. , Elks, Philip M. , Emerling, Brooke M. , Engelbrecht, Anna‐Mart , Escobar‐Henriques, Mafalda , Fabriàs, Gemma , Fabrizi, Cinzia , Falkenburger, Björn H. , Fan, Yanbo , Fanto, Manolis , Feng, Du , Feng, Yibin , Feng, Yuchen , Fernández-Checa, José Carlos , Filippi‐Chiela, Eduardo Cremonese , Filomeni, Giuseppe , Fineschi, Vittorio , Flamigni, Flavio , Follo, Carlo , Fon, Edward A , Fornai, Francesco , Fraldi, Alessandro , Franco, Brunella , Franco, Rodrigo , Friedman, Scott L. , Frühbeck, Gema , Fujita, Naonobu , Fujiwara, Yuuki , Fukuda, Mitsunori , Furic, Luc , Fusco, Carmela , Galluzzi, Lorenzo, Gan, Boyi , Gao, Hui , Gao, Shou‐Jiang , Gargini, Ricardo , Garry, Robert F. , Ge, Liang , Ge, Wanzhong , Gelfi, Cecilia , Gentle, Ian Edward , Gewirtz, David A , Ghigo, Alessandra , Giampietri, Claudia , Gibson, Spencer B. , Giniger, Edward , Giorgi, Carlotta , Girão, Henrique , Goldstone, David C. , Gomez‐Puerto, Maria Catalina , Goñi, Félix M. , González‐Hernández, Tomás , Gorbatyuk, Marina S. , Goruppi, Sandro , Gottlieb, Roberta A. , Gozes, Illana , Green, Douglas R. , Grinstaff, Mark W. , Grune, Tilman , Guntur, Anyonya R. , Guo, Lian‐Wang , Gupta, Shashi Kumar , Gustafsson, Åsa B. , Haapasalo, Annakaisa , Hadano, Shinji , Hafrén, Anders , Hall, Belinda S. , Hamann, Andréa , Han, Weidong , Hanson, Phyllis I. , Haroon, Nigil , Harris, James , Hasegawa, Takafumi , Nagoor, Noor Hasima , Hay, Bruce A. , Hayrabedyan, Soren , He, Yu‐Ying , Helgason, G. Vignir , Hergovich, Alexander , Hernández–Gea, Virginia , Heussler, Volker Theo , Hlavacek, William S. , Hobbs, G. Aaron , Hochstrasser, Mark , Hofman, Paul , Holmberg, Carina I. , Hombrebueno, José R. , Hoppe, Thorsten , Horos, Rastislav , Hoshida, Yujin , Hsu, Hsin‐Yun , Hu, Li‐Fang , Hu, Ming Chang , Hu, Ronggui , Hu, Yu‐Chen , Hua, Fang , Hua, Jinlian, Hua, Yingqi , Huang, Canhua , Huang, Chuanxin , Huang, Kun , Huang, Rui , Huber, Tobias Bruno , Humbert, Magali , Hussey, Patrick J. , Hwang, Hui‐Yun , Hwang, Seungmin , Imai, Yuzuru , Iovanna, Juan , Ippolito, Giuseppe , Irazoqui, Javier E. , Ishaq, Mohd, Ishikawa, Makoto , Isidoro, Ciro , Izumi, Masanori , Jäättelä, Marja , Jabir, Majid Sakhi , Jackson, William T. , Jacomin, Anne‐Claire , Jakobi, Arjen J. , Jantsch, Jonathan , Jassey, Alagie , Jean, Steve , Jendelová, Pavla , Jewell, Jenna L. , Ji, Jing , Jiang, Liwen , Jin, Eun‐Jung , Jin, Hongchuan , Jin, Meiyan , Jo, Eun‐Kyeong , Johansen, Terje , Johnson, Gail V.W. , Jolly, Mohit Kumar , Joosten, Leo A. B. , Jordán, Joaquı́n , Joseph, Bertrand , Ju, Dianwen , Ju, Jeong-Sun , Ju, Jingfang , Judith, Delphine , Jung, Yong‐Keun , Kaarniranta, Kai , Kabuta, Tomohiro , Kahana, Alon , Kaminskyy, Vitaliy O. , Kanasaki, Keizo , Kanthasamy, Anumantha G. , Karamouzis, Michalis V. , Karmakar, Parimal , Katare, Rajesh , Kaufmann, Stefan H. E. , Kaushik, Susmita , Kawasaki, Kiyoshi, Ke, Po‐Yuan , Keating, Damien J. , Kehrl, John H. , Keller, Christian W. , Kemper, Jongsook Kim , Kermorgant, Stéphanie , Ketteler, Robin , Khambu, Bilon , Kim, Deok Ryong, Kim, Eun Young , Kim, Jin Kyung , Kim, Jin‐Hoi , Kim, Ju Hwan , Kim, Keun Il , Kim, Peter Kijun , Kinghorn, Kerri J. , Kirkin, Vladimir , Киселев, С. Л. , Kittler, Josef T. , Knorr, Roland L. , Ko, Ben C.B. , Ko, Jiunn‐Liang , Kobayashi, Hotaka , Koenig, Ulrich , Koike, Masato , Kohlwein, Sepp Dieter , Komatsu, Masaaki , Kopp, Benjamin T. , Korcsmaros, Tamas Douglas , Korolchuk, Viktor I. , Kotler, Mónica L. , Koukourakis, Michael Ioannis , Kovács, Tibor, Koya, Daisuke , Kozako, Tomohiro , Krämer, Helmut , Kroemer, Guido , Ktistakis, Nicholas T. , Kuchitsu, Kazuyuki , Kumar, Ashok , Kumar, Deepak, Kundu, Mondira , Kurgan, Lukasz , Kutateladze, Tatiana G. , Kwon, Ho Jeong , Kwon, Taeg Kyu , Kyrmizi, Irene , Spada, Albert R. La , Lai, Zhibing, Lamark, Trond , Lane, Jon D. , Lang, Charles H. , Lange, Carsten, Langel, Ülo , Lapaquette, Pierre , LaRusso, Nicholas F. , Lastres‐Becker, Isabel , Lavandero, Sergio , Law, Hkw , Layfield, Robert , Leduc‐Gaudet, Jean‐Philippe , Lee, He-Jin, Lee, Jae Man , Lee, Jun Hee , Lee, Seung‐Jae , Lee, Ying‐Ray , Lefebvre, Christophe , Legouis, Renaud , Leitinger, Gerd , Lenz, Heinz Josef, León, Yolanda, Leopoldino, Andréia Machado , Leung, Chi-Ting, Levine, Beth , Li, Jing , Li, Ke, Li, Min , Li, Min , Li, Pin‐Lan , Li, Tiangang , Li, Zhiqiang, Lian, Jiqin , Liang, Chengyu, Liang, Qiangrong , Liao, Mingzhi , Lilly, Mary A. , Lin, Liang , Lin, Pei‐Hui , Lin, Xueying , Linden, Rafael , Ling, Shuo‐Chien , Lingor, Paul , Linnemann, Amelia K , Liou, Yih‐Cherng , Lira, Vitor Agnew , Liu, Chunfeng , Liu, Cui Hua , Liu, Hao , Liu, Hsiao‐Sheng , Liu, Julia C. , Liu, Longhua , Liu, Meilian , Liu, Qin , Liu, Xiao-Hong, Liu, Xiaodong , Liu, Xingguo , Liu, Xuedong , Liu, Yang, Liu, Yang, Lizard, Gérard , Llorente, Alicia , Long, Qi , Long, Yun Chau, López, Manuela G. , Lőrincz, Péter , Lovat, Penny E. , Lu, Jin‐Jian , Lum, Julian J., Lünemann, Jan D. , Luo, Shouqing , Ma, Changle , Ma, Mengxiao , Ma, Ning‐Fang , Macián, Fernando , MacKeigan, Jeffrey P. , Majello, Barbara , Malorni, Walter , Mandell, Michael A. , Manjili, Masoud H. , Manjithaya, Ravi R. , Manque, Patrício , Manzoni, Claudia , Mao, Kai, Marconi, Anna Maria , Margeta, Marta , Marinelli, Oliviero , Marshall, Richard Scott , Marten, Mark R. , Martens, Sascha , Martin, Sara, Martín-Acebes, Miguel A. , Martín‐Burriel, Inmaculada , Martina, José A. , Martinet, Wim , Martinez, Jennifer , Martínez‐Velázquez, Moisés , Martinez-Lopez, Nuria, Martins‐Marques, Tânia , Masclaux‐Daubresse, Céline , Masson, Glenn Robert , Masuelli, Laura , Masyuk, Tetyana V., Matarrese, Paola , Mattoscio, Domenico , Mauriz, Jose Luis , Mauvezin, Caroline , Maverakis, Emanual Michael , Mazzoccoli, Gianluigi , McDonald, Christine , McLaughlin, BethAnn , Mechta‐Grigoriou, Fatima , Meijer, Annemarie H. , Meng, Tian, Menna‐Barreto, Rubem F. S. , Menon, Manoj B., Mercer, Carol A. , Mercier, Anne E., Merighi, Adalberto , Merla, Giuseppe , Miller, Dana L. , Miller, Silke , Milošević, Ira , Minina, Elena A. , Mirzaei, Mehdi, Mishra, Paras Kumar , Miyamoto, Shigeki, Miyazawa, Keisuke, Mograbi, Baharia , Mohanty, Abhishek , Mohapatra, Sipra , Mohmmed, Asif , Moles, Anna , Molinari, Maurizio , Mollace, Vincenzo , Møller, Andreas Buch , Mora, Ana Lucia , Mora, Marina, Morelli, Elena, Moreno, Sandra , Moresi, Viviana , Morga, Benjamín , Moritz, Orson L. , Moriyama, Mariko, Mostowy, Serge , Moustaïd‐Moussa, Naïma , Muller, Sylviane , Munjal, Ashok Kumar , Muñoz‐Cánoves, Pura , Münz, Christian , Muratori, Claudia, Murphy, John Patrick , Nabissi, Massimo , Nah, Jihoon , Nakagawa, Ichiro, Nakatogawa, Hitoshi , Nardacci, Roberta , Narita, Masashi , Neri, Luca Maria , Neufeld, Thomas P. , Nezis, Ioannis P. , Ni, Hong‐Min , Nicolao, María Celeste , Nilsson, Per Gunnar , Ning, Shunbin , Nóbrega, Clévio , Nolan, Trevor M. , Novak, Ivana, Nozawa, Takashi , Nussbaum-Krammer, Carmen I. , O’Sullivan, Timothy E., Oehme, Ina , Ohmuraya, Masaki , Okamoto, Koji , Oku, Masahide, Omary, M. Bishr , Önal, Gizem , Ong, Sang‐Ging , Ortona, Elena , Osta, Rosario , Otegui, Marisa S. , Ottobrini, Luisa , Outeiro, Tiago F. , Øynebråten, Inger , Pajvani, Utpal B. , Pallet, Nicolas , Palumbo, Camilla , Pampaloni, Francesco , Pan, Lifeng , Pan, Wenliang, Pandey, Udai Bhan , Panzarini, Elisa , Papaleo, Elena , Park, Eun Chan , Park, Joon Tae , Park, Sang Chul , Parola, Abraham H. , Parys, Jan B. , Patel, Hemal H. , Patschan, Daniel , Pei, Jianming, Peled‐Zehavi, Hadas , Penna, Fabio , Pérez-Lara, Ángel , Pérez‐Pérez, María Esther , Periyasamy, Palsamy , Perrotta, Cristiana , Perrotta, Ida Daniela , Petersen, Morten , Petrache, Irina , Philips, Jennifer A. , Picca, Anna , Pierdominici, Marina , Pietrocola, Federico , Pignata, Claudio , Pinton, Paolo , Plantinga, Theo S. , Plaza‐Zabala, Ainhoa , Plotnikov, Egor Y. , Plun‐Favreau, Hélène , Pluta, Ryszard , Popova, Blagovesta, Porta, Helena , Post, Martin , Poulton, Joanna , Promponas, Vasilis J. , Proud, Christopher G. , Puri, Rajat , Qi, Xiaopeng , Qian, Wenbin , Qiang, Lei , Qiu, Yu, Quarleri, Jorge Fabián , Ragusa, Michael J. , Rahimi, Nader , Rangarajan, Pundi Narasimhan , Rao, Lang , Rao, Rekha, Razani, Babak , Régnier, Jean-Claude , Reichert, Andreas S , Reue, Karen , Ricci, Jean‐Ehrland , Ricci, Roméo , Rikihisa, Yasuko , Roberts, Helen C., Roberts, Luke D., Roccheri, Maria Carmela , Rodney, George Gerald , Rodrigues, Tiago, Rodrı́guez, Amaia , Barrueco, Ruth Rodriguez , Rodríguez‐Rocha, Humberto , Roelofs, Jeroen , Rolka, Krzysztof , Romeo-Guitart, David , Roperto, Sante , Roth, Kevin A. , Roth, Lynn , Rovere‐Querini, Patrizia , Rubinsztein, David Chaim , Rudolf, Emil, Rudolf, Rüdiger, Ryan, Kevin M. , Ryu, Kwon‐Yul , Sachdev, Ulka , Sacher, Michael, Sadoshima, Junichi , Safren, Nathaniel , Sagona, Antonia P. , Sahay, Gaurav , Sahebkar, Amirhossein , Sahin, Ozgur, Sahni, Sumit , Saito, Shigeru , Sakai, Ryohei , Sanderson, J. Thomas , Sandri, Marco F. , Santaguida, Stefano , Sanz, Alberto, Sanz, Pascual , Sathyanarayanan, Ranganayaki, Schaefer, Liliana , Scharl, Michael M. , Schätzl, Hermann M. , Scheper, Wiep , Scheuring, David , Schott, Micah B. , Schramm, Michael, Schröder, Bernd, Schüller, Christoph, Scialò, Filippo , Sciarretta, Sebastiano , Scovassi, Anna Ivana , Segatori, Laura , Seiliez, Iban , Seki, Ekihiro , Sellke, Frank W. , Sergi, Consolato Maria , Settembre, Carmine , Shao, Changshun , Sheng, Zhi , Shi, Xiaobing , Shimozawa, Makoto, Shoji, Ikuo, Shridhar, Viji , Shu, Hong‐Bing , Sierra, Amanda , Sierra‐Torre, Virginia , Sil, Payel , Simon, Anna Katharina , Simon, Hans‐Uwe , Simons, Matias , Singh, Lalit Pukhrambam , Sirohi, Kapil , Sivridis, Efthimios , Skirycz, Aleksandra , Slaninová, Iva , Smaili, Soraya Soubhi , Smertenko, Andrii , Smith, Matthew D., Soenen, Stefaan J. , Solaini, Giancarlo , Soleimanpour, Scott A. , Solovchenko, Alexei E. , Song, Fuyong, Song, Ju‐Xian , Song, Zhiyin , Soria, Leandro R. , Spagnuolo, Paul A. , Spector, Stephen A. , Stalnecker, Clint A. , Stefan, Katja, Stefanis, Leonidas , Stenmark, Harald , Stevens, Craig, Stoka, Veronika , Stork, Björn , Su, Longxiang , Subauste, Carlos S. , Subbian, Selvakumar , Sun, Jun , Sun, Kang, Sun, Meng‐Xiang , Sun, Qiming , Sun, Yi Ning , Sundberg, Eva , Tabęcka-Łonczyńska, Anna , Tacke, Frank , Tafani, Marco , Tait, Stephen W. G. , Takáts, Szabolcs , Talwar, Priti , Tan, Chong Teik , Tanaka, Motomasa , Tanida, Isei , Tatenhorst, Lars , Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory A., Taylor, Joan M. , Tchetina, Elena V. , Tee, Andrew R. , Tegeder, Irmgard , Teis, David , Teixeira-Clerc, Fatima , Tekirdağ, Kumsal Ayşe, Tepikin, Alexei V. , Testillano, Pilar S. , Tettamanti, Gianluca , Thellung, Stefano , Thomas, Sufi Mary , Thukral, Lipi , Till, Andreas , Todi, Sokol V. , Todorova, Krassimira O. , Tong, Benjamin Chun‐Kit , Tooze, Sharon A. , Torgersen, Maria Lyngaas , Toyokuni, Shinya , Trajković, Vladimir , Tramontano, Donatella , Trelford, Charles B. , Triola, Gemma , Tschan, Mario P. , Tse, Hung‐Fat , Tsugawa, Hitoshi , Tümtaş, Yasin , Tuñón, María Jesús , Turcotte, Sandra , Turk, Boris , Türk, Vito , Turner, Bradley J. , Tuxworth, Richard I. , Unno, Rei , Urbé, Sylvie , Üstün, Şuayib , Vaccari, Thomas , Vakifahmetoglu-Norberg, Helin , Vanrell, María Cristina , Varano, Gabriele , Vavvas, Demetrios G. , Vega‐Naredo, Ignacio , Velotti, Francesca , Vessoni, Alexandre Teixeira , Vidal, Michel, Vierstra, Richard David , Vijayan, Vinoy, Vilar, Marçal , Villarroya, Francesc , Villarroya, Joan , Viscomi, Maria Teresa , Višnjić, Dora , Vitale, Ilio , Wade‐Martins, Richard , Walker, David W., Walker, Simon A. , Walter, Jochen , Wang, Chao-Yung, Wang, Dong , Wang, Fangyang , Wang, Feng , Wang, Guansong , Wang, Han, Wang, Hao , Wang, Jiou , Wang, Lianrong , Wang, Peipei , Wang, Ping, Wang, Qing Jun , Wang, Qing , Wang, Wuyang , Wang, Yan, Wang, Yen‐Yun , Wang, Yipeng , Warnes, Gary , Warnsmann, Verena , Watada, Hirotaka , Wei, Lei , Wells, Alan , Wen, Xin , Wheatley, Sally P. , Whitworth, Alexander J. , Willbold, Dieter , Williams, Roger L. , Winner, Beate , Witkin, Steven Sol , Wong, Esther S.P. , Wong, Jack Ho, Wu, Chengbiao , Wu, Jian Huang , Wu, Mian , Wu, Min , Wu, Shuyan , Wu, Xiaohong , Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xu, Chuanshan , Xu, En, Xu, Haoxing , Xu, Jing , Xu, Wen , Yamaguchi, Osamu , Yan, Shian‐Jang , Yanagi, Yasuo , Yang, Huang‐Tian , Yang, Jin‐Ming , Yang, Pei‐Ming , Yang, Qian , Yang, Xuesong , Yang, Ying , Yao, Honghong , Yao, Shenggen , Yen, Paul M. , Ying, Meidan, Yoo, Young H., Yoshida, Kiyotsugu , Yoshii, Saori R. , Yousefi, Bahman , Yu, Jun Qing , Yu, Jun, Yu, Wai Haung , Yu, Zhou , Yuan, Shyng‐Shiou F. , Yun, Jeanho , Zarbalis, Konstantinos S. , Zhang, Bin , Zhang, Donna D. , Zhang, Hanlin , Zhang, Hong , Zhang, Hui , Zhang, Jianhua , Zhang, Lin , Zhang, Lisheng , Zhang, Wei , Zhang, Xiangnan, Zhang, Xu Dong , Zhang, Yang, Zhang, Yan‐Jin , Zhang, Yingmei , Zhang, Zhengguang , Zhang, Zhihai , Zhang, Zhiyong , Zhao, Xiao-Fan, Zhao, Ying, Zheng, Yi , Zhivotovsky, Boris , Zhou, Ao, Zhou, Hao , Zhou, Hong , Zhou, Jie , Zhou, Jing , Zhou, Jiyong , Zhou, Kailiang , Zhou, Shu‐Feng , Zhou, Zheng-Yu, Zhu, Hongxin, Zhu, Hua , Zhu, Wei‐Guo , Zientara‐Rytter, Katarzyna , Zimmermann, Christine M., Ziviani, Elena , Zwerschke, Werner , Brand‐Saberi, Beate , Li, Zuguo, Oshima, Shigeru , Rong, Yueguang , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767 , Xia, Zhengyuan , Netea, M. G.

Autophagy | March 24, 2021 | Volume: 17 | Issue: 1 | Pages: 1-382

10.1080/15548627.2020.1797280 Get It

Multicenter Study of Long-Term Safety of Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease
Torres, Vicente E. , Chapman, Arlene B., Devuyst, Olivier , Gansevoort, Ron T. , Perrone, Ronald D. , Lee, Jennifer , Hoke, Molly E., Estilo, Alvin, Sergeyeva, Olga, Torres, Vicente E , Torres, Vicente E , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767

Clinical Journal of the American Society of Nephrology | December 29, 2020 | Volume: 16 | Issue: 1 | Pages: 48-58

10.2215/cjn.10250620 Get It

Background and objectives Tolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4, 2-year extension to TEMPO 3:4 (TEMPO 4:4), and 1-year Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, aquaretic adverse events were common. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations occurred in all three studies. Three patients met Hy Law criteria (ALT or AST more than three times and total bilirubin more than two times the upper limit of normal) for severe drug-induced liver injury (two in TEMPO 3:4 and one in TEMPO 4:4). In REPRISE, liver enzyme monitoring frequency was increased to monthly, with no Hy Law cases. A long-term, phase 3 safety study has further characterized tolvaptan safety. Design, setting, participants, & measurements Subjects who completed TEMPO 4:4, REPRISE, or other tolvaptan trials could enroll in this prospective, multinational, open-label safety study. Assessments included monthly liver enzyme testing during the first 18 months of tolvaptan exposure and every 3 months thereafter. Results Among 1803 subjects, median tolvaptan exposure during the extension was 651 days (interquartile range, 538–924), and cumulative exposure (extension and previous trials) was ≤11 years. Subjects entering from REPRISE placebo experienced more aquaretic adverse events compared with subjects from TEMPO 4:4 or REPRISE tolvaptan ( i.e ., patients with prior long-term tolvaptan exposure). Liver enzyme elevations also occurred more frequently in subjects from REPRISE placebo. Percentages experiencing ALT ≥3/≥5/ ≥10/≥20 times the upper limit of normal were 3.2%/2.1%/0.9%/0.7%, respectively, in subjects from REPRISE placebo and 0.6%–1.1%/0.0%–0.1%/0%/0%, respectively, in those from REPRISE tolvaptan and TEMPO 4:4. Percentages experiencing AST ≥3/ ≥5/≥10/≥20 times the upper limit of normal were 6.9%/3.8%/2.3%/0.8%, respectively, in subjects from REPRISE placebo and 0.9%–2.0%/0.0%–1.0%/0%/0%, respectively, in those from REPRISE tolvaptan and TEMPO 4:4. No Hy Law cases occurred. Conclusions No new safety signals emerged during this long-term extension. Monthly liver function testing for the first 18 months of treatment appeared to enable effective detection and management of transaminase elevations. Clinical Trial registry name and registration number: Open Label Extension of TEMPO 3:4, NCT02251275
Can we further enrich autosomal dominant polycystic kidney disease clinical trials for rapidly progressive patients? Application of the PROPKD score in the TEMPO trial
Gall, Émilie Cornec-Le , Blais, Jaime D., Irazabal, María V. , Devuyst, Olivier , Gansevoort, Ron T. , Perrone, R. D., Chapman, Arlene B., Czerwiec, Frank S., Ouyang, John , Heyer, Christina M., Senum, Sarah R. , Meur, Yannick Le , Torres, Vicente E. , Harris, Peter C. , Cornec-Le Gall, Emilie, Harris, Peter C , Torres, Vicente E , Senum, Sarah R , Irazabal, Maria V , Cornec-Le Gall, Emilie , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767

Nephrology Dialysis Transplantation | April 20, 2017 | Volume: 33 | Issue: 4 | Pages: 645-652

10.1093/ndt/gfx188 Get It

Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial
Torres, Vicente E. , Chapman, Arlene B., Devuyst, Olivier , Gansevoort, Ron T. , Dandurand, Ann, Ouyang, John , Czerwiec, Frank S., Blais, Jaime D., Investigators, for the TEMPO 4:4 Trial, Perrone, Ronald D. , Investigators, for the TEMPO 4:4 Trial, Torres, Vicente E , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767

Nephrology Dialysis Transplantation | February 18, 2017 | Volume: 33 | Issue: 3 | Pages: 477-489

10.1093/ndt/gfx043 Get It

Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 Trial
Devuyst, Olivier , Chapman, Arlene B., Gansevoort, Ron T. , Higashihara, Eiji , Torres, Vicente E. , Blais, Jaime D., Zhou, Wen , Ouyang, John , Czerwiec, Frank S., Perrone, Ronald D. , Torres, Vicente E , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767

Journal of the American Society of Nephrology | December 5, 2016 | Volume: 28 | Issue: 5 | Pages: 1592-1602

10.1681/asn.2016040448 Get It

The vasopressin–cAMP–osmolality axis is abnormal in autosomal dominant polycystic kidney disease (ADPKD). In the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 Trial, a 3-year randomized, placebo-controlled trial in adults, the vasopressin V2 receptor antagonist tolvaptan slowed ADPKD progression in patients with preserved GFR. Here, we investigated the determinants of baseline urine osmolality (Uosm) and its value as a severity marker of ADPKD, the factors influencing the response to tolvaptan, and whether change in Uosm associated with key trial end points. At baseline, lower Uosm independently associated with female sex, presence of hypertension, lower eGFR, higher total kidney volume (TKV), and higher age. Tolvaptan consistently reduced Uosm by 200–300 mOsm/kg over 36 months. The Uosm response to tolvaptan depended on baseline eGFR and Uosm. Subjects with greater change in Uosm experienced a significant reduction in clinical progression events. Among subjects receiving tolvaptan, those with a greater suppression of Uosm had slower renal function decline. Assessment at follow-up, off medication, revealed a significant decrease in Uosm in both placebo and treated groups. Tolvaptan significantly increased plasma osmolality, which returned to baseline at follow-up. In conclusion, baseline Uosm in ADPKD reflects age, renal function, and TKV, and baseline Uosm, eGFR, and TKV influence the effect of tolvaptan on Uosm. The greatest renal benefit occurred in subjects achieving greater suppression of Uosm, that is, those with better eGFR at baseline. These results support the link between vasopressin V2 receptor signaling and ADPKD progression.
SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
Li, Man , Weeks, Olivia , Mijatovic, Vladan, Teumer, Alexander , Tromp, Gerard , Fuchsberger, Christian , Gorski, Mathias , Nutile, Teresa , Sedaghat, Sanaz , Sorice, Rossella , Arking, Dan E. , Bihlmeyer, Nathan A. , Böger, Carsten A., Carroll, Robert J. , Cornelis, Marilyn C., Faul, Jessica D. , Feitosa, Mary F. , Gambaro, Giovanni , Gasparini, Paolo , Giulianini, Franco, Heid, Iris M. , Huang, Jinyan , Imboden, Medea , Jeff, Janina M., Jhun, Min A., Katz, Ronit , Kifley, Annette , Kilpeläinen, Tuomas O. , Laakso, Markku , Li‐Gao, Ruifang , Lohman, Kurt, Lu, Yingchang , Mägi, Reedik , Mihailov, Evelin, Mohlke, Karen L. , Mook‐Kanamori, Dennis O. , Robino, Antonietta , Salvi, Erika , Schick, Ursula M., Schulz, Christina‐Alexandra , Smith, Albert V. , Traglia, Michela , Yerges-Armstrong, Laura M. , Goodarzi, Mark O. , Kraja, Aldi T., Wessel, Jennifer , Group,, CHARGE Glycemic-T2D Working, Group,, CHARGE Blood Pressure Working, Boerwinkle, Eric , Borecki, Ingrid B. , Bork‐Jensen, Jette , Böttinger, Erwin P. , Braga, Daniele , Brandslund, Ivan , Brody, Jennifer A. , Carey, David J. , Christensen, Cramer, Crook, Errol D., Boer, Ian H. de , Vries, Aiko P. J. de , Devuyst, Olivier , Dreisbach, Albert W. , Endlich, Karlhans , Franco, Oscar H. , Glümer, Charlotte , Gottesman, Omri, Grarup, Niels , Guðnason, Vilmundur , Harris, Tamara B., Hofman, Albert , Husemoen, Lise Lotte N. , Jackson, Rebecca D. , Jørgensen, Marit E. , Kähönen, Mika , Kardia, Sharon L. R., König, Wolfgang , Kriebel, Jennifer , Lauritzen, Torsten , Lehtimäki, Terho , Levy, Daniel , Linksted, Pamela , Loos, Ruth J. F. , Lupo, Antonio , Meisinger, Christine, Melander, Olle , Mitchell, Paul, Nauck, Matthias, Orho‐Melander, Marju , Parsa, Afshin, Pedersen, Oluf , Peters, Annette , Peters, Ulrike , Polašek, Ozren , Qi, Lu , Reiner, Alex P. , Rettig, Rainer, Ridker, Paul M., Rivadeneira, Fernando , Rossouw, Jacques E. , Schmidt, Frank , Soranzo, Nicole , Strauch, Konstantin , Toniolo, Daniela , Uitterlinden, André G. , Ulivi, Sheila , Velayutham, Dinesh , Völker, Uwe , Völzke, Henry , Waldenberger, Mélanie , Wang, Jie Jin , Weir, David R. , Witte, Daniel R. , Kuivaniemi, Helena , Fox, Caroline S., Franceschini, Nora , Goessling, Wolfram , Köttgen, Anna , Chu, Audrey Y., Rudan, Igor , Vasan, Ramachandran S. , Duijn, Cornelia M. van , Zhao, Wei , Padmanabhan, Sandosh , Lindgren, Cecilia M. , Franks, Paul W. , Weiß, Stefan , Langenberg, Claudia , Hattersley, Andrew T. , Turner, Stephen T. , Li, Yong , Huffman, Jennifer E. , Lyytikäinen, Leo‐Pekka , Tin, Adrienne , Yang, Qiong , Ahluwalia, Tarunveer S. , Chasman, Daniel I. , Dehghan, Abbas , Jackson, Anne , Kumar, Ashish , Malerba, Giovanni , Ruderfer, Douglas , Smith, Jennifer A. , Zhao, Wei , Liu, Chunyu , Group,, CHARGE Glycemic-T2D Working, Group,, CHARGE Blood Pressure Working, Campbell, Archie I , Coresh, Josef , Curhan, Gary C. , Cusi, Daniele , Denny, Joshua C. , Esko, Tõnu , Fülöp, Tibor , Gerhard, Glenn S. , Hansen, Torben , Hayward, Caroline , Hocking, Lynne J. , Hu, Frank B. , Jørgensen, Torben , Kooperberg, Charles , Launer, Lenore J. , Linneberg, Allan , Liu, Ching‐Ti , Meisinger, Christine, Metspalu, Andres , Nürnberg, Peter , Porteous, David John , Probst-Hensch, Nicole M , Psaty, Bruce M. , Raitakari, Olli Tuomas , Siscovick, David S. , Weiss, Stefan , Völker, Uwe , Teumer, Alexander , van Duijn, Cornelia M , Vasan, Ramachandran S , Smith, Albert V , Loos, Ruth J F , Li-Gao, Ruifang , Brody, Jennifer A , Padmanabhan, Sandosh , Levy, Daniel , de Vries, Aiko P J , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767

Journal of the American Society of Nephrology | December 5, 2016 | Volume: 28 | Issue: 3 | Pages: 981-994

10.1681/asn.2016020131 Get It

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 −7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 −8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.
Tolvaptan suppresses monocyte chemotactic protein-1 excretion in autosomal-dominant polycystic kidney disease
Grantham, Jared J. , Chapman, Arlene B., Blais, Jaime D., Czerwiec, Frank S., Devuyst, Olivier , Gansevoort, Ron T. , Higashihara, Eiji , Krasa, Holly B. , Zhou, Wen , Ouyang, John , Torres, Vicente E. , Investigators, for the TEMPO 3:4, Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767 , Gansevoort, Ron T, Zhou, Wen, Perrone, Ronald D. , Torres, Vicente E

Nephrology Dialysis Transplantation | April 15, 2016 | Volume: 32 | Issue: 6 | Pages: 969-975

10.1093/ndt/gfw060 Get It

Abstract Background: Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by multitudes of expanding renal cysts associated with mononuclear interstitial infiltrates. Monocyte chemotactic protein-1 is produced in the kidneys and excreted in the urine (uMCP1) of these patients in increased amounts. In the TEMPO 3:4 trial, tolvaptan slowed the rate of increase in total kidney volume (TKV) and the rate of decline in estimated glomerular filtration rate (eGFR). In a sub-analysis, we determined whether tolvaptan administration for up to 3 years changed the urinary excretion of MCP-1 referenced to creatinine in 869 treated subjects compared with 438 placebo subjects. Methods: Treatment group differences of uMCP1 at 0.75, 12, 24 and 36 months were evaluated by ANCOVA with factor of treatment and covariate baseline. Results: At baseline, mean uMCP1 was 429 ± 224 pg/mg in the tolvaptan and 434 ± 233 pg/mg in the placebo groups, ∼4-fold greater than normal. Log uMCP1 associated positively with log TKV (r = 0.2645, P &lt; 0.0001) and negatively with eGFR (r = −0.1555 P &lt; 0.0001) and fasting urine osmolality (r = −0.1933, P &lt; 0.0001). Tolvaptan reduced uMCP1 13.8 ± 4.4% (P &lt; 0.0001) below placebo-treated subjects at 24 months and 14.4 ± 3.7% (P &lt; 0.0001) at 36 months, and to the same extent in females and males. The effect of tolvaptan on uMCP1 excretion at 36 months extended across CKD Stage 1 (11.1 ± 6.4%, P = 0.0595), CKD 2 (13.9 ± 5.4%, P = 0.0050) and CKD 3 (21.4 ± 8.0%, P = 0.0020). Conclusion: Tolvaptan, administered for 3 years to patients with ADPKD, caused a sustained reduction in the urinary excretion of MCP-1 relative to placebo.