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1. Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Author

Masakazu Kobayashi, Hirohito Sone, Haruhiko Osawa, Daisuke Koya, Takanori Miura, Yoshihito Atsumi, Udai Nakamura, Eiichi Araki, Hitoshi Shimano, Yukio Tanizawa, Jiro Nakamura, Yuichiro Yamada, Nobuya Inagaki, Atsuko Abiko, Hideki Katagiri, Michio Hayashi, Keiko Naruse, Shimpei Fujimoto, Masazumi Fujiwara, Kenichi Shikata, Yosuke Okada, Tsutomu Yamazaki, Sou Nagai, Katsuyuki Yanagisawa, Hiromichi Kijima, Shinji Taneda, Shigeyuki Saitoh, Daisuke Ikeda, Fuminori Hirano, Haruhiko Yoshimura, Mitsutaka Inoue, Masahiko Katoh, Osamu Nakagaki, Chiho Yamamoto, Akitsuki Morikawa, Shin Furukawa, Takeshi Koshiya, Hajime Sugawara, Takumi Uchida, Noe Takakubo, Yasushi Ishigaki, Susumu Suzuki, Takashi Shimotomai, Naoki Tamasawa, Jun Matsui, Takashi Goto, Toshihide Oizumi, Shinji Susa, Makoto Daimon, Hiroshi Murakami, Takashi Sugawara, Hiroaki Akai, Mari Nakamura, Yoshiji Ogawa, Takao Yokoshima, Tsuyoshi Watanabe, Michio Shimabukuro, Kazuhisa Tsukamoto, Motoei Kunimi, Jo Satoh, Atushi Okuyama, Kazutaka Ogawa, Hideyuki Eguchi, Mamoru Kimura, Hiroshi Kouno, Yohei Horikawa, Shin Ikejima, Masaru Saitoh, Naoyoshi Minami, Akihiro Sekikawa, Toyoyoshi Uchida, Toshihide Kawai, Nobuya Fujita, Ken Tomotsune, Shigeo Yamashita, Motoji Naka, Toru Hiyoshi, Tomotaka Katoh, Kumiko Hamano, Kouichi Inukai, Takuma Kondo, Kazuhiro Tsumura, Yoko Matsuzawa, Masahiro Mimura, Masahiko Kawasumi, Izumi Takei, Masafumi Matsuda, Ichiro Tatsuno, Nobuyuki Banba, Akihiko Ando, Masao Toyoda, Daisuke Suzuki, Takahiro Iijima, Yasumichi Mori, Yutaka Uehara, Yoshihiko Satoh, Kazuaki Yahata, Yoshimasa Asoh, Koichiro Kuwabara, Souichi Takizawa, Yasushi Tanaka, Koutaroh Yokote, Masako Tohgo, Takanobu Itoi, Shigeru Miyazaki, Hiroshi Itoh, Teruo Shiba, Takahisa Hirose, Mariko Higa, Masanobu Yamada, Osamu Ogawa, Masatoshi Kuroki, Shinobu Satoh, Makoto Ujihara, Kenjiroh Yamanaka, Hajime Koyano, Tadashi Yamakawa, Kenichiroh Takahashi, Kazuki Orime, Tsutomu Hirano, Jiroh Morimoto, Takashi Itoh, Yuzoh Mizuno, Naoyuki Yamamoto, Han Miyatake, Mina Yamaguchi, Kenji Yamane, Masahiko Kure, Satoko Kawabe, Masahumi Kakei, Masashi Yoshida, Hiroyuki Itoh, Nobuaki Minami, Kazuki Kobayashi, Yusuke Fujino, Makoto Shibuya, Midori Hosokawa, Isao Nozaki, Chigure Nawa, Tamio Ieiri, Takayuki Watanabe, Yoshio Katoh, Takuyuki Katabami, Michiko Handa, Issei Shimada, Kenichi Ohya, Yoshihiro Ogawa, Takanobu Yoshimoto, Jiroh Nakamura, Naotsuka Okayama, Kenro Imaeda, Syuko Yoshioka, Masako Murakami, Takashi Murase, Yoshihiko Yamada, Yutaka Yano, Hiromitsu Sasaki, Yasuhiro Sumida, Osamu Yonaha, Hiroshi Sobajima, Mitsuyasu Ito, Atushi Suzuki, Atsuko Ishikawa, Takehiko Ichikawa, Shogo Asano, Shinobu Goto, Sakuma Hiroya, Hiroshi Murase, Shozo Ogawa, Hideki Okamoto, Kotaro Nagai, Koji Nagayama, Masanori Yoshida, Norio Takahashi, Kazuhisa Takami, Tsuneo Ono, Takanobu Morihiro, Daisuke Tanaka, Noriko Takahara, Satoshi Miyata, Mamiko Tsugawa, Koichiro Yasuda, Seiji Muro, Masanori Emoto, Ikuo Mineo, Ichiro Shiojima, Takeshi Kurose, Makoto Ohashi, Yumiko Kawabata, Mitsushige Nishikawa, Emiko Nomura, Yasuyuki Nishimura, Yasuhiro Ono, Yasuhisa Yamamoto, Keigo Naka, Taizo Yamamoto, Rika Usuda, Hiroshi Akahori, Seika Kato, Hiroyuki Konya, Yutaka Umayahara, Takashi Seta, Hideki Taki, Masashi Sekiya, Shinichi Mogami, Sumie Fujii, Toshiyuki Hibuse, Shingo Tsuji, Hirofumi Sumi, Yasuro Kumeda, Akinori Kogure, Kenji Furukawa, Akira Kuroe, Hideaki Sawaki, Narihiro Hibiki, Yoshihiro Kitagawa, Yukihiro Bando, Akira Ono, Rikako Uenaka, Seitaro Omoto, Yuki Kita, Eiko Ri, Ryutaro Numaguchi, Sachiko Kawashima, Ichiro Kisimoto, Kiminori Hosoda, Yoshihiko Araki, Tetsuroh Arimura, Mitsuru Hashiramoto, Koumei Takeda, Akira Matsutani, Yasushi Inoue, Fumio Sawano, Nozomu Kamei, Yasuo Ito, Miwa Morita, Yoshiaki Oda, Rui Kishimoto, Katsuhiro Hatao, Tomoatsu Mune, Fumiko Kawasaki, Hiroki Teragawa, Ken Yaga, Keita Ishii, Kyouji Hirata, Tatsuaki Nakatou, Yutaka Nitta, Naoki Fujita, Masayasu Yoneda, Masatoshi Tsuru, Shinichirou Ando, Toshiaki Kakiba, Michihiro Toyoshige, Tsuguka Shiwa, Hiroaki Miyaoka, Yasumi Shintani, Takenori Sakai, Tetsuji Niiya, Shinpei Fujimoto, Hisaka Minami, Yoshihiko Noma, Masaaki Tamaru, Yoshitaka Sayou, Tomoyo Oyama, Masamoto Torisu, Yuichi Fujinaka, Yoshitaka Kumon, Shozo Miyauchi, Morikazu Onji, Toru Nakamura, Yousuke Okada, Toshihiko Yanase, Kenro Nishida, Syuji Nakamura, Kunihisa Kobayashi, Nobuhiko Wada, Moritake Higa, Koji Matsushita, Yoshihiko Nishio, Ryoji Fujimoto, Yasuyuki Kihara, Shinichiro Mine, Tadashi Arao, Hiromi Tasaki, Yasuto Matsuo, Hirofumi Matsuda, Kohei Uriu, Kazuko Kanda, Kazuo Ibaraki, Yoshio Kaku, Yasuhiro Takaki, Iwaho Hazekawa, Kenji Ebihara, Eiichiro Watanabe, Iku Sakurada, Kazuhisa Muraishi, Tamami Oshige, Junichi Yasuda, Toyoshi Iguchi, Noriyuki Sonoda, Masahiro Adachi, Isao Ichino, Yuko Horiuchi, Souichi Uekihara, Shingo Morimitsu, Mitsuhiro Nakazawa, Tadashi Seguchi, and Kengo Kaneko

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Published
2021
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2. Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Author

Masakazu Kobayashi, Hirohito Sone, Haruhiko Osawa, Daisuke Koya, Takanori Miura, Yoshihito Atsumi, Udai Nakamura, Eiichi Araki, Hitoshi Shimano, Yukio Tanizawa, Jiro Nakamura, Yuichiro Yamada, Nobuya Inagaki, Atsuko Abiko, Hideki Katagiri, Michio Hayashi, Keiko Naruse, Shimpei Fujimoto, Masazumi Fujiwara, Kenichi Shikata, Yosuke Okada, Tsutomu Yamazaki, Sou Nagai, Katsuyuki Yanagisawa, Hiromichi Kijima, Shinji Taneda, Shigeyuki Saitoh, Daisuke Ikeda, Fuminori Hirano, Haruhiko Yoshimura, Mitsutaka Inoue, Masahiko Katoh, Osamu Nakagaki, Chiho Yamamoto, Akitsuki Morikawa, Shin Furukawa, Takeshi Koshiya, Hajime Sugawara, Takumi Uchida, Noe Takakubo, Yasushi Ishigaki, Susumu Suzuki, Takashi Shimotomai, Naoki Tamasawa, Jun Matsui, Takashi Goto, Toshihide Oizumi, Shinji Susa, Makoto Daimon, Hiroshi Murakami, Takashi Sugawara, Hiroaki Akai, Mari Nakamura, Yoshiji Ogawa, Takao Yokoshima, Tsuyoshi Watanabe, Michio Shimabukuro, Kazuhisa Tsukamoto, Motoei Kunimi, Jo Satoh, Atushi Okuyama, Kazutaka Ogawa, Hideyuki Eguchi, Mamoru Kimura, Hiroshi Kouno, Yohei Horikawa, Shin Ikejima, Masaru Saitoh, Naoyoshi Minami, Akihiro Sekikawa, Toyoyoshi Uchida, Toshihide Kawai, Nobuya Fujita, Ken Tomotsune, Shigeo Yamashita, Motoji Naka, Toru Hiyoshi, Tomotaka Katoh, Kumiko Hamano, Kouichi Inukai, Takuma Kondo, Kazuhiro Tsumura, Yoko Matsuzawa, Masahiro Mimura, Masahiko Kawasumi, Izumi Takei, Masafumi Matsuda, Ichiro Tatsuno, Nobuyuki Banba, Akihiko Ando, Masao Toyoda, Daisuke Suzuki, Takahiro Iijima, Yasumichi Mori, Yutaka Uehara, Yoshihiko Satoh, Kazuaki Yahata, Yoshimasa Asoh, Koichiro Kuwabara, Souichi Takizawa, Yasushi Tanaka, Koutaroh Yokote, Masako Tohgo, Takanobu Itoi, Shigeru Miyazaki, Hiroshi Itoh, Teruo Shiba, Takahisa Hirose, Mariko Higa, Masanobu Yamada, Osamu Ogawa, Masatoshi Kuroki, Shinobu Satoh, Makoto Ujihara, Kenjiroh Yamanaka, Hajime Koyano, Tadashi Yamakawa, Kenichiroh Takahashi, Kazuki Orime, Tsutomu Hirano, Jiroh Morimoto, Takashi Itoh, Yuzoh Mizuno, Naoyuki Yamamoto, Han Miyatake, Mina Yamaguchi, Kenji Yamane, Masahiko Kure, Satoko Kawabe, Masahumi Kakei, Masashi Yoshida, Hiroyuki Itoh, Nobuaki Minami, Kazuki Kobayashi, Yusuke Fujino, Makoto Shibuya, Midori Hosokawa, Isao Nozaki, Chigure Nawa, Tamio Ieiri, Takayuki Watanabe, Yoshio Katoh, Takuyuki Katabami, Michiko Handa, Issei Shimada, Kenichi Ohya, Yoshihiro Ogawa, Takanobu Yoshimoto, Jiroh Nakamura, Naotsuka Okayama, Kenro Imaeda, Syuko Yoshioka, Masako Murakami, Takashi Murase, Yoshihiko Yamada, Yutaka Yano, Hiromitsu Sasaki, Yasuhiro Sumida, Osamu Yonaha, Hiroshi Sobajima, Mitsuyasu Ito, Atushi Suzuki, Atsuko Ishikawa, Takehiko Ichikawa, Shogo Asano, Shinobu Goto, Sakuma Hiroya, Hiroshi Murase, Shozo Ogawa, Hideki Okamoto, Kotaro Nagai, Koji Nagayama, Masanori Yoshida, Norio Takahashi, Kazuhisa Takami, Tsuneo Ono, Takanobu Morihiro, Daisuke Tanaka, Noriko Takahara, Satoshi Miyata, Mamiko Tsugawa, Koichiro Yasuda, Seiji Muro, Masanori Emoto, Ikuo Mineo, Ichiro Shiojima, Takeshi Kurose, Makoto Ohashi, Yumiko Kawabata, Mitsushige Nishikawa, Emiko Nomura, Yasuyuki Nishimura, Yasuhiro Ono, Yasuhisa Yamamoto, Keigo Naka, Taizo Yamamoto, Rika Usuda, Hiroshi Akahori, Seika Kato, Hiroyuki Konya, Yutaka Umayahara, Takashi Seta, Hideki Taki, Masashi Sekiya, Shinichi Mogami, Sumie Fujii, Toshiyuki Hibuse, Shingo Tsuji, Hirofumi Sumi, Yasuro Kumeda, Akinori Kogure, Kenji Furukawa, Akira Kuroe, Hideaki Sawaki, Narihiro Hibiki, Yoshihiro Kitagawa, Yukihiro Bando, Akira Ono, Rikako Uenaka, Seitaro Omoto, Yuki Kita, Eiko Ri, Ryutaro Numaguchi, Sachiko Kawashima, Ichiro Kisimoto, Kiminori Hosoda, Yoshihiko Araki, Tetsuroh Arimura, Mitsuru Hashiramoto, Koumei Takeda, Akira Matsutani, Yasushi Inoue, Fumio Sawano, Nozomu Kamei, Yasuo Ito, Miwa Morita, Yoshiaki Oda, Rui Kishimoto, Katsuhiro Hatao, Tomoatsu Mune, Fumiko Kawasaki, Hiroki Teragawa, Ken Yaga, Keita Ishii, Kyouji Hirata, Tatsuaki Nakatou, Yutaka Nitta, Naoki Fujita, Masayasu Yoneda, Masatoshi Tsuru, Shinichirou Ando, Toshiaki Kakiba, Michihiro Toyoshige, Tsuguka Shiwa, Hiroaki Miyaoka, Yasumi Shintani, Takenori Sakai, Tetsuji Niiya, Shinpei Fujimoto, Hisaka Minami, Yoshihiko Noma, Masaaki Tamaru, Yoshitaka Sayou, Tomoyo Oyama, Masamoto Torisu, Yuichi Fujinaka, Yoshitaka Kumon, Shozo Miyauchi, Morikazu Onji, Toru Nakamura, Yousuke Okada, Toshihiko Yanase, Kenro Nishida, Syuji Nakamura, Kunihisa Kobayashi, Nobuhiko Wada, Moritake Higa, Koji Matsushita, Yoshihiko Nishio, Ryoji Fujimoto, Yasuyuki Kihara, Shinichiro Mine, Tadashi Arao, Hiromi Tasaki, Yasuto Matsuo, Hirofumi Matsuda, Kohei Uriu, Kazuko Kanda, Kazuo Ibaraki, Yoshio Kaku, Yasuhiro Takaki, Iwaho Hazekawa, Kenji Ebihara, Eiichiro Watanabe, Iku Sakurada, Kazuhisa Muraishi, Tamami Oshige, Junichi Yasuda, Toyoshi Iguchi, Noriyuki Sonoda, Masahiro Adachi, Isao Ichino, Yuko Horiuchi, Souichi Uekihara, Shingo Morimitsu, Mitsuhiro Nakazawa, Tadashi Seguchi, and Kengo Kaneko

Subjects
Blood Glucose, safety, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Hypoglycemia, Group B, Diseases of the endocrine glands. Clinical endocrinology, dipeptidyl peptidase 4, Japan, Piperidines, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Prospective Studies, Adverse effect, Uracil, Aged, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Incidence (epidemiology), Type 2 Diabetes Mellitus, registries, medicine.disease, RC648-665, Diabetes Mellitus, Type 2, type 2, diabetes mellitus, Clinical care/Education/Nutrition, business, Alogliptin
Abstract

IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Published
2020

3. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Author

Hiddo J L Heerspink, Hans-Henrik Parving, Dennis L Andress, George Bakris, Ricardo Correa-Rotter, Fan-Fan Hou, Dalane W Kitzman, Donald Kohan, Hirofumi Makino, John J V McMurray, Joel Z Melnick, Michael G Miller, Pablo E Pergola, Vlado Perkovic, Sheldon Tobe, Tingting Yi, Melissa Wigderson, Dick de Zeeuw, Alicia Elbert, Augusto Vallejos, Andres Alvarisqueta, Laura Maffei, Luis Juncos, Javier de Arteaga, Gustavo Greloni, Eduardo Farias, Alfredo Zucchini, Daniel Vogel, Ana Cusumano, Juan Santos, Margaret Fraenkel, Martin Gallagher, Tim Davis, Shamasunder Acharya, Duncan Cooke, Michael Suranyi, Simon Roger, Nigel Toussaint, Carol Pollock, Doris Chan, Stephen Stranks, Richard MacIsaac, Zoltan Endre, Alice Schmidt, Rudolf Prager, Gert Mayer, Xavier Warling, Michel Jadoul, Jean Hougardy, Chris Vercammen, Bruno Van Vlem, Pieter Gillard, Adriana Costa e Forti, Joao Lindolfo Borges, Luis Santos Canani, Freddy Eliaschewitz, Silmara Leite, Fadlo Fraige Filho, Raphael Paschoalin, Jose Andrade Moura Neto, Luciane Deboni, Irene de Lourdes Noronha, Cintia Cercato, Carlos Alberto Prompt, Maria Zanella, Nelson Rassi, Domingos D'Avila, Rosangela Milagres, Joao Felicio, Roberto Pecoits Filho, Miguel Carlos Riella, Joao Salles, Elizete Keitel, Sergio Draibe, Celso Amodeo, Joseph Youmbissi, Louise Roy, Serge Cournoyer, Shivinder Jolly, Vincent Pichette, Gihad Nesrallah, Harpreet Singh Bajaj, Hasnain Khandwala, Ronnie Aronson, Richard Goluch, Paul Tam, Christian Rabbat, Gordon Bailey, Stephen Chow, Alvaro Castillo, Alfredo Danin Vargas, Fernando Gonzalez, Rodrigo Munoz, Vicente Gutierrez, Gonzalo Godoy, Hongwen Zhao, Zhangsuo Liu, Minghui Zhao, Xiaohui Guo, Benli Su, Shuxia Fu, Yan Xu, Jinkui Yang, Bingyin Shi, Guanqing Xiao, Wei Shi, Chuanming Hao, Changying Xing, Fanfan Hou, Qun Luo, Yuxiu Li, Linong Ji, Li Zuo, Song Wang, Zhaohui Ni, Guohua Ding, Nan Chen, Jiajun Zhao, Weiping Jia, Shengqiang Yu, Jian Weng, Gang Xu, Ping Fu, Shiren Sun, Bicheng Liu, Xiaoqiang Ding, Ivan Rychlik, Alexandra Oplustilova, Dagmar Bartaskova, Vaclava Honova, Hana Chmelickova, Martin Petr, Petr Bucek, Vladimir Tesar, Emil Zahumensky, Johan Povlsen, Kenneth Egstrup, Anna Oczachowska-Kulik, Peter Rossing, Jorma Lahtela, Jorma Strand, Ilkka Kantola, Catherine Petit, Christian Combe, Philippe Zaoui, Vincent Esnault, Pablo Urena Torres, Jean-Michel Halimi, Bertrand Dussol, Tasso Bieler, Klemens Budde, Frank Dellanna, Thomas Segiet, Christine Kosch, Hans Schmidt-Guertler, Isabelle Schenkenberger, Volker Vielhauer, Frank Pistrosch, Mark Alscher, Christoph Hasslacher, Christian Hugo, Anja Muehlfeld, Christoph Wanner, Ploumis Passadakis, Theofanis Apostolou, Nikolaos Tentolouris, Ioannis Stefanidis, Konstantinos Mavromatidis, Vasilios Liakopoulos, Dimitrios Goumenos, Konstantinos Siamopoulos, Vincent Yeung, Risa Ozaki, Samuel Fung, Kathryn Tan, Sydney Tang, Sing Leung Lui, Siu Fai Cheung, Seamus Sreenan, Joseph Eustace, Donal O'Shea, Peter Lavin, Austin Stack, Yoram Yagil, Julio Wainstein, Hilla Knobler, Josef Cohen, Irina Kenis, Deeb Daoud, Yosefa Bar-Dayan, Victor Frajewicki, Faiad Adawi, Loreto Gesualdo, Domenico Santoro, Francesco Marino, Andrea Galfre, Chiara Brunati, Piero Ruggenenti, Giuseppe Rombola, Giuseppe Pugliese, Maura Ravera, Fabio Malberti, Giuseppe Pontoriero, Teresa Rampino, Salvatore De Cosmo, Ciro Esposito, Felice Nappi, Cataldo Abaterusso, Giuseppe Conte, Vincenzo Panichi, Davide Lauro, Giovambattista Capasso, Domenico Russo, Jiichi Anzai, Motoji Naka, Keita Ato, Tetsuro Tsujimoto, Toshinori Nimura, Eitaro Nakashima, Tetsuro Takeda, Shinya Fujii, Kunihisa Kobayashi, Hideaki Iwaoka, Koji Nagayama, Hiroyuki Harada, Hajime Maeda, Rui Kishimoto, Tadashi Iitsuka, Naoki Itabashi, Ryuichi Furuya, Yoshitaka Maeda, Daishiro Yamada, Nobuhiro Sasaki, Hiromitsu Sasaki, Shinichiro Ueda, Naoki Kashihara, Shuichi Watanabe, Takehiro Nakamura, Hidetoshi Kanai, Yuichiro Makita, Keiko Ono, Noriyuki Iehara, Daisuke Goto, Keiichiro Kosuge, Kenichi Tsuchida, Toshiaki Sato, Takashi Sekikawa, Hideki Okamoto, Tsuyoshi Tanaka, Naoko Ikeda, Takenobu Tadika, Koji Mukasa, Takeshi Osonoi, Fuminori Hirano, Motonobu Nishimura, Yuko Yambe, Yukio Tanaka, Makoto Ujihara, Takashi Sakai, Mitsuo Imura, Yutaka Umayahara, Shinya Makino, Jun Nakazawa, Yukinari Yamaguchi, Susumu Kashine, Hiroaki Miyaoka, Katsunori Suzuki, Toshihiko Inoue, Sou Nagai, Nobuyuki Sato, Masahiro Yamamoto, Noriyasu Taya, Akira Fujita, Akira Matsutani, Yugo Shibagaki, Yuichi Sato, Akira Yamauchi, Masahiro Tsutsui, Tamayo Ishiko, Shizuka Kaneko, Nobuyuki Azuma, Hirofumi Matsuda, Yasuhiro Hashiguchi, Yukiko Onishi, Mikiya Tokui, Munehide Matsuhisa, Arihiro Kiyosue, Junji Shinoda, Kazuo Ishikawa, Ghazali Ahmad, Shalini Vijayasingham, Nor Azizah Aziz, Zanariah Hussein, Yin Khet Fung, Wan Hasnul Halimi Wan Hassan, Hin Seng Wong, Bak Leong Goh, Norhaliza Mohd Ali, Nor Shaffinaz Yusuf Azmi Merican, Indralingam Vaithilingam, Nik Nur Fatnoon Nik Ahmad, Noor Adam, Norlela Sukor, V Paranthaman P Vengadasalam, Khalid Abdul Kadir, Mafauzy Mohamed, Karina Renoirte Lopez, Aniceto Leguizamo-Dimas, Alfredo Chew Wong, Jose Chevaile-Ramos, Jose Gonzalez Gonzalez, Raul Rico Hernandez, Jose Nino-Cruz, Leobardo Sauque Reyna, Guillermo Gonzalez-Galvez, Magdalena Madero Rovalo, Tomasso Bochicchio-Ricardelli, Jorge Aldrete, Jaime Carranza-Madrigal, Liffert Vogt, Peter Smak Gregoor, JNM Barendregt, Peter Luik, Ronald Gansevoort, Gozewijn Laverman, Helen Pilmore, Helen Lunt, John Baker, Steven Miller, Kannaiyan Rabindranath, Luis Zapata-Rincon, Rolando Vargas-Gonzales, Jorge Calderon Ticona, Augusto Dextre Espinoza, Jose Burga Nunez, Carlos Antonio Zea-Nunez, Benjamin Herrada Orue, Boris Medina-Santander, Cesar Delgado-Butron, Julio Farfan-Aspilcueta, Stanislaw Mazur, Miroslaw Necki, Michal Wruk, Katarzyna Klodawska, Grazyna Popenda, Ewa Skokowska, Malgorzata Arciszewska, Andrzej Wiecek, Kazimierz Ciechanowski, Michal Nowicki, Rita Birne, Antonio Cabrita, Aura Ramos, Manuel Anibal Antunes Ferreira, Evelyn Matta Fontanet, Altagracia Aurora Alcantara-Gonzalez, Angel Comulada-Rivera, Eugenia Galindo Ramos, Jose Cangiano, Luis Quesada-Suarez, Ricardo Calderon Ortiz, Jose Vazquez-Tanus, Rafael Burgos-Calderon, Carlos Rosado, Nicolae Hancu, Ella Pintilei, Cristina Mistodie, Gabriel Bako, Lavinia Ionutiu, Ligia Petrica, Romulus Timar, Liliana Tuta, Livia Duma, Adriana Tutescu, Svetlana Ivanova, Ashot Essaian, Konstantin Zrazhevskiy, Natalia Tomilina, Elena Smolyarchuk, Anatoly Kuzin, Olga Lantseva, Irina Karpova, Minara Shamkhalova, Natalia Liberanskaya, Andrey Yavdosyuk, Yuri Shvarts, Tatiana Bardymova, Olga Blagoveshchenskaya, Oleg Solovev, Elena Rechkova, Natalia Pikalova, Maria Pavlova, Elena Kolmakova, Rustam Sayfutdinov, Svetlana Villevalde, Natalya Koziolova, Vladimir Martynenko, Vyacheslav Marasaev, Adelya Maksudova, Olga Sigitova, Viktor Mordovin, Vadim Klimontov, Yulia Samoylova, Tatiana Karonova, Lee Ying Yeoh, Boon Wee Teo, Marjorie Wai Yin Foo, Adrian Liew, Ivan Tkac, Aniko Oroszova, Jozef Fekete, Jaroslav Rosenberger, Ida Obetkova, Alla Fulopova, Eva Kolesarova, Katarina Raslova, Peter Smolko, Adrian Oksa, Larry Distiller, Julien Trokis, Luthando Adams, Hemant Makan, Padaruth Ramlachan, Essack Mitha, Kathleen Coetzee, Zelda Punt, Qasim Bhorat, Puvenesvari Naiker, Graham Ellis, Louis Van Zyl, Kwan Woo Lee, Min Seon Kim, Soon-Jib Yoo, Kun Ho Yoon, Yong-Wook Cho, Tae-Sun Park, Sang Yong Kim, Moon-Gi Choi, Tae Keun Oh, Kang-Wook Lee, Ho Sang Shon, Sung Hwan Suh, Byung-Joon Kim, Kim Doo-Man, Joo Hark Yi, Sang Ah Lee, Ho Chan Cho, Sin-Gon Kim, Dae-Ryong Cha, Ji A Seo, Kyung Mook Choi, Jeong-Taek Woo, Kyu Jeung Ahn, Jae Hyuk Lee, In-Joo Kim, Moon-Kyu Lee, Hak Chul Jang, Kyong-Soo Park, Beom Seok Kim, Ji Oh Mok, Mijung Shin, Sun Ae Yoon, Il-Seong Nam-Goong, Choon Hee Chung, Tae Yang Yu, Hyoung Woo Lee, Alfonso Soto Gonzalez, Jaume Almirall, Jesus Egido, Francesca Calero Gonzalez, Gema Fernandez Fresnedo, Ildefonso Valera Cortes, Manuel Praga Terente, Isabel Garcia Mendez, Juan Navarro Gonzalez, Jose Herrero Calvo, Secundino Cigarran Guldris, Mario Prieto Velasco, Jose Ignacio Minguela Pesquera, Antonio Galan, Julio Pascual, Maria Marques Vidas, Judith Martins Munoz, Jose Rodriguez-Perez, Cristina Castro-Alonso, Josep Bonet Sol, Daniel Seron, Elvira Fernandez Giraldez, Javier Arrieta Lezama, Nuria Montero, Julio Hernandez-Jaras, Rafael Santamaria Olmo, Jose Ramon Molas Coten, Olof Hellberg, Bengt Fellstrom, Andreas Bock, Dee Pei, Ching-Ling Lin, Kai-Jen Tien, Ching-Chu Chen, Chien-Ning Huang, Ju-Ying Jiang, Du-An Wu, Chih-Hsun Chu, Shih-Ting Tseng, Jung-Fu Chen, Cho-Tsan Bau, Wayne Sheu, Mai-Szu Wu, Ramazan Sari, Siren Sezer, Alaattin Yildiz, Ilhan Satman, Betul Kalender, Borys Mankovskyy, Ivan Fushtey, Mykola Stanislavchuk, Mykola Kolenyk, Iryna Dudar, Viktoriia Zolotaikina, Orest Abrahamovych, Tetyana Kostynenko, Olena Petrosyan, Petro Kuskalo, Olga Galushchak, Oleg Legun, Ivan Topchii, Liliya Martynyuk, Vasyl Stryzhak, Svitlana Panina, Sergii Tkach, Vadym Korpachev, Peter Maxwell, Luigi Gnudi, Sui Phin Kon, Hilary Tindall, Phillip Kalra, Patrick Mark, Dipesh Patel, Mohamed El-Shahawy, Liqun Bai, Romanita Nica, Yeong-Hau Lien, Judson Menefee, Robert Busch, Alan Miller, Azazuddin Ahmed, Ahmed Arif, Joseph Lee, Sachin Desai, Shweta Bansal, Marie Bentsianov, Mario Belledonne, Charles Jere, Raul Gaona, Gregory Greenwood, Osvaldo Brusco, Mark Boiskin, Diogo Belo, Raffi Minasian, Naveen Atray, Mary Lawrence, John Taliercio, Pablo Pergola, David Scott, German Alvarez, Bradley Marder, Thomas Powell, Wa'el Bakdash, George Stoica, Christopher McFadden, Marc Rendell, Jonathan Wise, Audrey Jones, Michael Jardula, Ivy-Joan Madu, Freemu Varghese, Brian Tulloch, Ziauddin Ahmed, Melanie Hames, Imran Nazeer, Newman Shahid, Rekha John, Manuel Montero, David Fitz-Patrick, Lawrence Phillips, Antonio Guasch, Elena Christofides, Aijaz Gundroo, Mohammad Amin, Cynthia Bowman-Stroud, Michael Link, Laura Mulloy, Michael Nammour, Tarik Lalwani, Lenita Hanson, Adam Whaley-Connell, Lee Herman, Rupi Chatha, Sayed Osama, Kenneth Liss, Zeid Kayali, Anuj Bhargava, Ezra Israel, Alfredo Peguero-Rivera, Michael Fang, Judith Slover, Elena Barengolts, Jose Flores, Rosemary Muoneke, Virginia Savin, Stella Awua-Larbi, Andrew Levine, George Newman, Laden Golestaneh, Guillermo Bohm, Efrain Reisin, Lucita Cruz, Robert Weiss, Franklin Zieve, Edward Horwitz, Peale Chuang, James Mersey, John Manley, Ronald Graf, Fadi Bedros, Sudhir Joshi, Juan Frias, Ali Assefi, Andrew O'Shaughnessy, Roman Brantley, Todd Minga, David Tietjen, Samuel Kantor, Aamir Jamal, Ramon Guadiz, Kenneth Hershon, Peter Bressler, Nelson Kopyt, Harold Cathcart, Scott Bloom, Ronald Reichel, Samer Nakhle, Emily Dulude, Joshua Tarkan, Penelope Baker, Steven Zeig, Jaynier Moya Hechevarria, Armando Ropero-Cartier, Gilda De la Calle, Ankur Doshi, Fadi Saba, Teresa Sligh, Sylvia Shaw, Jayant Kumar, Harold Szerlip, George Bayliss, Alan Perlman, Lakhi Sakhrani, Steven Gouge, Georges Argoud, Idalia Acosta, John Elder, Sucharit Joshi, John Sensenbrenner, Steven Vicks, Roberto Mangoo-Karim, Claude Galphin, Carlos Leon-Forero, John Gilbert, Eric Brown, Adeel Ijaz, Salman Butt, Mariana Markell, Carlos Arauz-Pacheco, Lance Sloan, Odilon Alvarado, Serge Jabbour, Eric Simon, Anjay Rastogi, Sam James, Karen Hall, John Melish, Brad Dixon, Allen Adolphe, Csaba Kovesdy, Srinivasan Beddhu, Richard Solomon, Ronald Fernando, Ellis Levin, Charuhas Thakar, Brooks Robey, David Goldfarb, Linda Fried, Geetha Maddukuri, Stephen Thomson, Andrew Annand, Saeed Kronfli, Paramjit Kalirao, Rebecca Schmidt, Neera Dahl, Samuel Blumenthal, Debra Weinstein, Ove Ostergaard, Talia Weinstein, Yasuhiro Ono, Murat Yalcin, Shahana Karim, APH - Health Behaviors & Chronic Diseases, Nephrology, ACS - Amsterdam Cardiovascular Sciences, ACS - Microcirculation, Biomedical Signals and Systems, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Heerspink, H. J. L., Parving, H. -H., Andress, D. L., Bakris, G., Correa-Rotter, R., Hou, F. -F., Kitzman, D. W., Kohan, D., Makino, H., Mcmurray, J. J. V., Melnick, J. Z., Miller, M. G., Pergola, P. E., Perkovic, V., Tobe, S., Yi, T., Wigderson, M., de Zeeuw, D., Elbert, A., Vallejos, A., Alvarisqueta, A., Maffei, L., Juncos, L., de Arteaga, J., Greloni, G., Farias, E., Zucchini, A., Vogel, D., Cusumano, A., Santos, J., Fraenkel, M., Gallagher, M., Davis, T., Acharya, S., Cooke, D., Suranyi, M., Roger, S., Toussaint, N., Pollock, C., Chan, D., Stranks, S., Macisaac, R., Endre, Z., Schmidt, A., Prager, R., Mayer, G., Warling, X., Jadoul, M., Hougardy, J., Vercammen, C., Van Vlem, B., Gillard, P., Costa e Forti, A., Borges, J. L., Santos Canani, L., Eliaschewitz, F., Leite, S., Fraige Filho, F., Paschoalin, R., Moura Neto, J. A., Deboni, L., de Lourdes Noronha, I., Cercato, C., Prompt, C. A., Zanella, M., Rassi, N., D'Avila, D., Milagres, R., Felicio, J., Pecoits Filho, R., Riella, M. C., Salles, J., Keitel, E., Draibe, S., Amodeo, C., Youmbissi, J., Roy, L., Cournoyer, S., Jolly, S., Pichette, V., Nesrallah, G., Bajaj, H. S., Khandwala, H., Aronson, R., Goluch, R., Tam, P., Rabbat, C., Bailey, G., Chow, S., Castillo, A., Danin Vargas, A., Gonzalez, F., Munoz, R., Gutierrez, V., Godoy, G., Zhao, H., Liu, Z., Zhao, M., Guo, X., Su, B., Fu, S., Xu, Y., Yang, J., Shi, B., Xiao, G., Shi, W., Hao, C., Xing, C., Hou, F., Luo, Q., Li, Y., Ji, L., Zuo, L., Wang, S., Ni, Z., Ding, G., Chen, N., Zhao, J., Jia, W., Yu, S., Weng, J., Xu, G., Fu, P., Sun, S., Liu, B., Ding, X., Rychlik, I., Oplustilova, A., Bartaskova, D., Honova, V., Chmelickova, H., Petr, M., Bucek, P., Tesar, V., Zahumensky, E., Povlsen, J., Egstrup, K., Oczachowska-Kulik, A., Rossing, P., Lahtela, J., Strand, J., Kantola, I., Petit, C., Combe, C., Zaoui, P., Esnault, V., Urena Torres, P., Halimi, J. -M., Dussol, B., Bieler, T., Budde, K., Dellanna, F., Segiet, T., Kosch, C., Schmidt-Guertler, H., Schenkenberger, I., Vielhauer, V., Pistrosch, F., Alscher, M., Hasslacher, C., Hugo, C., Muehlfeld, A., Wanner, C., Passadakis, P., Apostolou, T., Tentolouris, N., Stefanidis, I., Mavromatidis, K., Liakopoulos, V., Goumenos, D., Siamopoulos, K., Yeung, V., Ozaki, R., Fung, S., Tan, K., Tang, S., Lui, S. L., Cheung, S. F., Sreenan, S., Eustace, J., O'Shea, D., Lavin, P., Stack, A., Yagil, Y., Wainstein, J., Knobler, H., Cohen, J., Kenis, I., Daoud, D., Bar-Dayan, Y., Frajewicki, V., Adawi, F., Gesualdo, L., Santoro, D., Marino, F., Galfre, A., Brunati, C., Ruggenenti, P., Rombola, G., Pugliese, G., Ravera, M., Malberti, F., Pontoriero, G., Rampino, T., De Cosmo, S., Esposito, C., Nappi, F., Abaterusso, C., Conte, G., Panichi, V., Lauro, D., Capasso, G., Russo, D., Anzai, J., Naka, M., Ato, K., Tsujimoto, T., Nimura, T., Nakashima, E., Takeda, T., Fujii, S., Kobayashi, K., Iwaoka, H., Nagayama, K., Harada, H., Maeda, H., Kishimoto, R., Iitsuka, T., Itabashi, N., Furuya, R., Maeda, Y., Yamada, D., Sasaki, N., Sasaki, H., Ueda, S., Kashihara, N., Watanabe, S., Nakamura, T., Kanai, H., Makita, Y., Ono, K., Iehara, N., Goto, D., Kosuge, K., Tsuchida, K., Sato, T., Sekikawa, T., Okamoto, H., Tanaka, T., Ikeda, N., Tadika, T., Mukasa, K., Osonoi, T., Hirano, F., Nishimura, M., Yambe, Y., Tanaka, Y., Ujihara, M., Sakai, T., Imura, M., Umayahara, Y., Makino, S., Nakazawa, J., Yamaguchi, Y., Kashine, S., Miyaoka, H., Suzuki, K., Inoue, T., Nagai, S., Sato, N., Yamamoto, M., Taya, N., Fujita, A., Matsutani, A., Shibagaki, Y., Sato, Y., Yamauchi, A., Tsutsui, M., Ishiko, T., Kaneko, S., Azuma, N., Matsuda, H., Hashiguchi, Y., Onishi, Y., Tokui, M., Matsuhisa, M., Kiyosue, A., Shinoda, J., Ishikawa, K., Ahmad, G., Vijayasingham, S., Aziz, N. A., Hussein, Z., Fung, Y. K., Hassan, W. H. H. W., Wong, H. S., Goh, B. L., Ali, N. M., Merican, N. S. Y. A., Vaithilingam, I., Nik Ahmad, N. N. F., Adam, N., Sukor, N., Vengadasalam, V. P. P., Abdul Kadir, K., Mohamed, M., Renoirte Lopez, K., Leguizamo-Dimas, A., Chew Wong, A., Chevaile-Ramos, J., Gonzalez Gonzalez, J., Rico Hernandez, R., Nino-Cruz, J., Sauque Reyna, L., Gonzalez-Galvez, G., Madero Rovalo, M., Bochicchio-Ricardelli, T., Aldrete, J., Carranza-Madrigal, J., Vogt, L., Smak Gregoor, P., Barendregt, J. N. M., Luik, P., Gansevoort, R., Laverman, G., Pilmore, H., Lunt, H., Baker, J., Miller, S., Rabindranath, K., Zapata-Rincon, L., Vargas-Gonzales, R., Calderon Ticona, J., Dextre Espinoza, A., Burga Nunez, J., Zea-Nunez, C. A., Herrada Orue, B., Medina-Santander, B., Delgado-Butron, C., Farfan-Aspilcueta, J., Mazur, S., Necki, M., Wruk, M., Klodawska, K., Popenda, G., Skokowska, E., Arciszewska, M., Wiecek, A., Ciechanowski, K., Nowicki, M., Birne, R., Cabrita, A., Ramos, A., Antunes Ferreira, M. A., Matta Fontanet, E., Alcantara-Gonzalez, A. A., Comulada-Rivera, A., Galindo Ramos, E., Cangiano, J., Quesada-Suarez, L., Calderon Ortiz, R., Vazquez-Tanus, J., Burgos-Calderon, R., Rosado, C., Hancu, N., Pintilei, E., Mistodie, C., Bako, G., Ionutiu, L., Petrica, L., Timar, R., Tuta, L., Duma, L., Tutescu, A., Ivanova, S., Essaian, A., Zrazhevskiy, K., Tomilina, N., Smolyarchuk, E., Kuzin, A., Lantseva, O., Karpova, I., Shamkhalova, M., Liberanskaya, N., Yavdosyuk, A., Shvarts, Y., Bardymova, T., Blagoveshchenskaya, O., Solovev, O., Rechkova, E., Pikalova, N., Pavlova, M., Kolmakova, E., Sayfutdinov, R., Villevalde, S., Koziolova, N., Martynenko, V., Marasaev, V., Maksudova, A., Sigitova, O., Mordovin, V., Klimontov, V., Samoylova, Y., Karonova, T., Yeoh, L. Y., Teo, B. W., Foo, M. W. Y., Liew, A., Tkac, I., Oroszova, A., Fekete, J., Rosenberger, J., Obetkova, I., Fulopova, A., Kolesarova, E., Raslova, K., Smolko, P., Oksa, A., Distiller, L., Trokis, J., Adams, L., Makan, H., Ramlachan, P., Mitha, E., Coetzee, K., Punt, Z., Bhorat, Q., Naiker, P., Ellis, G., Van Zyl, L., Lee, K. W., Kim, M. S., Yoo, S. -J., Yoon, K. H., Cho, Y. -W., Park, T. -S., Kim, S. Y., Choi, M. -G., Oh, T. K., Lee, K. -W., Shon, H. S., Suh, S. H., Kim, B. -J., Doo-Man, K., Yi, J. H., Lee, S. A., Cho, H. C., Kim, S. -G., Cha, D. -R., Seo, J. A., Choi, K. M., Woo, J. -T., Ahn, K. J., Lee, J. H., Kim, I. -J., Lee, M. -K., Jang, H. C., Park, K. -S., Kim, B. S., Mok, J. O., Shin, M., Yoon, S. A., Nam-Goong, I. -S., Chung, C. H., Yu, T. Y., Lee, H. W., Soto Gonzalez, A., Almirall, J., Egido, J., Calero Gonzalez, F., Fernandez Fresnedo, G., Valera Cortes, I., Praga Terente, M., Garcia Mendez, I., Navarro Gonzalez, J., Herrero Calvo, J., Cigarran Guldris, S., Prieto Velasco, M., Minguela Pesquera, J. I., Galan, A., Pascual, J., Marques Vidas, M., Martins Munoz, J., Rodriguez-Perez, J., Castro-Alonso, C., Bonet Sol, J., Seron, D., Fernandez Giraldez, E., Arrieta Lezama, J., Montero, N., Hernandez-Jaras, J., Santamaria Olmo, R., Molas Coten, J. R., Hellberg, O., Fellstrom, B., Bock, A., Pei, D., Lin, C. -L., Tien, K. -J., Chen, C. -C., Huang, C. -N., Jiang, J. -Y., Wu, D. -A., Chu, C. -H., Tseng, S. -T., Chen, J. -F., Bau, C. -T., Sheu, W., Wu, M. -S., Sari, R., Sezer, S., Yildiz, A., Satman, I., Kalender, B., Mankovskyy, B., Fushtey, I., Stanislavchuk, M., Kolenyk, M., Dudar, I., Zolotaikina, V., Abrahamovych, O., Kostynenko, T., Petrosyan, O., Kuskalo, P., Galushchak, O., Legun, O., Topchii, I., Martynyuk, L., Stryzhak, V., Panina, S., Tkach, S., Korpachev, V., Maxwell, P., Gnudi, L., Kon, S. P., Tindall, H., Kalra, P., Mark, P., Patel, D., El-Shahawy, M., Bai, L., Nica, R., Lien, Y. -H., Menefee, J., Busch, R., Miller, A., Ahmed, A., Arif, A., Lee, J., Desai, S., Bansal, S., Bentsianov, M., Belledonne, M., Jere, C., Gaona, R., Greenwood, G., Brusco, O., Boiskin, M., Belo, D., Minasian, R., Atray, N., Lawrence, M., Taliercio, J., Pergola, P., Scott, D., Alvarez, G., Marder, B., Powell, T., Bakdash, W., Stoica, G., Mcfadden, C., Rendell, M., Wise, J., Jones, A., Jardula, M., Madu, I. -J., Varghese, F., Tulloch, B., Ahmed, Z., Hames, M., Nazeer, I., Shahid, N., John, R., Montero, M., Fitz-Patrick, D., Phillips, L., Guasch, A., Christofides, E., Gundroo, A., Amin, M., Bowman-Stroud, C., Link, M., Mulloy, L., Nammour, M., Lalwani, T., Hanson, L., Whaley-Connell, A., Herman, L., Chatha, R., Osama, S., Liss, K., Kayali, Z., Bhargava, A., Israel, E., Peguero-Rivera, A., Fang, M., Slover, J., Barengolts, E., Flores, J., Muoneke, R., Savin, V., Awua-Larbi, S., Levine, A., Newman, G., Golestaneh, L., Bohm, G., Reisin, E., Cruz, L., Weiss, R., Zieve, F., Horwitz, E., Chuang, P., Mersey, J., Manley, J., Graf, R., Bedros, F., Joshi, S., Frias, J., Assefi, A., O'Shaughnessy, A., Brantley, R., Minga, T., Tietjen, D., Kantor, S., Jamal, A., Guadiz, R., Hershon, K., Bressler, P., Kopyt, N., Cathcart, H., Bloom, S., Reichel, R., Nakhle, S., Dulude, E., Tarkan, J., Baker, P., Zeig, S., Moya Hechevarria, J., Ropero-Cartier, A., De la Calle, G., Doshi, A., Saba, F., Sligh, T., Shaw, S., Kumar, J., Szerlip, H., Bayliss, G., Perlman, A., Sakhrani, L., Gouge, S., Argoud, G., Acosta, I., Elder, J., Sensenbrenner, J., Vicks, S., Mangoo-Karim, R., Galphin, C., Leon-Forero, C., Gilbert, J., Brown, E., Ijaz, A., Butt, S., Markell, M., Arauz-Pacheco, C., Sloan, L., Alvarado, O., Jabbour, S., Simon, E., Rastogi, A., James, S., Hall, K., Melish, J., Dixon, B., Adolphe, A., Kovesdy, C., Beddhu, S., Solomon, R., Fernando, R., Levin, E., Thakar, C., Robey, B., Goldfarb, D., Fried, L., Maddukuri, G., Thomson, S., Annand, A., Kronfli, S., Kalirao, P., Schmidt, R., Dahl, N., Blumenthal, S., Weinstein, D., Ostergaard, O., Weinstein, T., Ono, Y., Yalcin, M., Karim, S., Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic

Subjects
Male, endothelin, albuminuria, nephropathy, inhibition, Diabetes Mellitus, Type 2/drug therapy, Endocrinology, Diabetes and Metabolism, Placebo-controlled study, Administration, Oral, 030204 cardiovascular system & hematology, Settore MED/13 - Endocrinologia, chemistry.chemical_compound, 0302 clinical medicine, ENDOTHELIN, 80 and over, Diabetic Nephropathies, 030212 general & internal medicine, Renal Insufficiency, Chronic, Aged, 80 and over, Diabetic Nephropathies/blood, General Medicine, Middle Aged, Atrasentan/administration & dosage, Editorial Commentary, Treatment Outcome, Nephrology, Creatinine, Administration, young adult, Female, medicine.symptom, Glomerular filtration rate, Type 2, Endothelin A Receptor Antagonists/administration & dosage, medicine.drug, Glomerular Filtration Rate, Human, Oral, Adult, medicine.medical_specialty, ALBUMINURIA, Endothelin A Receptor Antagonists, NEPHROPATHY, Urology, INHIBITION, Renal function, Serum Albumin, Human, Placebo, Nephropathy, 03 medical and health sciences, Young Adult, Double-Blind Method, Atresentan, diabetes, chronic kidney disease, medicine, Diabetes Mellitus, Aged, Atrasentan, Diabetes Mellitus, Type 2, Humans, Renal Insufficiency, Chronic, Serum Albumin, business.industry, Creatinine/blood, medicine.disease, Serum Albumin, Human/urine, n/a OA procedure, chemistry, Albuminuria, Renal Insufficiency, Chronic/blood, business, aged, 80 and over, Kidney disease
Abstract

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Published
2019

4. [Usefulness and limitations of basal insulin replacement in type 2 diabetes]

Author

Erina, Hirata, Kazuno, Ohmori, and Sou, Nagai

Subjects
Insulin, Long-Acting, Diabetes Mellitus, Type 2, Insulin Detemir, Insulin, Isophane, Humans, Insulin Glargine
Abstract

In the earlier stage of type 2 diabetes, the disease can be managed by life-style modification with or without oral antidiabetic agents. However, as the disease progress, most patients eventually require insulin treatment to maintain good glycemic/control. Optimal insulin therapy should mimic the normal physiologic secretory pattern. As for ideal basal insulin, to maintain desirable pre-prandial glucose levels, duration of action should be long enough, profiles such as flat time-action and less day-to-day variation would be mandatory. This article discusses the usefulness and limitations of basal insulin therapy in type 2 diabetes comparing NPH insulin, insulin detemir, insulin glargin and insulin degludec.

Published
2015

5. Peripheral Pulmonary Embolism Related to a Thrombus of the Inferior Vena Cava Triggering Fatal Adrenal Crisis in Sheehan's Syndrome

Author

Sou Nagai, Chikara Shimizu, Akihiro Ishizu, Takahiro Tsuji, and Takashi Yoshiki

Subjects
medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Adrenal crisis, medicine.disease, Inferior vena cava, Pulmonary embolism, Peripheral, Endocrinology, medicine.vein, Internal medicine, medicine, Cardiology, Radiology, Sheehan's syndrome, medicine.symptom, Thrombus, business
Published
2004

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