Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease

Dick De Zeeuw, Tadao Akizawa, Paul Audhya, George L. Bakris, Melanie Chin, Heidi Christ-Schmidt, Angie Goldsberry, Mark Houser, Melissa Krauth, Hiddo J. Lambers Heerspink, John J. McMurray, Colin J. Meyer, Hans Henrik Parving, Giuseppe Remuzzi, Robert D. Toto, Nosratola D. Vaziri, Christoph Wanner, Janet Wittes, Danielle Wrolstad, Glenn M. Chertow & 334 others B. Toto, P. McCullough, P. Ivanovich, M. Ketteler, J. Lachin, J. McGill, R. Agarwal, S. Anker, J. F. Arenillas, J. Januzzi, A. Jardine, S. Kasner, B. Kissela, D. Kolansky, J. Mann, R. Thadhani, P. Champion de Crespigny, D. T. Chan, E. D'Almeida, I. Fraser, N. Gray, S. Holt, A. Irish, N. Isbel, P. Kerr, D. Packham, R. Phoon, C. Pollock, S. Roger, M. Suranyi, R. Walker, G. Wittert, D. Yue, P. Balcke, R. Prager, G. Schernthaner, G. Schernthaner, G. Sunder-Plassmann, M. Jadoul, J. M. Krzesinski, P. Peeters, P. Van der Niepen, L. Van Gaal, B. Van Vlem, X. Warling, S. Chow, S. Cournoyer, R. Dumas, S. Jolly, A. Levin, A. McMahon, H. Mehta, T. C. Ooi, D. Perkins, L. Roy, D. Sapir, P. Tam, D. Bartaskova, L. Hemzsky, D. Kubina, M. Szabo, V. Tesar, C. Combe, B. Faller, J. P. Fauvel, J. M. Halimi, M. Hourmant, Y. Le Meur, P. Urena-Torres, P. Zaoui, S. Al-Sarraf, V. Burst, S. Degenhardt, H. P. Kempe, W. Kleophas, C. Kosch, B. Krumme, M. Kuhlmann, F. Pistrosch, M. Rambausek, H. Schmidt-Guertler, T. Segiet, C. Sommerer, V. Vielhauer, C. Wanner, I. Beberashvili, S. Benchetrit, T. Herskovits, E. Karnieli, N. Levin-Iaina, O. Mosenzon, A. Tsur, D. J. van Dijk, J. Wainstein, Y. Yagil, Y. Yerushalmi, G. Colussi, G. Conte, M. Di Luca, C. Giovambatista, P. Messa, A. Pani, A. Pisani, M. R. Rapana, P. Ruggenenti, G. Villa, C. Zoccali, R. Correa-Rotter, S. L. Diaz-Escobedo, P. Garcia, G. Gonzalez Galvez, G. T. Obrador Vera, R. Rico, F. Calero, S. Cigarran, F. de Alvaro, A. L. de Francisco, J. Egido, E. Fernandez, F. Fernandez Vega, J. Fort, A. Galan Serrano, J. L. Gorriz Teruel, I. Martinez, A. Martinez Castelao, M. A. Munar, J. Navarro, J. Nieto, A. Osuna, J. Pascual, J. Portoles, M. Praga, M. Vallés, B. Fellstrom, C. Frisenette-Fich, H. Hadimeri, P. Stenvinkel, M. Svensson, L. Weiss, K. Adamson, A. Dornhorst, M. El Kossi, L. Gnudi, B. Hendry, A. Johnson, F. Joseph, P. Kalra, S. Marshall, A. Mikhail, K. S. Myint, H. Soran, M. Taal, D. Zehnder, L. Abbott, A. Acharya, Z. Ahmed, J. Aiello, M. Akom, S. Ali, O. Alzohaili, L. Anderson, S. Anderson, M. Anger, G. Appel, R. F. Arakaki, A. Arif, A. R. Assefi, N. Atray, A. Awad, E. Barranco, M. O. Belledonne, D. Belo, M. Bernardo, R. Bernstein, V. Bhalla, D. Bhatia, R. M. Black, G. Block, J. Blondin, S. S. Blumenthal, P. Bononi, R. R. Brantley, P. Bresssler, V. Broumand, O. Brusco, J. Buerkert, R. Burgos-Calderon, R. Campbell, G. Canas, J. Cangiano, R. Cherlin, V. Chilakapati, R. Comunale, D. Coyne, P. W. Crawford, R. Darwish, W. Deeb, P. S. Denker, S. Desai, C. Desouza, S. Diamond, B. S. Dixon, J. H. Durham, G. Eisner, J. G. Elder, M. El-Shahawy, G. Fadda, D. Fitz-Patrick, V. Fonseca, N. J. Fraser, G. Frei, L. Fried, E. Galindo-Ramos, M. Germain, W. Ghantous, J. M. Gilbert, D. Gillum, J. Godwin, A. Goel, DS Goldfarb, R. J. Graf, T. Greenwood, A. Guasch, A. Hanna, K. Harper, T. Herman, T. Hilton, T. Hines, J. Hoggard, R. Hootkins, R. Huseman, A. Israelit, A. Jamal, K. Kant, E. Kaptein, A. Kathresal, J. Kaupke, K. Kaveh, W. Kaye, G. E. Keightley, K. Keith, Q. Khairullah, V. Kondle, N. Kopyt, G. Krishna, M. K. Lawrence, M. LeBeau, D. J. Leehey, M. M. Levine, D. Levinson, S. Q. Lew, D. Lewis, D. Linfert, K. Liss, R. Lund, P. Madeleine, K. Mahmood, E. R. Martin, C. Martinez, S. O. Mayeda, R. Mendez, J. Middleton, M. E. Molitch, J. Moncrief, M. Moustafa, R. Muoneke, A. V. Murray, T. S. Murugan, T. M. Nammour, G. Nassar, S. Navaneethan, J. Newman, A. Nossuli, I. Nwakoby, S. Osama, R. Ouseph, J. Parker, E. Parnes, N. Patel, P. Pergola, A. Perlman, R. G. Perry, R. Petrillo, S. Prabhakar, R. S. Purighalla, L. Quesada-Suarez, A. Rabiei, P. Raskin, A. Rastogi, E. Reisin, A. Rekhi, L. Rivera-Colon, D. Rizk, R. Rodelas, D. Roer, S. Rosas, D. L. Ross, S. Rovner, H. Sackel, S. Sader, P. Santos, R. Schmidt, S. Shafik, M. Shakeel, Z. Sharon, A. L. Silva, A. Silva, B. Singh, M. Smith, R. Solomon, S. Soman, B. Spinowitz, S. M. Sprague, L. Spry, L. Stonesifer, D. Streja, P. Suchinda, C. Sun, C. V. Thakar, F. Trespalacios, J. A. Tumlin, P. Van Buren, M. Vernace, S. Vicks, M. Warren, D. Weiss, J. Welker, J. A. Winston, D. G. Wombolt, M. Wood, M. Wu, A. Wynne, H. Yu, R. I. Zabaneh

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Abstract

BACKGROUND: Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown. METHODS: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. RESULTS: The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. CONCLUSIONS: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial.

LanguageEnglish
Pages2492-2503
Number of pages12
JournalNew England Journal of Medicine
Volume369
Issue number26
DOIs
Publication statusPublished - 1 Jan 2013

ASJC Scopus subject areas

  • Medicine(all)

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De Zeeuw, D., Akizawa, T., Audhya, P., Bakris, G. L., Chin, M., Christ-Schmidt, H., ... Zabaneh, R. I. (2013). Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. New England Journal of Medicine, 369(26), 2492-2503. https://doi.org/10.1056/NEJMoa1306033
De Zeeuw, Dick ; Akizawa, Tadao ; Audhya, Paul ; Bakris, George L. ; Chin, Melanie ; Christ-Schmidt, Heidi ; Goldsberry, Angie ; Houser, Mark ; Krauth, Melissa ; Lambers Heerspink, Hiddo J. ; McMurray, John J. ; Meyer, Colin J. ; Parving, Hans Henrik ; Remuzzi, Giuseppe ; Toto, Robert D. ; Vaziri, Nosratola D. ; Wanner, Christoph ; Wittes, Janet ; Wrolstad, Danielle ; Chertow, Glenn M. ; Toto, B. ; McCullough, P. ; Ivanovich, P. ; Ketteler, M. ; Lachin, J. ; McGill, J. ; Agarwal, R. ; Anker, S. ; Arenillas, J. F. ; Januzzi, J. ; Jardine, A. ; Kasner, S. ; Kissela, B. ; Kolansky, D. ; Mann, J. ; Thadhani, R. ; Champion de Crespigny, P. ; Chan, D. T. ; D'Almeida, E. ; Fraser, I. ; Gray, N. ; Holt, S. ; Irish, A. ; Isbel, N. ; Kerr, P. ; Packham, D. ; Phoon, R. ; Pollock, C. ; Roger, S. ; Suranyi, M. ; Walker, R. ; Wittert, G. ; Yue, D. ; Balcke, P. ; Prager, R. ; Schernthaner, G. ; Schernthaner, G. ; Sunder-Plassmann, G. ; Jadoul, M. ; Krzesinski, J. M. ; Peeters, P. ; Van der Niepen, P. ; Van Gaal, L. ; Van Vlem, B. ; Warling, X. ; Chow, S. ; Cournoyer, S. ; Dumas, R. ; Jolly, S. ; Levin, A. ; McMahon, A. ; Mehta, H. ; Ooi, T. C. ; Perkins, D. ; Roy, L. ; Sapir, D. ; Tam, P. ; Bartaskova, D. ; Hemzsky, L. ; Kubina, D. ; Szabo, M. ; Tesar, V. ; Combe, C. ; Faller, B. ; Fauvel, J. P. ; Halimi, J. M. ; Hourmant, M. ; Le Meur, Y. ; Urena-Torres, P. ; Zaoui, P. ; Al-Sarraf, S. ; Burst, V. ; Degenhardt, S. ; Kempe, H. P. ; Kleophas, W. ; Kosch, C. ; Krumme, B. ; Kuhlmann, M. ; Pistrosch, F. ; Rambausek, M. ; Schmidt-Guertler, H. ; Segiet, T. ; Sommerer, C. ; Vielhauer, V. ; Wanner, C. ; Beberashvili, I. ; Benchetrit, S. ; Herskovits, T. ; Karnieli, E. ; Levin-Iaina, N. ; Mosenzon, O. ; Tsur, A. ; van Dijk, D. J. ; Wainstein, J. ; Yagil, Y. ; Yerushalmi, Y. ; Colussi, G. ; Conte, G. ; Di Luca, M. ; Giovambatista, C. ; Messa, P. ; Pani, A. ; Pisani, A. ; Rapana, M. R. ; Ruggenenti, P. ; Villa, G. ; Zoccali, C. ; Correa-Rotter, R. ; Diaz-Escobedo, S. L. ; Garcia, P. ; Gonzalez Galvez, G. ; Obrador Vera, G. T. ; Rico, R. ; Calero, F. ; Cigarran, S. ; de Alvaro, F. ; de Francisco, A. L. ; Egido, J. ; Fernandez, E. ; Fernandez Vega, F. ; Fort, J. ; Galan Serrano, A. ; Gorriz Teruel, J. L. ; Martinez, I. ; Martinez Castelao, A. ; Munar, M. A. ; Navarro, J. ; Nieto, J. ; Osuna, A. ; Pascual, J. ; Portoles, J. ; Praga, M. ; Vallés, M. ; Fellstrom, B. ; Frisenette-Fich, C. ; Hadimeri, H. ; Stenvinkel, P. ; Svensson, M. ; Weiss, L. ; Adamson, K. ; Dornhorst, A. ; El Kossi, M. ; Gnudi, L. ; Hendry, B. ; Johnson, A. ; Joseph, F. ; Kalra, P. ; Marshall, S. ; Mikhail, A. ; Myint, K. S. ; Soran, H. ; Taal, M. ; Zehnder, D. ; Abbott, L. ; Acharya, A. ; Ahmed, Z. ; Aiello, J. ; Akom, M. ; Ali, S. ; Alzohaili, O. ; Anderson, L. ; Anderson, S. ; Anger, M. ; Appel, G. ; Arakaki, R. F. ; Arif, A. ; Assefi, A. R. ; Atray, N. ; Awad, A. ; Barranco, E. ; Belledonne, M. O. ; Belo, D. ; Bernardo, M. ; Bernstein, R. ; Bhalla, V. ; Bhatia, D. ; Black, R. M. ; Block, G. ; Blondin, J. ; Blumenthal, S. S. ; Bononi, P. ; Brantley, R. R. ; Bresssler, P. ; Broumand, V. ; Brusco, O. ; Buerkert, J. ; Burgos-Calderon, R. ; Campbell, R. ; Canas, G. ; Cangiano, J. ; Cherlin, R. ; Chilakapati, V. ; Comunale, R. ; Coyne, D. ; Crawford, P. W. ; Darwish, R. ; Deeb, W. ; Denker, P. S. ; Desai, S. ; Desouza, C. ; Diamond, S. ; Dixon, B. S. ; Durham, J. H. ; Eisner, G. ; Elder, J. G. ; El-Shahawy, M. ; Fadda, G. ; Fitz-Patrick, D. ; Fonseca, V. ; Fraser, N. J. ; Frei, G. ; Fried, L. ; Galindo-Ramos, E. ; Germain, M. ; Ghantous, W. ; Gilbert, J. M. ; Gillum, D. ; Godwin, J. ; Goel, A. ; Goldfarb, DS ; Graf, R. J. ; Greenwood, T. ; Guasch, A. ; Hanna, A. ; Harper, K. ; Herman, T. ; Hilton, T. ; Hines, T. ; Hoggard, J. ; Hootkins, R. ; Huseman, R. ; Israelit, A. ; Jamal, A. ; Kant, K. ; Kaptein, E. ; Kathresal, A. ; Kaupke, J. ; Kaveh, K. ; Kaye, W. ; Keightley, G. E. ; Keith, K. ; Khairullah, Q. ; Kondle, V. ; Kopyt, N. ; Krishna, G. ; Lawrence, M. K. ; LeBeau, M. ; Leehey, D. J. ; Levine, M. M. ; Levinson, D. ; Lew, S. Q. ; Lewis, D. ; Linfert, D. ; Liss, K. ; Lund, R. ; Madeleine, P. ; Mahmood, K. ; Martin, E. R. ; Martinez, C. ; Mayeda, S. O. ; Mendez, R. ; Middleton, J. ; Molitch, M. E. ; Moncrief, J. ; Moustafa, M. ; Muoneke, R. ; Murray, A. V. ; Murugan, T. S. ; Nammour, T. M. ; Nassar, G. ; Navaneethan, S. ; Newman, J. ; Nossuli, A. ; Nwakoby, I. ; Osama, S. ; Ouseph, R. ; Parker, J. ; Parnes, E. ; Patel, N. ; Pergola, P. ; Perlman, A. ; Perry, R. G. ; Petrillo, R. ; Prabhakar, S. ; Purighalla, R. S. ; Quesada-Suarez, L. ; Rabiei, A. ; Raskin, P. ; Rastogi, A. ; Reisin, E. ; Rekhi, A. ; Rivera-Colon, L. ; Rizk, D. ; Rodelas, R. ; Roer, D. ; Rosas, S. ; Ross, D. L. ; Rovner, S. ; Sackel, H. ; Sader, S. ; Santos, P. ; Schmidt, R. ; Shafik, S. ; Shakeel, M. ; Sharon, Z. ; Silva, A. L. ; Silva, A. ; Singh, B. ; Smith, M. ; Solomon, R. ; Soman, S. ; Spinowitz, B. ; Sprague, S. M. ; Spry, L. ; Stonesifer, L. ; Streja, D. ; Suchinda, P. ; Sun, C. ; Thakar, C. V. ; Trespalacios, F. ; Tumlin, J. A. ; Van Buren, P. ; Vernace, M. ; Vicks, S. ; Warren, M. ; Weiss, D. ; Welker, J. ; Winston, J. A. ; Wombolt, D. G. ; Wood, M. ; Wu, M. ; Wynne, A. ; Yu, H. ; Zabaneh, R. I. / Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 26. pp. 2492-2503.
@article{1028b683d5c14a449309ac0f43061617,
title = "Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease",
abstract = "BACKGROUND: Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown. METHODS: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. RESULTS: The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6{\%}) randomly assigned to bardoxolone methyl and 69 of 1097 (6{\%}) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95{\%} confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95{\%} CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. CONCLUSIONS: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial.",
author = "{De Zeeuw}, Dick and Tadao Akizawa and Paul Audhya and Bakris, {George L.} and Melanie Chin and Heidi Christ-Schmidt and Angie Goldsberry and Mark Houser and Melissa Krauth and {Lambers Heerspink}, {Hiddo J.} and McMurray, {John J.} and Meyer, {Colin J.} and Parving, {Hans Henrik} and Giuseppe Remuzzi and Toto, {Robert D.} and Vaziri, {Nosratola D.} and Christoph Wanner and Janet Wittes and Danielle Wrolstad and Chertow, {Glenn M.} and B. Toto and P. McCullough and P. Ivanovich and M. Ketteler and J. Lachin and J. McGill and R. Agarwal and S. Anker and Arenillas, {J. F.} and J. Januzzi and A. Jardine and S. Kasner and B. Kissela and D. Kolansky and J. Mann and R. Thadhani and {Champion de Crespigny}, P. and Chan, {D. T.} and E. D'Almeida and I. Fraser and N. Gray and S. Holt and A. Irish and N. Isbel and P. Kerr and D. Packham and R. Phoon and C. Pollock and S. Roger and M. Suranyi and R. Walker and G. Wittert and D. Yue and P. Balcke and R. Prager and G. Schernthaner and G. Schernthaner and G. Sunder-Plassmann and M. Jadoul and Krzesinski, {J. M.} and P. Peeters and {Van der Niepen}, P. and {Van Gaal}, L. and {Van Vlem}, B. and X. Warling and S. Chow and S. Cournoyer and R. Dumas and S. Jolly and A. Levin and A. McMahon and H. Mehta and Ooi, {T. C.} and D. Perkins and L. Roy and D. Sapir and P. Tam and D. Bartaskova and L. Hemzsky and D. Kubina and M. Szabo and V. Tesar and C. Combe and B. Faller and Fauvel, {J. P.} and Halimi, {J. M.} and M. Hourmant and {Le Meur}, Y. and P. Urena-Torres and P. Zaoui and S. Al-Sarraf and V. Burst and S. Degenhardt and Kempe, {H. P.} and W. Kleophas and C. Kosch and B. Krumme and M. Kuhlmann and F. Pistrosch and M. Rambausek and H. Schmidt-Guertler and T. Segiet and C. Sommerer and V. Vielhauer and C. Wanner and I. Beberashvili and S. Benchetrit and T. Herskovits and E. Karnieli and N. Levin-Iaina and O. Mosenzon and A. Tsur and {van Dijk}, {D. J.} and J. Wainstein and Y. Yagil and Y. Yerushalmi and G. Colussi and G. Conte and {Di Luca}, M. and C. Giovambatista and P. Messa and A. Pani and A. Pisani and Rapana, {M. R.} and P. Ruggenenti and G. Villa and C. Zoccali and R. Correa-Rotter and Diaz-Escobedo, {S. L.} and P. Garcia and {Gonzalez Galvez}, G. and {Obrador Vera}, {G. T.} and R. Rico and F. Calero and S. Cigarran and {de Alvaro}, F. and {de Francisco}, {A. L.} and J. Egido and E. Fernandez and {Fernandez Vega}, F. and J. Fort and {Galan Serrano}, A. and {Gorriz Teruel}, {J. L.} and I. Martinez and {Martinez Castelao}, A. and Munar, {M. A.} and J. Navarro and J. Nieto and A. Osuna and J. Pascual and J. Portoles and M. Praga and M. Vall{\'e}s and B. Fellstrom and C. Frisenette-Fich and H. Hadimeri and P. Stenvinkel and M. Svensson and L. Weiss and K. Adamson and A. Dornhorst and {El Kossi}, M. and L. Gnudi and B. Hendry and A. Johnson and F. Joseph and P. Kalra and S. Marshall and A. Mikhail and Myint, {K. S.} and H. Soran and M. Taal and D. Zehnder and L. Abbott and A. Acharya and Z. Ahmed and J. Aiello and M. Akom and S. Ali and O. Alzohaili and L. Anderson and S. Anderson and M. Anger and G. Appel and Arakaki, {R. F.} and A. Arif and Assefi, {A. R.} and N. Atray and A. Awad and E. Barranco and Belledonne, {M. O.} and D. Belo and M. Bernardo and R. Bernstein and V. Bhalla and D. Bhatia and Black, {R. M.} and G. Block and J. Blondin and Blumenthal, {S. S.} and P. Bononi and Brantley, {R. R.} and P. Bresssler and V. Broumand and O. Brusco and J. Buerkert and R. Burgos-Calderon and R. Campbell and G. Canas and J. Cangiano and R. Cherlin and V. Chilakapati and R. Comunale and D. Coyne and Crawford, {P. W.} and R. Darwish and W. Deeb and Denker, {P. S.} and S. Desai and C. Desouza and S. Diamond and Dixon, {B. S.} and Durham, {J. H.} and G. Eisner and Elder, {J. G.} and M. El-Shahawy and G. Fadda and D. Fitz-Patrick and V. Fonseca and Fraser, {N. J.} and G. Frei and L. Fried and E. Galindo-Ramos and M. Germain and W. Ghantous and Gilbert, {J. M.} and D. Gillum and J. Godwin and A. Goel and DS Goldfarb and Graf, {R. J.} and T. Greenwood and A. Guasch and A. Hanna and K. Harper and T. Herman and T. Hilton and T. Hines and J. Hoggard and R. Hootkins and R. Huseman and A. Israelit and A. Jamal and K. Kant and E. Kaptein and A. Kathresal and J. Kaupke and K. Kaveh and W. Kaye and Keightley, {G. E.} and K. Keith and Q. Khairullah and V. Kondle and N. Kopyt and G. Krishna and Lawrence, {M. K.} and M. LeBeau and Leehey, {D. J.} and Levine, {M. M.} and D. Levinson and Lew, {S. Q.} and D. Lewis and D. Linfert and K. Liss and R. Lund and P. Madeleine and K. Mahmood and Martin, {E. R.} and C. Martinez and Mayeda, {S. O.} and R. Mendez and J. Middleton and Molitch, {M. E.} and J. Moncrief and M. Moustafa and R. Muoneke and Murray, {A. V.} and Murugan, {T. S.} and Nammour, {T. M.} and G. Nassar and S. Navaneethan and J. Newman and A. Nossuli and I. Nwakoby and S. Osama and R. Ouseph and J. Parker and E. Parnes and N. Patel and P. Pergola and A. Perlman and Perry, {R. G.} and R. Petrillo and S. Prabhakar and Purighalla, {R. S.} and L. Quesada-Suarez and A. Rabiei and P. Raskin and A. Rastogi and E. Reisin and A. Rekhi and L. Rivera-Colon and D. Rizk and R. Rodelas and D. Roer and S. Rosas and Ross, {D. L.} and S. Rovner and H. Sackel and S. Sader and P. Santos and R. Schmidt and S. Shafik and M. Shakeel and Z. Sharon and Silva, {A. L.} and A. Silva and B. Singh and M. Smith and R. Solomon and S. Soman and B. Spinowitz and Sprague, {S. M.} and L. Spry and L. Stonesifer and D. Streja and P. Suchinda and C. Sun and Thakar, {C. V.} and F. Trespalacios and Tumlin, {J. A.} and {Van Buren}, P. and M. Vernace and S. Vicks and M. Warren and D. Weiss and J. Welker and Winston, {J. A.} and Wombolt, {D. G.} and M. Wood and M. Wu and A. Wynne and H. Yu and Zabaneh, {R. I.}",
year = "2013",
month = "1",
day = "1",
doi = "10.1056/NEJMoa1306033",
language = "English",
volume = "369",
pages = "2492--2503",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "26",

}

De Zeeuw, D, Akizawa, T, Audhya, P, Bakris, GL, Chin, M, Christ-Schmidt, H, Goldsberry, A, Houser, M, Krauth, M, Lambers Heerspink, HJ, McMurray, JJ, Meyer, CJ, Parving, HH, Remuzzi, G, Toto, RD, Vaziri, ND, Wanner, C, Wittes, J, Wrolstad, D, Chertow, GM, Toto, B, McCullough, P, Ivanovich, P, Ketteler, M, Lachin, J, McGill, J, Agarwal, R, Anker, S, Arenillas, JF, Januzzi, J, Jardine, A, Kasner, S, Kissela, B, Kolansky, D, Mann, J, Thadhani, R, Champion de Crespigny, P, Chan, DT, D'Almeida, E, Fraser, I, Gray, N, Holt, S, Irish, A, Isbel, N, Kerr, P, Packham, D, Phoon, R, Pollock, C, Roger, S, Suranyi, M, Walker, R, Wittert, G, Yue, D, Balcke, P, Prager, R, Schernthaner, G, Schernthaner, G, Sunder-Plassmann, G, Jadoul, M, Krzesinski, JM, Peeters, P, Van der Niepen, P, Van Gaal, L, Van Vlem, B, Warling, X, Chow, S, Cournoyer, S, Dumas, R, Jolly, S, Levin, A, McMahon, A, Mehta, H, Ooi, TC, Perkins, D, Roy, L, Sapir, D, Tam, P, Bartaskova, D, Hemzsky, L, Kubina, D, Szabo, M, Tesar, V, Combe, C, Faller, B, Fauvel, JP, Halimi, JM, Hourmant, M, Le Meur, Y, Urena-Torres, P, Zaoui, P, Al-Sarraf, S, Burst, V, Degenhardt, S, Kempe, HP, Kleophas, W, Kosch, C, Krumme, B, Kuhlmann, M, Pistrosch, F, Rambausek, M, Schmidt-Guertler, H, Segiet, T, Sommerer, C, Vielhauer, V, Wanner, C, Beberashvili, I, Benchetrit, S, Herskovits, T, Karnieli, E, Levin-Iaina, N, Mosenzon, O, Tsur, A, van Dijk, DJ, Wainstein, J, Yagil, Y, Yerushalmi, Y, Colussi, G, Conte, G, Di Luca, M, Giovambatista, C, Messa, P, Pani, A, Pisani, A, Rapana, MR, Ruggenenti, P, Villa, G, Zoccali, C, Correa-Rotter, R, Diaz-Escobedo, SL, Garcia, P, Gonzalez Galvez, G, Obrador Vera, GT, Rico, R, Calero, F, Cigarran, S, de Alvaro, F, de Francisco, AL, Egido, J, Fernandez, E, Fernandez Vega, F, Fort, J, Galan Serrano, A, Gorriz Teruel, JL, Martinez, I, Martinez Castelao, A, Munar, MA, Navarro, J, Nieto, J, Osuna, A, Pascual, J, Portoles, J, Praga, M, Vallés, M, Fellstrom, B, Frisenette-Fich, C, Hadimeri, H, Stenvinkel, P, Svensson, M, Weiss, L, Adamson, K, Dornhorst, A, El Kossi, M, Gnudi, L, Hendry, B, Johnson, A, Joseph, F, Kalra, P, Marshall, S, Mikhail, A, Myint, KS, Soran, H, Taal, M, Zehnder, D, Abbott, L, Acharya, A, Ahmed, Z, Aiello, J, Akom, M, Ali, S, Alzohaili, O, Anderson, L, Anderson, S, Anger, M, Appel, G, Arakaki, RF, Arif, A, Assefi, AR, Atray, N, Awad, A, Barranco, E, Belledonne, MO, Belo, D, Bernardo, M, Bernstein, R, Bhalla, V, Bhatia, D, Black, RM, Block, G, Blondin, J, Blumenthal, SS, Bononi, P, Brantley, RR, Bresssler, P, Broumand, V, Brusco, O, Buerkert, J, Burgos-Calderon, R, Campbell, R, Canas, G, Cangiano, J, Cherlin, R, Chilakapati, V, Comunale, R, Coyne, D, Crawford, PW, Darwish, R, Deeb, W, Denker, PS, Desai, S, Desouza, C, Diamond, S, Dixon, BS, Durham, JH, Eisner, G, Elder, JG, El-Shahawy, M, Fadda, G, Fitz-Patrick, D, Fonseca, V, Fraser, NJ, Frei, G, Fried, L, Galindo-Ramos, E, Germain, M, Ghantous, W, Gilbert, JM, Gillum, D, Godwin, J, Goel, A, Goldfarb, DS, Graf, RJ, Greenwood, T, Guasch, A, Hanna, A, Harper, K, Herman, T, Hilton, T, Hines, T, Hoggard, J, Hootkins, R, Huseman, R, Israelit, A, Jamal, A, Kant, K, Kaptein, E, Kathresal, A, Kaupke, J, Kaveh, K, Kaye, W, Keightley, GE, Keith, K, Khairullah, Q, Kondle, V, Kopyt, N, Krishna, G, Lawrence, MK, LeBeau, M, Leehey, DJ, Levine, MM, Levinson, D, Lew, SQ, Lewis, D, Linfert, D, Liss, K, Lund, R, Madeleine, P, Mahmood, K, Martin, ER, Martinez, C, Mayeda, SO, Mendez, R, Middleton, J, Molitch, ME, Moncrief, J, Moustafa, M, Muoneke, R, Murray, AV, Murugan, TS, Nammour, TM, Nassar, G, Navaneethan, S, Newman, J, Nossuli, A, Nwakoby, I, Osama, S, Ouseph, R, Parker, J, Parnes, E, Patel, N, Pergola, P, Perlman, A, Perry, RG, Petrillo, R, Prabhakar, S, Purighalla, RS, Quesada-Suarez, L, Rabiei, A, Raskin, P, Rastogi, A, Reisin, E, Rekhi, A, Rivera-Colon, L, Rizk, D, Rodelas, R, Roer, D, Rosas, S, Ross, DL, Rovner, S, Sackel, H, Sader, S, Santos, P, Schmidt, R, Shafik, S, Shakeel, M, Sharon, Z, Silva, AL, Silva, A, Singh, B, Smith, M, Solomon, R, Soman, S, Spinowitz, B, Sprague, SM, Spry, L, Stonesifer, L, Streja, D, Suchinda, P, Sun, C, Thakar, CV, Trespalacios, F, Tumlin, JA, Van Buren, P, Vernace, M, Vicks, S, Warren, M, Weiss, D, Welker, J, Winston, JA, Wombolt, DG, Wood, M, Wu, M, Wynne, A, Yu, H & Zabaneh, RI 2013, 'Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease', New England Journal of Medicine, vol. 369, no. 26, pp. 2492-2503. https://doi.org/10.1056/NEJMoa1306033

Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. / De Zeeuw, Dick; Akizawa, Tadao; Audhya, Paul; Bakris, George L.; Chin, Melanie; Christ-Schmidt, Heidi; Goldsberry, Angie; Houser, Mark; Krauth, Melissa; Lambers Heerspink, Hiddo J.; McMurray, John J.; Meyer, Colin J.; Parving, Hans Henrik; Remuzzi, Giuseppe; Toto, Robert D.; Vaziri, Nosratola D.; Wanner, Christoph; Wittes, Janet; Wrolstad, Danielle; Chertow, Glenn M.; Toto, B.; McCullough, P.; Ivanovich, P.; Ketteler, M.; Lachin, J.; McGill, J.; Agarwal, R.; Anker, S.; Arenillas, J. F.; Januzzi, J.; Jardine, A.; Kasner, S.; Kissela, B.; Kolansky, D.; Mann, J.; Thadhani, R.; Champion de Crespigny, P.; Chan, D. T.; D'Almeida, E.; Fraser, I.; Gray, N.; Holt, S.; Irish, A.; Isbel, N.; Kerr, P.; Packham, D.; Phoon, R.; Pollock, C.; Roger, S.; Suranyi, M.; Walker, R.; Wittert, G.; Yue, D.; Balcke, P.; Prager, R.; Schernthaner, G.; Schernthaner, G.; Sunder-Plassmann, G.; Jadoul, M.; Krzesinski, J. M.; Peeters, P.; Van der Niepen, P.; Van Gaal, L.; Van Vlem, B.; Warling, X.; Chow, S.; Cournoyer, S.; Dumas, R.; Jolly, S.; Levin, A.; McMahon, A.; Mehta, H.; Ooi, T. C.; Perkins, D.; Roy, L.; Sapir, D.; Tam, P.; Bartaskova, D.; Hemzsky, L.; Kubina, D.; Szabo, M.; Tesar, V.; Combe, C.; Faller, B.; Fauvel, J. P.; Halimi, J. M.; Hourmant, M.; Le Meur, Y.; Urena-Torres, P.; Zaoui, P.; Al-Sarraf, S.; Burst, V.; Degenhardt, S.; Kempe, H. P.; Kleophas, W.; Kosch, C.; Krumme, B.; Kuhlmann, M.; Pistrosch, F.; Rambausek, M.; Schmidt-Guertler, H.; Segiet, T.; Sommerer, C.; Vielhauer, V.; Wanner, C.; Beberashvili, I.; Benchetrit, S.; Herskovits, T.; Karnieli, E.; Levin-Iaina, N.; Mosenzon, O.; Tsur, A.; van Dijk, D. J.; Wainstein, J.; Yagil, Y.; Yerushalmi, Y.; Colussi, G.; Conte, G.; Di Luca, M.; Giovambatista, C.; Messa, P.; Pani, A.; Pisani, A.; Rapana, M. R.; Ruggenenti, P.; Villa, G.; Zoccali, C.; Correa-Rotter, R.; Diaz-Escobedo, S. L.; Garcia, P.; Gonzalez Galvez, G.; Obrador Vera, G. T.; Rico, R.; Calero, F.; Cigarran, S.; de Alvaro, F.; de Francisco, A. L.; Egido, J.; Fernandez, E.; Fernandez Vega, F.; Fort, J.; Galan Serrano, A.; Gorriz Teruel, J. L.; Martinez, I.; Martinez Castelao, A.; Munar, M. A.; Navarro, J.; Nieto, J.; Osuna, A.; Pascual, J.; Portoles, J.; Praga, M.; Vallés, M.; Fellstrom, B.; Frisenette-Fich, C.; Hadimeri, H.; Stenvinkel, P.; Svensson, M.; Weiss, L.; Adamson, K.; Dornhorst, A.; El Kossi, M.; Gnudi, L.; Hendry, B.; Johnson, A.; Joseph, F.; Kalra, P.; Marshall, S.; Mikhail, A.; Myint, K. S.; Soran, H.; Taal, M.; Zehnder, D.; Abbott, L.; Acharya, A.; Ahmed, Z.; Aiello, J.; Akom, M.; Ali, S.; Alzohaili, O.; Anderson, L.; Anderson, S.; Anger, M.; Appel, G.; Arakaki, R. F.; Arif, A.; Assefi, A. R.; Atray, N.; Awad, A.; Barranco, E.; Belledonne, M. O.; Belo, D.; Bernardo, M.; Bernstein, R.; Bhalla, V.; Bhatia, D.; Black, R. M.; Block, G.; Blondin, J.; Blumenthal, S. S.; Bononi, P.; Brantley, R. R.; Bresssler, P.; Broumand, V.; Brusco, O.; Buerkert, J.; Burgos-Calderon, R.; Campbell, R.; Canas, G.; Cangiano, J.; Cherlin, R.; Chilakapati, V.; Comunale, R.; Coyne, D.; Crawford, P. W.; Darwish, R.; Deeb, W.; Denker, P. S.; Desai, S.; Desouza, C.; Diamond, S.; Dixon, B. S.; Durham, J. H.; Eisner, G.; Elder, J. G.; El-Shahawy, M.; Fadda, G.; Fitz-Patrick, D.; Fonseca, V.; Fraser, N. J.; Frei, G.; Fried, L.; Galindo-Ramos, E.; Germain, M.; Ghantous, W.; Gilbert, J. M.; Gillum, D.; Godwin, J.; Goel, A.; Goldfarb, DS; Graf, R. J.; Greenwood, T.; Guasch, A.; Hanna, A.; Harper, K.; Herman, T.; Hilton, T.; Hines, T.; Hoggard, J.; Hootkins, R.; Huseman, R.; Israelit, A.; Jamal, A.; Kant, K.; Kaptein, E.; Kathresal, A.; Kaupke, J.; Kaveh, K.; Kaye, W.; Keightley, G. E.; Keith, K.; Khairullah, Q.; Kondle, V.; Kopyt, N.; Krishna, G.; Lawrence, M. K.; LeBeau, M.; Leehey, D. J.; Levine, M. M.; Levinson, D.; Lew, S. Q.; Lewis, D.; Linfert, D.; Liss, K.; Lund, R.; Madeleine, P.; Mahmood, K.; Martin, E. R.; Martinez, C.; Mayeda, S. O.; Mendez, R.; Middleton, J.; Molitch, M. E.; Moncrief, J.; Moustafa, M.; Muoneke, R.; Murray, A. V.; Murugan, T. S.; Nammour, T. M.; Nassar, G.; Navaneethan, S.; Newman, J.; Nossuli, A.; Nwakoby, I.; Osama, S.; Ouseph, R.; Parker, J.; Parnes, E.; Patel, N.; Pergola, P.; Perlman, A.; Perry, R. G.; Petrillo, R.; Prabhakar, S.; Purighalla, R. S.; Quesada-Suarez, L.; Rabiei, A.; Raskin, P.; Rastogi, A.; Reisin, E.; Rekhi, A.; Rivera-Colon, L.; Rizk, D.; Rodelas, R.; Roer, D.; Rosas, S.; Ross, D. L.; Rovner, S.; Sackel, H.; Sader, S.; Santos, P.; Schmidt, R.; Shafik, S.; Shakeel, M.; Sharon, Z.; Silva, A. L.; Silva, A.; Singh, B.; Smith, M.; Solomon, R.; Soman, S.; Spinowitz, B.; Sprague, S. M.; Spry, L.; Stonesifer, L.; Streja, D.; Suchinda, P.; Sun, C.; Thakar, C. V.; Trespalacios, F.; Tumlin, J. A.; Van Buren, P.; Vernace, M.; Vicks, S.; Warren, M.; Weiss, D.; Welker, J.; Winston, J. A.; Wombolt, D. G.; Wood, M.; Wu, M.; Wynne, A.; Yu, H.; Zabaneh, R. I.

In: New England Journal of Medicine, Vol. 369, No. 26, 01.01.2013, p. 2492-2503.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease

AU - De Zeeuw, Dick

AU - Akizawa, Tadao

AU - Audhya, Paul

AU - Bakris, George L.

AU - Chin, Melanie

AU - Christ-Schmidt, Heidi

AU - Goldsberry, Angie

AU - Houser, Mark

AU - Krauth, Melissa

AU - Lambers Heerspink, Hiddo J.

AU - McMurray, John J.

AU - Meyer, Colin J.

AU - Parving, Hans Henrik

AU - Remuzzi, Giuseppe

AU - Toto, Robert D.

AU - Vaziri, Nosratola D.

AU - Wanner, Christoph

AU - Wittes, Janet

AU - Wrolstad, Danielle

AU - Chertow, Glenn M.

AU - Toto, B.

AU - McCullough, P.

AU - Ivanovich, P.

AU - Ketteler, M.

AU - Lachin, J.

AU - McGill, J.

AU - Agarwal, R.

AU - Anker, S.

AU - Arenillas, J. F.

AU - Januzzi, J.

AU - Jardine, A.

AU - Kasner, S.

AU - Kissela, B.

AU - Kolansky, D.

AU - Mann, J.

AU - Thadhani, R.

AU - Champion de Crespigny, P.

AU - Chan, D. T.

AU - D'Almeida, E.

AU - Fraser, I.

AU - Gray, N.

AU - Holt, S.

AU - Irish, A.

AU - Isbel, N.

AU - Kerr, P.

AU - Packham, D.

AU - Phoon, R.

AU - Pollock, C.

AU - Roger, S.

AU - Suranyi, M.

AU - Walker, R.

AU - Wittert, G.

AU - Yue, D.

AU - Balcke, P.

AU - Prager, R.

AU - Schernthaner, G.

AU - Schernthaner, G.

AU - Sunder-Plassmann, G.

AU - Jadoul, M.

AU - Krzesinski, J. M.

AU - Peeters, P.

AU - Van der Niepen, P.

AU - Van Gaal, L.

AU - Van Vlem, B.

AU - Warling, X.

AU - Chow, S.

AU - Cournoyer, S.

AU - Dumas, R.

AU - Jolly, S.

AU - Levin, A.

AU - McMahon, A.

AU - Mehta, H.

AU - Ooi, T. C.

AU - Perkins, D.

AU - Roy, L.

AU - Sapir, D.

AU - Tam, P.

AU - Bartaskova, D.

AU - Hemzsky, L.

AU - Kubina, D.

AU - Szabo, M.

AU - Tesar, V.

AU - Combe, C.

AU - Faller, B.

AU - Fauvel, J. P.

AU - Halimi, J. M.

AU - Hourmant, M.

AU - Le Meur, Y.

AU - Urena-Torres, P.

AU - Zaoui, P.

AU - Al-Sarraf, S.

AU - Burst, V.

AU - Degenhardt, S.

AU - Kempe, H. P.

AU - Kleophas, W.

AU - Kosch, C.

AU - Krumme, B.

AU - Kuhlmann, M.

AU - Pistrosch, F.

AU - Rambausek, M.

AU - Schmidt-Guertler, H.

AU - Segiet, T.

AU - Sommerer, C.

AU - Vielhauer, V.

AU - Wanner, C.

AU - Beberashvili, I.

AU - Benchetrit, S.

AU - Herskovits, T.

AU - Karnieli, E.

AU - Levin-Iaina, N.

AU - Mosenzon, O.

AU - Tsur, A.

AU - van Dijk, D. J.

AU - Wainstein, J.

AU - Yagil, Y.

AU - Yerushalmi, Y.

AU - Colussi, G.

AU - Conte, G.

AU - Di Luca, M.

AU - Giovambatista, C.

AU - Messa, P.

AU - Pani, A.

AU - Pisani, A.

AU - Rapana, M. R.

AU - Ruggenenti, P.

AU - Villa, G.

AU - Zoccali, C.

AU - Correa-Rotter, R.

AU - Diaz-Escobedo, S. L.

AU - Garcia, P.

AU - Gonzalez Galvez, G.

AU - Obrador Vera, G. T.

AU - Rico, R.

AU - Calero, F.

AU - Cigarran, S.

AU - de Alvaro, F.

AU - de Francisco, A. L.

AU - Egido, J.

AU - Fernandez, E.

AU - Fernandez Vega, F.

AU - Fort, J.

AU - Galan Serrano, A.

AU - Gorriz Teruel, J. L.

AU - Martinez, I.

AU - Martinez Castelao, A.

AU - Munar, M. A.

AU - Navarro, J.

AU - Nieto, J.

AU - Osuna, A.

AU - Pascual, J.

AU - Portoles, J.

AU - Praga, M.

AU - Vallés, M.

AU - Fellstrom, B.

AU - Frisenette-Fich, C.

AU - Hadimeri, H.

AU - Stenvinkel, P.

AU - Svensson, M.

AU - Weiss, L.

AU - Adamson, K.

AU - Dornhorst, A.

AU - El Kossi, M.

AU - Gnudi, L.

AU - Hendry, B.

AU - Johnson, A.

AU - Joseph, F.

AU - Kalra, P.

AU - Marshall, S.

AU - Mikhail, A.

AU - Myint, K. S.

AU - Soran, H.

AU - Taal, M.

AU - Zehnder, D.

AU - Abbott, L.

AU - Acharya, A.

AU - Ahmed, Z.

AU - Aiello, J.

AU - Akom, M.

AU - Ali, S.

AU - Alzohaili, O.

AU - Anderson, L.

AU - Anderson, S.

AU - Anger, M.

AU - Appel, G.

AU - Arakaki, R. F.

AU - Arif, A.

AU - Assefi, A. R.

AU - Atray, N.

AU - Awad, A.

AU - Barranco, E.

AU - Belledonne, M. O.

AU - Belo, D.

AU - Bernardo, M.

AU - Bernstein, R.

AU - Bhalla, V.

AU - Bhatia, D.

AU - Black, R. M.

AU - Block, G.

AU - Blondin, J.

AU - Blumenthal, S. S.

AU - Bononi, P.

AU - Brantley, R. R.

AU - Bresssler, P.

AU - Broumand, V.

AU - Brusco, O.

AU - Buerkert, J.

AU - Burgos-Calderon, R.

AU - Campbell, R.

AU - Canas, G.

AU - Cangiano, J.

AU - Cherlin, R.

AU - Chilakapati, V.

AU - Comunale, R.

AU - Coyne, D.

AU - Crawford, P. W.

AU - Darwish, R.

AU - Deeb, W.

AU - Denker, P. S.

AU - Desai, S.

AU - Desouza, C.

AU - Diamond, S.

AU - Dixon, B. S.

AU - Durham, J. H.

AU - Eisner, G.

AU - Elder, J. G.

AU - El-Shahawy, M.

AU - Fadda, G.

AU - Fitz-Patrick, D.

AU - Fonseca, V.

AU - Fraser, N. J.

AU - Frei, G.

AU - Fried, L.

AU - Galindo-Ramos, E.

AU - Germain, M.

AU - Ghantous, W.

AU - Gilbert, J. M.

AU - Gillum, D.

AU - Godwin, J.

AU - Goel, A.

AU - Goldfarb, DS

AU - Graf, R. J.

AU - Greenwood, T.

AU - Guasch, A.

AU - Hanna, A.

AU - Harper, K.

AU - Herman, T.

AU - Hilton, T.

AU - Hines, T.

AU - Hoggard, J.

AU - Hootkins, R.

AU - Huseman, R.

AU - Israelit, A.

AU - Jamal, A.

AU - Kant, K.

AU - Kaptein, E.

AU - Kathresal, A.

AU - Kaupke, J.

AU - Kaveh, K.

AU - Kaye, W.

AU - Keightley, G. E.

AU - Keith, K.

AU - Khairullah, Q.

AU - Kondle, V.

AU - Kopyt, N.

AU - Krishna, G.

AU - Lawrence, M. K.

AU - LeBeau, M.

AU - Leehey, D. J.

AU - Levine, M. M.

AU - Levinson, D.

AU - Lew, S. Q.

AU - Lewis, D.

AU - Linfert, D.

AU - Liss, K.

AU - Lund, R.

AU - Madeleine, P.

AU - Mahmood, K.

AU - Martin, E. R.

AU - Martinez, C.

AU - Mayeda, S. O.

AU - Mendez, R.

AU - Middleton, J.

AU - Molitch, M. E.

AU - Moncrief, J.

AU - Moustafa, M.

AU - Muoneke, R.

AU - Murray, A. V.

AU - Murugan, T. S.

AU - Nammour, T. M.

AU - Nassar, G.

AU - Navaneethan, S.

AU - Newman, J.

AU - Nossuli, A.

AU - Nwakoby, I.

AU - Osama, S.

AU - Ouseph, R.

AU - Parker, J.

AU - Parnes, E.

AU - Patel, N.

AU - Pergola, P.

AU - Perlman, A.

AU - Perry, R. G.

AU - Petrillo, R.

AU - Prabhakar, S.

AU - Purighalla, R. S.

AU - Quesada-Suarez, L.

AU - Rabiei, A.

AU - Raskin, P.

AU - Rastogi, A.

AU - Reisin, E.

AU - Rekhi, A.

AU - Rivera-Colon, L.

AU - Rizk, D.

AU - Rodelas, R.

AU - Roer, D.

AU - Rosas, S.

AU - Ross, D. L.

AU - Rovner, S.

AU - Sackel, H.

AU - Sader, S.

AU - Santos, P.

AU - Schmidt, R.

AU - Shafik, S.

AU - Shakeel, M.

AU - Sharon, Z.

AU - Silva, A. L.

AU - Silva, A.

AU - Singh, B.

AU - Smith, M.

AU - Solomon, R.

AU - Soman, S.

AU - Spinowitz, B.

AU - Sprague, S. M.

AU - Spry, L.

AU - Stonesifer, L.

AU - Streja, D.

AU - Suchinda, P.

AU - Sun, C.

AU - Thakar, C. V.

AU - Trespalacios, F.

AU - Tumlin, J. A.

AU - Van Buren, P.

AU - Vernace, M.

AU - Vicks, S.

AU - Warren, M.

AU - Weiss, D.

AU - Welker, J.

AU - Winston, J. A.

AU - Wombolt, D. G.

AU - Wood, M.

AU - Wu, M.

AU - Wynne, A.

AU - Yu, H.

AU - Zabaneh, R. I.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - BACKGROUND: Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown. METHODS: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. RESULTS: The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. CONCLUSIONS: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial.

AB - BACKGROUND: Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown. METHODS: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. RESULTS: The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. CONCLUSIONS: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial.

UR - http://www.scopus.com/inward/record.url?scp=84890946148&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1306033

DO - 10.1056/NEJMoa1306033

M3 - Article

VL - 369

SP - 2492

EP - 2503

JO - New England Journal of Medicine

T2 - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 26

ER -

De Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. New England Journal of Medicine. 2013 Jan 1;369(26):2492-2503. https://doi.org/10.1056/NEJMoa1306033