International consensus definitions of clinical trial outcomes for kidney failure: 2020

Adeera Levin; Rajiv Agarwal; William G. Herrington; Hiddo L. Heerspink; Johannes F.E. Mann; Shahnaz Shahinfar; Katherine R. Tuttle; Jo Ann Donner; Vivekanand Jha; Masaomi Nangaku; Dick de Zeeuw; Meg J. Jardine; Kenneth W. Mahaffey; Aliza M. Thompson; Mary Beaucage; Kate Chong; Glenda V. Roberts; Duane Sunwold; Hans Vorster; Madeleine Warren; Sandrine Damster; Charu Malik; Vlado Perkovic; Shuchi Anand; Nicholas Argent; Elena Babak; Debasish Banerjee; Jonathan Barratt; Aminu K. Bello; Angelito A. Bernardo; Jaime Blais; William Canovatchel; Fergus J. Caskey; Josef Coresh; Ian H. de Boer; Kai Uwe Eckardt; Rhys DR Evans; Harold I. Feldman; Agnes B. Fogo; Hrefna Gudmundsdottir; Takayuki Hamano; David C.H. Harris; Sibylle J. Hauske; Richard Haynes; Charles A. Herzog; Thomas Hiemstra; Thomas Idorn; Lesley Inker; Julie H. Ishida; David W. Johnson; Charlotte Jones-Burton; Amer Joseph; Audrey Koitka-Weber; Matthias Kretzler; Robert Lawatscheck; Adrian Liew; Louise Moist; Saraladevi Naicker; Reiko Nakashima; Uptal Patel; Roberto Pecoits Filho; Jennifer B. Rose; Noah L. Rosenberg; Marvin Sinsakul; William E. Smoyer; Laura Sola; Amy R. Sood; Benedicte Stengel; Maarten W. Taal; Mototsugu Tanaka; Marcello Tonelli; Allison Tong; Robert Toto; Michele Trask; Ifeoma I. Ulasi; Christoph Wanner; David C. Wheeler; Benjamin O. Wolthers; Harold M. Wright; Yoshihisa Yamada; Elena Zakharova

doi:10.1016/j.kint.2020.07.013

International consensus definitions of clinical trial outcomes for kidney failure: 2020

Adeera Levin, Rajiv Agarwal, William G. Herrington, Hiddo L. Heerspink, Johannes F.E. Mann, Shahnaz Shahinfar, Katherine R. Tuttle, Jo Ann Donner, Vivekanand Jha, Masaomi Nangaku, Dick de Zeeuw, Meg J. Jardine, Kenneth W. Mahaffey, Aliza M. Thompson, Mary Beaucage, Kate Chong, Glenda V. Roberts, Duane Sunwold, Hans Vorster, Madeleine WarrenSandrine Damster, Charu Malik, Vlado Perkovic, Shuchi Anand, Nicholas Argent, Elena Babak, Debasish Banerjee, Jonathan Barratt, Aminu K. Bello, Angelito A. Bernardo, Jaime Blais, William Canovatchel, Fergus J. Caskey, Josef Coresh, Ian H. de Boer, Kai Uwe Eckardt, Rhys DR Evans, Harold I. Feldman, Agnes B. Fogo, Hrefna Gudmundsdottir, Takayuki Hamano, David C.H. Harris, Sibylle J. Hauske, Richard Haynes, Charles A. Herzog, Thomas Hiemstra, Thomas Idorn, Lesley Inker, Julie H. Ishida, David W. Johnson, Charlotte Jones-Burton, Amer Joseph, Audrey Koitka-Weber, Matthias Kretzler, Robert Lawatscheck, Adrian Liew, Louise Moist, Saraladevi Naicker, Reiko Nakashima, Uptal Patel, Roberto Pecoits Filho, Jennifer B. Rose, Noah L. Rosenberg, Marvin Sinsakul, William E. Smoyer, Laura Sola, Amy R. Sood, Benedicte Stengel, Maarten W. Taal, Mototsugu Tanaka, Marcello Tonelli, Allison Tong, Robert Toto, Michele Trask, Ifeoma I. Ulasi, Christoph Wanner, David C. Wheeler, Benjamin O. Wolthers, Harold M. Wright, Yoshihisa Yamada, Elena Zakharova

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.

Original language	English (US)
Pages (from-to)	849-859
Number of pages	11
Journal	Kidney international
Volume	98
Issue number	4
DOIs	https://doi.org/10.1016/j.kint.2020.07.013
State	Published - Oct 2020

Keywords

continuous kidney replacement therapy
kidney failure
maintenance dialysis
transplantation

ASJC Scopus subject areas

Nephrology

Access to Document

10.1016/j.kint.2020.07.013

Cite this

Levin, A., Agarwal, R., Herrington, W. G., Heerspink, H. L., Mann, J. F. E., Shahinfar, S., Tuttle, K. R., Donner, J. A., Jha, V., Nangaku, M., de Zeeuw, D., Jardine, M. J., Mahaffey, K. W., Thompson, A. M., Beaucage, M., Chong, K., Roberts, G. V., Sunwold, D., Vorster, H., ... Zakharova, E. (2020). International consensus definitions of clinical trial outcomes for kidney failure: 2020. Kidney international, 98(4), 849-859. https://doi.org/10.1016/j.kint.2020.07.013

Levin, A, Agarwal, R, Herrington, WG, Heerspink, HL, Mann, JFE, Shahinfar, S, Tuttle, KR, Donner, JA, Jha, V, Nangaku, M, de Zeeuw, D, Jardine, MJ, Mahaffey, KW, Thompson, AM, Beaucage, M, Chong, K, Roberts, GV, Sunwold, D, Vorster, H, Warren, M, Damster, S, Malik, C, Perkovic, V, Anand, S, Argent, N, Babak, E, Banerjee, D, Barratt, J, Bello, AK, Bernardo, AA, Blais, J, Canovatchel, W, Caskey, FJ, Coresh, J, de Boer, IH, Eckardt, KU, Evans, RDR, Feldman, HI, Fogo, AB, Gudmundsdottir, H, Hamano, T, Harris, DCH, Hauske, SJ, Haynes, R, Herzog, CA, Hiemstra, T, Idorn, T, Inker, L, Ishida, JH, Johnson, DW, Jones-Burton, C, Joseph, A, Koitka-Weber, A, Kretzler, M, Lawatscheck, R, Liew, A, Moist, L, Naicker, S, Nakashima, R, Patel, U, Filho, RP, Rose, JB, Rosenberg, NL, Sinsakul, M, Smoyer, WE, Sola, L, Sood, AR, Stengel, B, Taal, MW, Tanaka, M, Tonelli, M, Tong, A, Toto, R, Trask, M, Ulasi, II, Wanner, C, Wheeler, DC, Wolthers, BO, Wright, HM, Yamada, Y & Zakharova, E 2020, 'International consensus definitions of clinical trial outcomes for kidney failure: 2020', Kidney international, vol. 98, no. 4, pp. 849-859. https://doi.org/10.1016/j.kint.2020.07.013

@article{0e9ff0d50e5a474eb76e47c9d4544c1e,

title = "International consensus definitions of clinical trial outcomes for kidney failure: 2020",

abstract = "Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.",

keywords = "continuous kidney replacement therapy, kidney failure, maintenance dialysis, transplantation",

author = "Adeera Levin and Rajiv Agarwal and Herrington, {William G.} and Heerspink, {Hiddo L.} and Mann, {Johannes F.E.} and Shahnaz Shahinfar and Tuttle, {Katherine R.} and Donner, {Jo Ann} and Vivekanand Jha and Masaomi Nangaku and {de Zeeuw}, Dick and Jardine, {Meg J.} and Mahaffey, {Kenneth W.} and Thompson, {Aliza M.} and Mary Beaucage and Kate Chong and Roberts, {Glenda V.} and Duane Sunwold and Hans Vorster and Madeleine Warren and Sandrine Damster and Charu Malik and Vlado Perkovic and Shuchi Anand and Nicholas Argent and Elena Babak and Debasish Banerjee and Jonathan Barratt and Bello, {Aminu K.} and Bernardo, {Angelito A.} and Jaime Blais and William Canovatchel and Caskey, {Fergus J.} and Josef Coresh and {de Boer}, {Ian H.} and Eckardt, {Kai Uwe} and Evans, {Rhys DR} and Feldman, {Harold I.} and Fogo, {Agnes B.} and Hrefna Gudmundsdottir and Takayuki Hamano and Harris, {David C.H.} and Hauske, {Sibylle J.} and Richard Haynes and Herzog, {Charles A.} and Thomas Hiemstra and Thomas Idorn and Lesley Inker and Ishida, {Julie H.} and Johnson, {David W.} and Charlotte Jones-Burton and Amer Joseph and Audrey Koitka-Weber and Matthias Kretzler and Robert Lawatscheck and Adrian Liew and Louise Moist and Saraladevi Naicker and Reiko Nakashima and Uptal Patel and Filho, {Roberto Pecoits} and Rose, {Jennifer B.} and Rosenberg, {Noah L.} and Marvin Sinsakul and Smoyer, {William E.} and Laura Sola and Sood, {Amy R.} and Benedicte Stengel and Taal, {Maarten W.} and Mototsugu Tanaka and Marcello Tonelli and Allison Tong and Robert Toto and Michele Trask and Ulasi, {Ifeoma I.} and Christoph Wanner and Wheeler, {David C.} and Wolthers, {Benjamin O.} and Wright, {Harold M.} and Yoshihisa Yamada and Elena Zakharova",

note = "Funding Information: Support for the 1st International Consensus Meeting on Defining Kidney Failure in Clinical Trials was made possible by various organizations (listed in alphabetical order): AstraZeneca LP, Baxter, Bayer, Boehringer Ingelheim, Gilead, Janssen Inc. (a pharmaceutical company of Johnson & Johnson), Novo Nordisk, Otsuka, REATA, Retrophin, and Tourism Vancouver. In addition, support “in kind” was provided from Can-SOLVE CKD Network (CIHR SPOR Network), and those representing regulatory bodies, national research organizations, or other research organizations that supported representative attendance at the meeting. The International Society of Nephrology thanks the following people and organizations for reviewing the manuscript: Dr. Robert Star; Dr. Rosanna Coppo; Dr. Hong Zhang; the Venezuelan Society of Nephrology; the Russian Dialysis Society; the Canadian Nephrology Trials Network; the Japanese Society of Nephrology; the Korean Society of Nephrology; the French Society of Nephrology, Dialysis and Transplantation; the Hellenic Society of Nephrology; the Norwegian Society of Nephrology; the Swedish Society of Nephrology; the Renal Association; and the Nigerian Association of Nephrology. This work was supported by the International Society of Nephrology. The views expressed in this article are solely the responsibility of the authors and they do not necessarily reflect the views, decisions, or policies of the institutions with which they are affiliated. Funding Information: SA reports grants from Normon S. Coplon Satellite Healthcare Applied Pragmatic Research Grant, outside the submitted work. EB reports personal fees from AstraZeneca Canada, outside the submitted work. DB reports grants from Wellcome ISSF 204809/Z/16/Z, Kidney Research UK ID-01520190403, and AstraZeneca ESR ESR-19-20174, outside the submitted work. AAB reports personal fees from Baxter Healthcare Corporation, outside the submitted work. WC reports personal fees from Johnson & Johnson, outside the submitted work. FC reports personal fees from Baxter Healthcare, outside the submitted work. ID reports personal fees from Boehringher-Ingelheim, George Clinical, Goldfinch Bio, and Ironwood, outside the submitted work. KE reports grants from AstraZeneca, Bayer, Fresenius, Vifor, Amgen, Genzyme, and Shire, and personal fees from Akebia, Bayer, Fresenius, and Vifor, outside the submitted work. HF reports grant from the National Institutes of Health, personal fees from the National Kidney Foundation, Kyowa Kirin Inc., and InMed, Inc., and honorarium from the University of California, Los Angeles, outside the submitted work. SH reports personal fees from Boehringer Ingelheim, outside the submitted work. RH reports grants from Boehringer Ingelheim and Novartis, outside the submitted work. CH reports personal fees from AbbVie, AstraZeneca, Corvidia, Diamedica, FibroGen, Janssen, NxStage, Pfizer, Sanifit, University of Oxford, and UpToDate, a grant from the National Institute of Diabetes and Digestive and Kidney Diseases /National Institutes of Health (USRDS Contract), a grant and personal fees from Amgen, Relypsa, Inc., and the National Heart Lung and Blood Institute (NHLBI/NIH), a grant and stocks from Bristol-Meyer Squibb, personal fees and stock from Merck, a grant from the University of British Columbia, and stocks from Boston Scientific, General Electric, Johnson & Johnson, and Hennepin Healthcare, outside the submitted work. LI reports grants from Retrophin and Reata Pharmaceuticals, a grant and consulting agreement from Omeros Corporation, and a consulting agreement with Tricida, Inc., outside the submitted work. JI reports personal fees from Gilead Sciences, Inc., outside the submitted work; and is a volunteer Workgroup Co-Chair for the Kidney Health Initiative. DWJ reports grants and personal fees from Baxter Healthcare and Fresenius Medical Care, personal fees from AstraZeneca, AWAK, and Ono, travel sponsorship from Amgen, and a grant from the National Health and Medical Research Council of Australia, personal fees from Ono, outside the submitted work. CJB reports personal fees from Otsuka Pharmaceutical Development & Commercialization, Inc., outside the submitted work. AJ reports personal fees from Bayer AG, outside the submitted work. AKW reports personal fees from Boehringer Ingelheim, outside the submitted work. MK reports grants from AstraZeneca, Gilead Sciences, Inc., Novo Nordisk, Eli Lilly and Co., Janssen, Merck, Elpidera, Certa, Goldfinch Bio, Boehringer Ingelheim, the National Institutes of Health, JDRF, and Angion, outside the submitted work, and has a patent PCT/EP2014/073413 “Biomarkers and methods for progression prediction for chronic kidney disease” issued. RL reports personal fees and other stocks from Bayer AG, outside the submitted work. SN reports a research grant funded by the Newton Fund, Medical Research Council (UK and South Africa), and GlaxoSmithKline, outside the submitted work. UP reports personal fees from Gilead Sciences, Inc., outside the submitted work and is a member of the Board of Directors for Kidney Health Initiative. RPF reports grants from Baxter Healthcare and Fresenius Medical Care, personal fees from AstraZeneca and Akebia, outside the submitted work. JR reports personal fees and stock from Janssen Inc., Canada, outside the submitted work. NR reports personal fees Retrophin, Inc., outside the submitted work. MS reports personal fees and other stocks from AstraZeneca, outside the submitted work. CW reports grant from Boehringer-Ingelheim, personal fees from Boehringer-Ingelheim, Gilead Sciences, Inc., GlaxoSmithKline, and MSD, outside the submitted work. DW reports personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Napp, Mundipharma, Reata, Vifor Fresenius, and Merck Sharpe and Dohme, outside the submitted work. BW reports personal fees Novo Nordisk A/S, outside the submitted work. HW reports personal fees and stocks from Retrophin, Inc., outside the submitted work. YY reports personal fees and stocks from Otsuka Pharmaceutical Co., Ltd., outside the submitted work. All the other authors declared no competing interests. Funding Information: RA reports personal fees and travel support from Relypsa, Inc., AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly and Co., Gilead Sciences, Inc., GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Sandoz, ZS Pharma, Inc., Akebia, Takeda, Sanofi, Reata, Ironwood Pharmaceuticals, Otsuka, Opko, and Birdrock Bio; and grants from the National Institutes of Health (NIH) and the Veterans Administration Medical Center, outside the submitted work. SD reports personal fees from The International Society of Nephrology, outside the submitted work. DDZ reports advisory and speaker fees to himself and his institution from Fresenius, Boehringer Ingelheim, and Bayer; Steering Committee fees to himself and his institution from Janssen; advisory and speaker fees from Mitsubishi Tanabe and Mundipharma; and Steering Committee fees to his institution from AbbVie, outside the submitted work. JD reports personal fees from The International Society of Nephrology, outside the submitted work. HLH reports personal fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Bayer, Chinook, CSL Behring, Fresenius, Janssen, Gilead Sciences, Inc., Merck, Mitsubishi Pharma, and Retrophin; and grant support from AstraZeneca, Boehringer Ingelheim, and Janssen, outside the submitted work. WH reports grants from Boehringer Ingelheim, Eli Lilly and Co., Novartis, Medical Research Council UK, and Kidney Research UK, outside the submitted work (and is supported by an MRC-Kidney Research UK Professor David Kerr award). MJ reports consultancy fees, honoraria, and/or travel support paid to her institution from Akebia, Amgen, AstraZeneca, Baxter, Boehringer Ingelheim, Commonwealth Serum Laboratories, and Vifor, outside the submitted work. VJ reports grants from GlaxoSmithKline and Baxter Healthcare, and provides scientific leadership to George Clinical and consultancy for Biocon, Zudis Cadilla, and NephroPlus, outside the submitted work. KM reports personal fees from Abbott, Ablynx, Baim Institute, Boehringer Ingelheim, Bristol Myers Squibb, Elsevier, GlaxoSmithKline, Medergy, Medscape, Mitsubishi, Myokardia, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, and University of California, San Francisco; grants and personal fees from AstraZeneca, Johnson & Johnson, the National Institutes of Health (NIH), and Novartis; and grants from Afferent, Amgen, Apple, Inc., Cardiva Medical, Inc., Daiichi, Ferring, Google (Verily), Luitpold, Medtronic, Merck, Sanofi, St. Jude, and Tenax, outside the submitted work. CM reports personal fees from The International Society of Nephrology, outside the submitted work. MN reports grants and personal fees from Kyowa Kirin, Astellas, Daiichi Sankyo, Mitsubishi Tanabe, JT, Chugai, Takeda, and MSD; personal fees from GlaxoSmithKline, Boehringer Ingelheim, Torii, AstraZeneca, Akebia, and Bayer; grants from Ono, Ostuaka, Dainippon Sumitomo, outside the submitted work. SS reports personal fees from Amgen, Johnson & Johnson, and Tricida, Inc., outside the submitted work. KT reports personal fees from Eli Lilly and Co., Boehringer Ingelheim, AstraZeneca, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk, and Bayer, outside the submitted work. MW reports personal fees from Quanta Dialysis Technologies, Pathfinder Medical, and Clinical Reference Group (National Health Service England), outside the submitted work. VP reports personal fees from Servier, Retrophin, Merck, and Janssen; a Research Fellowship from the National Health and Medical Research Council; a grant from the National Health and Medical Research Council paid to his institution; grants, honoraria, and support for clinical trials from GlaxoSmithKline, Pfizer, and Janssen paid to his institution; and advisory fees, honoraria, and/or travel support paid to his institution from Bayer, Bristol-Myers Squibb Company, Eli Lilly and Co., Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Pharmalink, Relypsa, Inc., Baxter, Sanofi, Gilead Sciences, Inc., Novartis, Durect, Astellas, Tricida, Inc., Dimetrix, and AbbVie. All the other authors declared no competing interests. Publisher Copyright: {\textcopyright} 2020 International Society of Nephrology",

year = "2020",

month = oct,

doi = "10.1016/j.kint.2020.07.013",

language = "English (US)",

volume = "98",

pages = "849--859",

journal = "Kidney international",

issn = "0085-2538",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - International consensus definitions of clinical trial outcomes for kidney failure

T2 - 2020

AU - Levin, Adeera

AU - Agarwal, Rajiv

AU - Herrington, William G.

AU - Heerspink, Hiddo L.

AU - Mann, Johannes F.E.

AU - Shahinfar, Shahnaz

AU - Tuttle, Katherine R.

AU - Donner, Jo Ann

AU - Jha, Vivekanand

AU - Nangaku, Masaomi

AU - de Zeeuw, Dick

AU - Jardine, Meg J.

AU - Mahaffey, Kenneth W.

AU - Thompson, Aliza M.

AU - Beaucage, Mary

AU - Chong, Kate

AU - Roberts, Glenda V.

AU - Sunwold, Duane

AU - Vorster, Hans

AU - Warren, Madeleine

AU - Damster, Sandrine

AU - Malik, Charu

AU - Perkovic, Vlado

AU - Anand, Shuchi

AU - Argent, Nicholas

AU - Babak, Elena

AU - Banerjee, Debasish

AU - Barratt, Jonathan

AU - Bello, Aminu K.

AU - Bernardo, Angelito A.

AU - Blais, Jaime

AU - Canovatchel, William

AU - Caskey, Fergus J.

AU - Coresh, Josef

AU - de Boer, Ian H.

AU - Eckardt, Kai Uwe

AU - Evans, Rhys DR

AU - Feldman, Harold I.

AU - Fogo, Agnes B.

AU - Gudmundsdottir, Hrefna

AU - Hamano, Takayuki

AU - Harris, David C.H.

AU - Hauske, Sibylle J.

AU - Haynes, Richard

AU - Herzog, Charles A.

AU - Hiemstra, Thomas

AU - Idorn, Thomas

AU - Inker, Lesley

AU - Ishida, Julie H.

AU - Johnson, David W.

AU - Jones-Burton, Charlotte

AU - Joseph, Amer

AU - Koitka-Weber, Audrey

AU - Kretzler, Matthias

AU - Lawatscheck, Robert

AU - Liew, Adrian

AU - Moist, Louise

AU - Naicker, Saraladevi

AU - Nakashima, Reiko

AU - Patel, Uptal

AU - Filho, Roberto Pecoits

AU - Rose, Jennifer B.

AU - Rosenberg, Noah L.

AU - Sinsakul, Marvin

AU - Smoyer, William E.

AU - Sola, Laura

AU - Sood, Amy R.

AU - Stengel, Benedicte

AU - Taal, Maarten W.

AU - Tanaka, Mototsugu

AU - Tonelli, Marcello

AU - Tong, Allison

AU - Toto, Robert

AU - Trask, Michele

AU - Ulasi, Ifeoma I.

AU - Wanner, Christoph

AU - Wheeler, David C.

AU - Wolthers, Benjamin O.

AU - Wright, Harold M.

AU - Yamada, Yoshihisa

AU - Zakharova, Elena

N1 - Funding Information: Support for the 1st International Consensus Meeting on Defining Kidney Failure in Clinical Trials was made possible by various organizations (listed in alphabetical order): AstraZeneca LP, Baxter, Bayer, Boehringer Ingelheim, Gilead, Janssen Inc. (a pharmaceutical company of Johnson & Johnson), Novo Nordisk, Otsuka, REATA, Retrophin, and Tourism Vancouver. In addition, support “in kind” was provided from Can-SOLVE CKD Network (CIHR SPOR Network), and those representing regulatory bodies, national research organizations, or other research organizations that supported representative attendance at the meeting. The International Society of Nephrology thanks the following people and organizations for reviewing the manuscript: Dr. Robert Star; Dr. Rosanna Coppo; Dr. Hong Zhang; the Venezuelan Society of Nephrology; the Russian Dialysis Society; the Canadian Nephrology Trials Network; the Japanese Society of Nephrology; the Korean Society of Nephrology; the French Society of Nephrology, Dialysis and Transplantation; the Hellenic Society of Nephrology; the Norwegian Society of Nephrology; the Swedish Society of Nephrology; the Renal Association; and the Nigerian Association of Nephrology. This work was supported by the International Society of Nephrology. The views expressed in this article are solely the responsibility of the authors and they do not necessarily reflect the views, decisions, or policies of the institutions with which they are affiliated. Funding Information: SA reports grants from Normon S. Coplon Satellite Healthcare Applied Pragmatic Research Grant, outside the submitted work. EB reports personal fees from AstraZeneca Canada, outside the submitted work. DB reports grants from Wellcome ISSF 204809/Z/16/Z, Kidney Research UK ID-01520190403, and AstraZeneca ESR ESR-19-20174, outside the submitted work. AAB reports personal fees from Baxter Healthcare Corporation, outside the submitted work. WC reports personal fees from Johnson & Johnson, outside the submitted work. FC reports personal fees from Baxter Healthcare, outside the submitted work. ID reports personal fees from Boehringher-Ingelheim, George Clinical, Goldfinch Bio, and Ironwood, outside the submitted work. KE reports grants from AstraZeneca, Bayer, Fresenius, Vifor, Amgen, Genzyme, and Shire, and personal fees from Akebia, Bayer, Fresenius, and Vifor, outside the submitted work. HF reports grant from the National Institutes of Health, personal fees from the National Kidney Foundation, Kyowa Kirin Inc., and InMed, Inc., and honorarium from the University of California, Los Angeles, outside the submitted work. SH reports personal fees from Boehringer Ingelheim, outside the submitted work. RH reports grants from Boehringer Ingelheim and Novartis, outside the submitted work. CH reports personal fees from AbbVie, AstraZeneca, Corvidia, Diamedica, FibroGen, Janssen, NxStage, Pfizer, Sanifit, University of Oxford, and UpToDate, a grant from the National Institute of Diabetes and Digestive and Kidney Diseases /National Institutes of Health (USRDS Contract), a grant and personal fees from Amgen, Relypsa, Inc., and the National Heart Lung and Blood Institute (NHLBI/NIH), a grant and stocks from Bristol-Meyer Squibb, personal fees and stock from Merck, a grant from the University of British Columbia, and stocks from Boston Scientific, General Electric, Johnson & Johnson, and Hennepin Healthcare, outside the submitted work. LI reports grants from Retrophin and Reata Pharmaceuticals, a grant and consulting agreement from Omeros Corporation, and a consulting agreement with Tricida, Inc., outside the submitted work. JI reports personal fees from Gilead Sciences, Inc., outside the submitted work; and is a volunteer Workgroup Co-Chair for the Kidney Health Initiative. DWJ reports grants and personal fees from Baxter Healthcare and Fresenius Medical Care, personal fees from AstraZeneca, AWAK, and Ono, travel sponsorship from Amgen, and a grant from the National Health and Medical Research Council of Australia, personal fees from Ono, outside the submitted work. CJB reports personal fees from Otsuka Pharmaceutical Development & Commercialization, Inc., outside the submitted work. AJ reports personal fees from Bayer AG, outside the submitted work. AKW reports personal fees from Boehringer Ingelheim, outside the submitted work. MK reports grants from AstraZeneca, Gilead Sciences, Inc., Novo Nordisk, Eli Lilly and Co., Janssen, Merck, Elpidera, Certa, Goldfinch Bio, Boehringer Ingelheim, the National Institutes of Health, JDRF, and Angion, outside the submitted work, and has a patent PCT/EP2014/073413 “Biomarkers and methods for progression prediction for chronic kidney disease” issued. RL reports personal fees and other stocks from Bayer AG, outside the submitted work. SN reports a research grant funded by the Newton Fund, Medical Research Council (UK and South Africa), and GlaxoSmithKline, outside the submitted work. UP reports personal fees from Gilead Sciences, Inc., outside the submitted work and is a member of the Board of Directors for Kidney Health Initiative. RPF reports grants from Baxter Healthcare and Fresenius Medical Care, personal fees from AstraZeneca and Akebia, outside the submitted work. JR reports personal fees and stock from Janssen Inc., Canada, outside the submitted work. NR reports personal fees Retrophin, Inc., outside the submitted work. MS reports personal fees and other stocks from AstraZeneca, outside the submitted work. CW reports grant from Boehringer-Ingelheim, personal fees from Boehringer-Ingelheim, Gilead Sciences, Inc., GlaxoSmithKline, and MSD, outside the submitted work. DW reports personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Napp, Mundipharma, Reata, Vifor Fresenius, and Merck Sharpe and Dohme, outside the submitted work. BW reports personal fees Novo Nordisk A/S, outside the submitted work. HW reports personal fees and stocks from Retrophin, Inc., outside the submitted work. YY reports personal fees and stocks from Otsuka Pharmaceutical Co., Ltd., outside the submitted work. All the other authors declared no competing interests. Funding Information: RA reports personal fees and travel support from Relypsa, Inc., AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly and Co., Gilead Sciences, Inc., GlaxoSmithKline, Johnson & Johnson, Merck, Novartis, Sandoz, ZS Pharma, Inc., Akebia, Takeda, Sanofi, Reata, Ironwood Pharmaceuticals, Otsuka, Opko, and Birdrock Bio; and grants from the National Institutes of Health (NIH) and the Veterans Administration Medical Center, outside the submitted work. SD reports personal fees from The International Society of Nephrology, outside the submitted work. DDZ reports advisory and speaker fees to himself and his institution from Fresenius, Boehringer Ingelheim, and Bayer; Steering Committee fees to himself and his institution from Janssen; advisory and speaker fees from Mitsubishi Tanabe and Mundipharma; and Steering Committee fees to his institution from AbbVie, outside the submitted work. JD reports personal fees from The International Society of Nephrology, outside the submitted work. HLH reports personal fees from AbbVie, AstraZeneca, Boehringer Ingelheim, Bayer, Chinook, CSL Behring, Fresenius, Janssen, Gilead Sciences, Inc., Merck, Mitsubishi Pharma, and Retrophin; and grant support from AstraZeneca, Boehringer Ingelheim, and Janssen, outside the submitted work. WH reports grants from Boehringer Ingelheim, Eli Lilly and Co., Novartis, Medical Research Council UK, and Kidney Research UK, outside the submitted work (and is supported by an MRC-Kidney Research UK Professor David Kerr award). MJ reports consultancy fees, honoraria, and/or travel support paid to her institution from Akebia, Amgen, AstraZeneca, Baxter, Boehringer Ingelheim, Commonwealth Serum Laboratories, and Vifor, outside the submitted work. VJ reports grants from GlaxoSmithKline and Baxter Healthcare, and provides scientific leadership to George Clinical and consultancy for Biocon, Zudis Cadilla, and NephroPlus, outside the submitted work. KM reports personal fees from Abbott, Ablynx, Baim Institute, Boehringer Ingelheim, Bristol Myers Squibb, Elsevier, GlaxoSmithKline, Medergy, Medscape, Mitsubishi, Myokardia, Novo Nordisk, Portola, Radiometer, Regeneron, SmartMedics, Springer Publishing, and University of California, San Francisco; grants and personal fees from AstraZeneca, Johnson & Johnson, the National Institutes of Health (NIH), and Novartis; and grants from Afferent, Amgen, Apple, Inc., Cardiva Medical, Inc., Daiichi, Ferring, Google (Verily), Luitpold, Medtronic, Merck, Sanofi, St. Jude, and Tenax, outside the submitted work. CM reports personal fees from The International Society of Nephrology, outside the submitted work. MN reports grants and personal fees from Kyowa Kirin, Astellas, Daiichi Sankyo, Mitsubishi Tanabe, JT, Chugai, Takeda, and MSD; personal fees from GlaxoSmithKline, Boehringer Ingelheim, Torii, AstraZeneca, Akebia, and Bayer; grants from Ono, Ostuaka, Dainippon Sumitomo, outside the submitted work. SS reports personal fees from Amgen, Johnson & Johnson, and Tricida, Inc., outside the submitted work. KT reports personal fees from Eli Lilly and Co., Boehringer Ingelheim, AstraZeneca, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk, and Bayer, outside the submitted work. MW reports personal fees from Quanta Dialysis Technologies, Pathfinder Medical, and Clinical Reference Group (National Health Service England), outside the submitted work. VP reports personal fees from Servier, Retrophin, Merck, and Janssen; a Research Fellowship from the National Health and Medical Research Council; a grant from the National Health and Medical Research Council paid to his institution; grants, honoraria, and support for clinical trials from GlaxoSmithKline, Pfizer, and Janssen paid to his institution; and advisory fees, honoraria, and/or travel support paid to his institution from Bayer, Bristol-Myers Squibb Company, Eli Lilly and Co., Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Pharmalink, Relypsa, Inc., Baxter, Sanofi, Gilead Sciences, Inc., Novartis, Durect, Astellas, Tricida, Inc., Dimetrix, and AbbVie. All the other authors declared no competing interests. Publisher Copyright: © 2020 International Society of Nephrology

PY - 2020/10

Y1 - 2020/10

N2 - Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.

AB - Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.

KW - continuous kidney replacement therapy

KW - kidney failure

KW - maintenance dialysis

KW - transplantation

UR - http://www.scopus.com/inward/record.url?scp=85091763954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85091763954&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2020.07.013

DO - 10.1016/j.kint.2020.07.013

M3 - Article

C2 - 32998816

AN - SCOPUS:85091763954

SN - 0085-2538

VL - 98

SP - 849

EP - 859

JO - Kidney international

JF - Kidney international

IS - 4

ER -

International consensus definitions of clinical trial outcomes for kidney failure: 2020

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