Hideki Kato1, Masaomi Nangaku2, Hideki Hirakata3, Takashi Wada4, Terumasa Hayashi5, Hiroshi Sato6, Yasushi Yamazaki7, Takao Masaki8, Tatsuo Kagimura9, Hiroyasu Yamamoto10, Hiroki Hase11, Masahiro Kamouchi12, Enyu Imai13, Kyoichi Mizuno14, Manabu Iwasaki15, Tadao Akizawa16, Yoshiharu Tsubakihara17, Shoichi Maruyama18, Ichiei Narita19. 1. Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan. 2. Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655, Japan. mnangaku-tky@umin.ac.jp. 3. Fukuoka Renal Clinic, Fukuoka, Fukuoka, Japan. 4. Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan. 5. Department of Kidney Disease and Hypertension, Osaka General Medical Centre, Sumiyoshi, Osaka, Japan. 6. Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Sendai, Miyagi, Japan. 7. Department of Nephrology and Rheumatology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa, Japan. 8. Department of Nephrology, Hiroshima University Hospital, Hiroshima, Hiroshima, Japan. 9. Translational Research Informatics Center, Foundation Biomedical Research and Innovation, Kobe, Hyogo, Japan. 10. Department of Internal Medicine, Atsugi City Hospital, Atsugi, Kanagawa, Japan. 11. Division of Nephrology, Toho University Ohashi Medical Center, Meguro, Tokyo, Japan. 12. Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan. 13. Nakayamadera Imai Clinic, Takarazuka, Hyogo, Department of Nephrology, Fujita Health University Toyoake, Toyoake, Aichi, Japan. 14. Mitsukoshi Health and Welfare Foundation, Shinjuku, Tokyo, Japan. 15. Department of Computer and Information Science, Seikei University, Musashino, Tokyo, Japan. 16. Division of Nephrology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan. 17. Course of Safety Management in Health Care Sciences, Graduate School of Health Care Sciences, Jikei Institute, Yodogawa, Osaka, Japan. 18. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. 19. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata, Japan.
Abstract
BACKGROUND: Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified. METHODS: This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKD patients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index. RESULTS: The subjects consist of CKD patients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated. CONCLUSION: By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKD patients.
BACKGROUND:Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant humanerythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKDpatients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified. METHODS: This ongoing trial is a multicenter, prospective, observational study of non-dialysis CKDpatients with renal anemia. The primary objective is to survey the current realities of the therapy with ESA in Japan and evaluate the correlation between hyporesponsiveness to darbepoetin alfa and CKD progression. The secondary objective is to investigate relationship between ESA hyporesponsiveness and CVD events based on the clinical situation in Japan, and to explore an ESA response index. RESULTS: The subjects consist of CKDpatients with estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m2 who present renal anemia. The target number of registered cases is 2000 patients, based on estimates of incidences of renal and CVD events from past studies. Renal function and CVD events will be observed for 96 weeks after the initiation of darbepoetin alfa administration. Definitions of ESA hyporesponsiveness will also be investigated. CONCLUSION: By clarifying markers and factors involved in ESA hyporesponsiveness and their relationships with renal and CVD events, this ongoing study aims to improve evidence-based therapies for renal anemia in non-dialysis CKDpatients.
Authors: Scott D Solomon; Hajime Uno; Eldrin F Lewis; Kai-Uwe Eckardt; Julie Lin; Emmanuel A Burdmann; Dick de Zeeuw; Peter Ivanovich; Andrew S Levey; Patrick Parfrey; Giuseppe Remuzzi; Ajay K Singh; Robert Toto; Fannie Huang; Jerome Rossert; John J V McMurray; Marc A Pfeffer Journal: N Engl J Med Date: 2010-09-16 Impact factor: 91.245
Authors: Marc A Pfeffer; Emmanuel A Burdmann; Chao-Yin Chen; Mark E Cooper; Dick de Zeeuw; Kai-Uwe Eckardt; Jan M Feyzi; Peter Ivanovich; Reshma Kewalramani; Andrew S Levey; Eldrin F Lewis; Janet B McGill; John J V McMurray; Patrick Parfrey; Hans-Henrik Parving; Giuseppe Remuzzi; Ajay K Singh; Scott D Solomon; Robert Toto Journal: N Engl J Med Date: 2009-10-30 Impact factor: 91.245
Authors: Lynda A Szczech; Huiman X Barnhart; Jula K Inrig; Donal N Reddan; Shelly Sapp; Robert M Califf; Uptal D Patel; Ajay K Singh Journal: Kidney Int Date: 2008-07-02 Impact factor: 10.612
Authors: Rafael Lozano; Mohsen Naghavi; Kyle Foreman; Stephen Lim; Kenji Shibuya; Victor Aboyans; Jerry Abraham; Timothy Adair; Rakesh Aggarwal; Stephanie Y Ahn; Miriam Alvarado; H Ross Anderson; Laurie M Anderson; Kathryn G Andrews; Charles Atkinson; Larry M Baddour; Suzanne Barker-Collo; David H Bartels; Michelle L Bell; Emelia J Benjamin; Derrick Bennett; Kavi Bhalla; Boris Bikbov; Aref Bin Abdulhak; Gretchen Birbeck; Fiona Blyth; Ian Bolliger; Soufiane Boufous; Chiara Bucello; Michael Burch; Peter Burney; Jonathan Carapetis; Honglei Chen; David Chou; Sumeet S Chugh; Luc E Coffeng; Steven D Colan; Samantha Colquhoun; K Ellicott Colson; John Condon; Myles D Connor; Leslie T Cooper; Matthew Corriere; Monica Cortinovis; Karen Courville de Vaccaro; William Couser; Benjamin C Cowie; Michael H Criqui; Marita Cross; Kaustubh C Dabhadkar; Nabila Dahodwala; Diego De Leo; Louisa Degenhardt; Allyne Delossantos; Julie Denenberg; Don C Des Jarlais; Samath D Dharmaratne; E Ray Dorsey; Tim Driscoll; Herbert Duber; Beth Ebel; Patricia J Erwin; Patricia Espindola; Majid Ezzati; Valery Feigin; Abraham D Flaxman; Mohammad H Forouzanfar; Francis Gerry R Fowkes; Richard Franklin; Marlene Fransen; Michael K Freeman; Sherine E Gabriel; Emmanuela Gakidou; Flavio Gaspari; Richard F Gillum; Diego Gonzalez-Medina; Yara A Halasa; Diana Haring; James E Harrison; Rasmus Havmoeller; Roderick J Hay; Bruno Hoen; Peter J Hotez; Damian Hoy; Kathryn H Jacobsen; Spencer L James; Rashmi Jasrasaria; Sudha Jayaraman; Nicole Johns; Ganesan Karthikeyan; Nicholas Kassebaum; Andre Keren; Jon-Paul Khoo; Lisa Marie Knowlton; Olive Kobusingye; Adofo Koranteng; Rita Krishnamurthi; Michael Lipnick; Steven E Lipshultz; Summer Lockett Ohno; Jacqueline Mabweijano; Michael F MacIntyre; Leslie Mallinger; Lyn March; Guy B Marks; Robin Marks; Akira Matsumori; Richard Matzopoulos; Bongani M Mayosi; John H McAnulty; Mary M McDermott; John McGrath; George A Mensah; Tony R Merriman; Catherine Michaud; Matthew Miller; Ted R Miller; Charles Mock; Ana Olga Mocumbi; Ali A Mokdad; Andrew Moran; Kim Mulholland; M Nathan Nair; Luigi Naldi; K M Venkat Narayan; Kiumarss Nasseri; Paul Norman; Martin O'Donnell; Saad B Omer; Katrina Ortblad; Richard Osborne; Doruk Ozgediz; Bishnu Pahari; Jeyaraj Durai Pandian; Andrea Panozo Rivero; Rogelio Perez Padilla; Fernando Perez-Ruiz; Norberto Perico; David Phillips; Kelsey Pierce; C Arden Pope; Esteban Porrini; Farshad Pourmalek; Murugesan Raju; Dharani Ranganathan; Jürgen T Rehm; David B Rein; Guiseppe Remuzzi; Frederick P Rivara; Thomas Roberts; Felipe Rodriguez De León; Lisa C Rosenfeld; Lesley Rushton; Ralph L Sacco; Joshua A Salomon; Uchechukwu Sampson; Ella Sanman; David C Schwebel; Maria Segui-Gomez; Donald S Shepard; David Singh; Jessica Singleton; Karen Sliwa; Emma Smith; Andrew Steer; Jennifer A Taylor; Bernadette Thomas; Imad M Tleyjeh; Jeffrey A Towbin; Thomas Truelsen; Eduardo A Undurraga; N Venketasubramanian; Lakshmi Vijayakumar; Theo Vos; Gregory R Wagner; Mengru Wang; Wenzhi Wang; Kerrianne Watt; Martin A Weinstock; Robert Weintraub; James D Wilkinson; Anthony D Woolf; Sarah Wulf; Pon-Hsiu Yeh; Paul Yip; Azadeh Zabetian; Zhi-Jie Zheng; Alan D Lopez; Christopher J L Murray; Mohammad A AlMazroa; Ziad A Memish Journal: Lancet Date: 2012-12-15 Impact factor: 79.321