title: Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction:post-hocanalysis of the Kremezin Study against renal disease progression in Korea.
abstract: BACKGROUND
  We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD).
  
  
  METHODS
  We performedpost-hocanalysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment.
  
  
  RESULTS
  The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rankP= 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01,P= 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76,P= 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07,P= 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17,P= 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99,P= 0.046).
  
  
  CONCLUSIONS
  Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.
authors.affiliation: Department of Internal Medicine, National Medical Center, Seoul, Korea.
authors.forename: Ran-Hui
authors.initials: RH
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Shin Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
authors.forename: Cheol Whee
authors.initials: CW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Korea University Ansan-Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Cha
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hopsital, Seongnam, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ki Young
authors.initials: KY
authors.lastname: Na
authors.affiliation: Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea.
authors.forename: Sung Gyun
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Korea.
authors.forename: Sun Ae
authors.initials: SA
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hopsital, Seongnam, Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sejoong
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Goyang, Korea.
authors.forename: Sang Youb
authors.initials: SY
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea.
authors.forename: Chun Soo
authors.initials: CS
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Kidney Research Institute, Seoul National University, Seoul, Korea.
authors.forename: Yon Su
authors.initials: YS
authors.lastname: Kim
keywords: AST-120; Advanced renal dysfunction; Cardiovascular outcome; Renal outcome; Uremic toxin