Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: Post-hoc analysis of the kremezin study against renal disease progression in Korea

Ran Hui Cha, Shin-Wook Kang, Cheol Whee Park, Dae Ryong Cha, Ki Young Na, Sung Gyun Kim, Sun Ae Yoon, Sejoong Kim, Sang Youb Han, Jung Hwan Park, Jae Hyun Chang, Chun Soo Lim, Yon Su Kim

Research output: Contribution to journalArticle

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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 performed post-hoc analysis 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-rank P = 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)68-78
Number of pages11
JournalKidney Research and Clinical Practice
Volume36
Issue number1
DOIs
Publication statusPublished - 2017 Mar 1

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Korea
Disease Progression
Kidney
Confidence Intervals
Indican
AST 120
Serum
Glomerular Filtration Rate
Chronic Renal Insufficiency
Compliance

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Urology

Cite this

Cha, Ran Hui ; Kang, Shin-Wook ; Park, Cheol Whee ; Cha, Dae Ryong ; Na, Ki Young ; Kim, Sung Gyun ; Yoon, Sun Ae ; Kim, Sejoong ; Han, Sang Youb ; Park, Jung Hwan ; Chang, Jae Hyun ; Lim, Chun Soo ; Kim, Yon Su. / Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction : Post-hoc analysis of the kremezin study against renal disease progression in Korea. In: Kidney Research and Clinical Practice. 2017 ; Vol. 36, No. 1. pp. 68-78.
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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 performed post-hoc analysis 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-rank P = 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). Conclusion: 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.",
author = "Cha, {Ran Hui} and Shin-Wook Kang and Park, {Cheol Whee} and Cha, {Dae Ryong} and Na, {Ki Young} and Kim, {Sung Gyun} and Yoon, {Sun Ae} and Sejoong Kim and Han, {Sang Youb} and Park, {Jung Hwan} and Chang, {Jae Hyun} and Lim, {Chun Soo} and Kim, {Yon Su}",
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Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction : Post-hoc analysis of the kremezin study against renal disease progression in Korea. / Cha, Ran Hui; Kang, Shin-Wook; Park, Cheol Whee; Cha, Dae Ryong; Na, Ki Young; Kim, Sung Gyun; Yoon, Sun Ae; Kim, Sejoong; Han, Sang Youb; Park, Jung Hwan; Chang, Jae Hyun; Lim, Chun Soo; Kim, Yon Su.

In: Kidney Research and Clinical Practice, Vol. 36, No. 1, 01.03.2017, p. 68-78.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction

T2 - Post-hoc analysis of the kremezin study against renal disease progression in Korea

AU - Cha, Ran Hui

AU - Kang, Shin-Wook

AU - Park, Cheol Whee

AU - Cha, Dae Ryong

AU - Na, Ki Young

AU - Kim, Sung Gyun

AU - Yoon, Sun Ae

AU - Kim, Sejoong

AU - Han, Sang Youb

AU - Park, Jung Hwan

AU - Chang, Jae Hyun

AU - Lim, Chun Soo

AU - Kim, Yon Su

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 performed post-hoc analysis 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-rank P = 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). Conclusion: 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.

AB - 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 performed post-hoc analysis 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-rank P = 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). Conclusion: 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.

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