A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD

Gerald Schulman, Rajiv Agarwal, Muralidhar Acharya, Tomas Berl, Samuel Blumenthal, Nelson Kopyt

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Background: AST-120 (Kremezin; Kureha Chemical Industry Co Ltd, Tokyo, Japan) is an orally administered adsorbent showing adsorption ability superior to activated charcoal for certain organic compounds known to be precursors of substances that accumulate in patients with chronic kidney disease (CKD) and that are believed to accelerate the decline in kidney function. AST-120 is approved in Japan for prolonging time to hemodialysis therapy and improving uremic symptoms in patients with CKD. Methods: A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study was designed to examine the nephroprotective effects of 3 doses of AST-120 versus placebo in adult patients with moderate to severe CKD and elevated serum indoxyl sulfate levels while following an adequate protein-intake diet. Eligible patients were randomly assigned to 1 of 3 doses of AST-120 (0.9, 2.1, or 3.0 g) or placebo 3 times daily for 12 weeks. Results: AST-120 decreased serum indoxyl sulfate levels in a dose-dependent fashion. During the 12-week treatment period, AST-120 did not affect serum creatinine levels or 24-hour urine creatinine appearance. Significant improvements in malaise were observed in a dose-dependent fashion. All doses of AST-120 were well tolerated and did not adversely affect the general health status of patients. Conclusion: Results suggest that the dose of 3 g 3 times daily is an optimal dose for the US population, and it may be useful in the treatment of patients with CKD. Because AST-120 did not directly affect serum creatinine levels or 24-hour urine creatinine appearance, the composite end point of doubling of serum creatinine level, transplantation, and dialysis therapy would be appropriate for a confirmatory phase III therapeutic outcome study.

Original languageEnglish (US)
Pages (from-to)565-577
Number of pages13
JournalAmerican Journal of Kidney Diseases
Volume47
Issue number4
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Chronic Renal Insufficiency
Placebos
Creatinine
Indican
Serum
Japan
Urine
Therapeutics
AST 120
Chemical Industry
Tokyo
Charcoal
Health Status
Adsorption
Renal Dialysis
Dialysis
Transplantation
Outcome Assessment (Health Care)
Diet
Kidney

Keywords

  • AST-120
  • Chronic kidney disease (CKD)
  • Kremezin (Kureha Chemical Industry Co Ltd, Tokyo, Japan)
  • Nephroprotective
  • Serum creatinine
  • Serum indoxyl sulfate
  • Uremic toxins
  • Urine creatinine

ASJC Scopus subject areas

  • Nephrology

Cite this

A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD. / Schulman, Gerald; Agarwal, Rajiv; Acharya, Muralidhar; Berl, Tomas; Blumenthal, Samuel; Kopyt, Nelson.

In: American Journal of Kidney Diseases, Vol. 47, No. 4, 04.2006, p. 565-577.

Research output: Contribution to journalArticle

Schulman, Gerald ; Agarwal, Rajiv ; Acharya, Muralidhar ; Berl, Tomas ; Blumenthal, Samuel ; Kopyt, Nelson. / A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD. In: American Journal of Kidney Diseases. 2006 ; Vol. 47, No. 4. pp. 565-577.
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AU - Kopyt, Nelson

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