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


CONCLUSIONS
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.
Schulman
Gerald
G
Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA. gerald.schulman@vanderbilt.edu
Agarwal
Rajiv
R
Acharya
Muralidhar
M
Berl
Tomas
T
Blumenthal
Samuel
S
Kopyt
Nelson
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002244:Carbon / Q000008:administration & dosage*; D002908:Chronic Disease; D004311:Double-Blind Method; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D008875:Middle Aged; D010087:Oxides / Q000008:administration & dosage*; D012720:Severity of Illness Index
D010087:Oxides; D002244:Carbon; C040896:AST 120