Carbonic-adsorbent AST-120 reduces overload of indoxyl sulfate and the plasma level of TGF-beta1 in patients with chronic renal failure.
BACKGROUND
We previously reported a significant increase in plasma TGF-beta1 in patients with chronic renal failure (CRF). Progression of CRF may be caused by persistent renal production of TGF-beta1. In CRF rat models, an oral carbonic absorbent (AST-120) reduces the expression of the TGF-beta1 gene in the kidney, and delays the progression of CRF, in part by alleviating the overload of indoxyl sulfate. The aim of this study was to evaluate the effect of AST-120 on plasma levels of indoxyl sulfate and TGF-beta1 in CRF patients.


METHODS
Ten CRF patients (aged 59.3 +/- 9.5 years, 5 men, serum creatinine 4.37 +/- 1.72 mg/dl) were enrolled in this study. All patients maintained a regular dietary therapy and the same medication throughout the study. AST-120 was added at a dose of 6 g/day. Parameters including the slope of the reciprocal of the serum creatinine-time plot, plasma indoxyl sulfate level, and plasma and urinary levels of TGF-beta1 were compared before and after the treatment with AST-120. The mean observation periods before and after the treatment were 9.7 +/- 2.8 and 6.5 +/- 2.9 months, respectively.


RESULTS
Administration of AST-120 significantly reduced the plasma levels of indoxyl sulfate (1.42 +/- 1.50 vs. 1.26 +/- 1.40 mg/dl, P < 0.05) and TGF-beta1 (17.9 +/- 7.2 vs. 10.6 +/- 4.7 ng/ml, P < 0.05) and improved the slope of the reciprocal of serum creatinine (-0.061 +/- 0.041 vs. -0.032 +/- 0.055 dl/mg/year, P < 0.05).


CONCLUSIONS
These results support the notion that indoxyl sulfate and TGF-beta1 may be involved in the progression of CRF, and that the oral adsorbent AST-120 may suppress the progression, at least in part, by reducing overproduction of TGF-beta1.
Iida
Shuji
S
Department of Nephrology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Kohno
Keisuke
K
Yoshimura
Junko
J
Ueda
Seiji
S
Usui
Michiaki
M
Miyazaki
Hiroshi
H
Nishida
Hidemi
H
Tamaki
Kiyoshi
K
Okuda
Seiya
S
D000327:Adsorption; D000368:Aged; D002244:Carbon / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007200:Indican / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010087:Oxides / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000097:blood* / Q000652:urine
D010087:Oxides; D053773:Transforming Growth Factor beta1; D002244:Carbon; C040896:AST 120; D007200:Indican