Carbonic-adsorbent AST-120 reduces overload of indoxyl sulfate and the plasma level of TGF-β1 in patients with chronic renal failure

被引：31

作者：

Iida S. ^{[1
]}

Kohno K. ^{[1
]}

Yoshimura J. ^{[1
]}

Ueda S. ^{[1
]}

Usui M. ^{[1
]}

Miyazaki H. ^{[1
]}

Nishida H. ^{[1
]}

Tamaki K. ^{[1
]}

Okuda S. ^{[1
]}

机构：

[1] Department of Nephrology, Kurume University, School of Medicine, Kurume

来源：

Clinical and Experimental Nephrology | 2006年 / 10卷 / 4期

关键词：

AST-120; Indoxyl sulfate; Oral adsorbent; Proteinuria; Renal failure; Transforming growth factor-β1;

D O I：

10.1007/s10157-006-0441-8

中图分类号：

学科分类号：

摘要：

Background. We previously reported a significant increase in plasma TGF-β1 in patients with chronic renal failure (CRF). Progression of CRF may be caused by persistent renal production of TGF-β1. In CRF rat models, an oral carbonic absorbent (AST-120) reduces the expression of the TGF-β1 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-β1 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-β1 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-β1 (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-β1 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-β1. © 2006 Japanese Society of Nephrology.

引用

页码：262 / 267

页数：5

共 26 条

[1]

Niwa T., Nomura T., Sugiyama S., Miyazaki T., Tsukushi S., Tsutsui S., The protein metabolite hypothesis, a model for the progression of renal failure: An oral adsorbent lowers indoxyl sulfate levels in undialyzed uremic patients, Kidney Int, 62, pp. 23-8, (1997)

[2]

Sanaka T., Fujimoto K., Niwayama J., Naito T., Higuchi C., Akizawa T., Et al., Effect of combined treatment of oral sorbent with protein-restricted diet on change of reciprocal creatinine slope in patients with CRF, Am J Kidney Dis, 4, pp. 35-7, (2003)

[3]

Tsubakihara Y., Takabatake Y., Oka K., Shoji T., Okada N., Takahito I., Et al., Effects of the oral adsorbent AST-120 on tryptophan metabolism in uremic patients, Am J Kidney Dis, 41, pp. 38-41, (2003)

[4]

Yorioka N., Ito T., Masaki T., Ogata S., Asakimori Y., Tanji C., Et al., Dose-dependent effect of an oral adsorbent, AST-120, in patients with early chronic renal failure, J Int Med Res, 30, pp. 467-75, (2002)

[5]

Miyazaki T., Aoyama I., Ise M., Seo H., Niwa T., An oral sorbent reduces overload of indoxyl sulphate and gene expression of TGF-beta1 in uraemic rat kidneys, Nephrol Dial Transplant, 15, pp. 1773-81, (2000)

[6]

Border W.A., Ruoslahit E., Transforming growth factor-β1 in disease: The dark side of tissue repair, J Clin Invest, 90, pp. 1-7, (1992)

[7]

Border W.A., Okuda S., Languino L.R., Ruoslahti E., Transforming growth factor-β1 regulates production of proteoglycans by mesangial cells, Kidney Int, 37, pp. 689-95, (1990)

[8]

Okuda S., Languino L.R., Ruoslahti E., Border W.A., Elevated expression of transforming growth factor-β and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix, J Clin Invest, 86, pp. 453-62, (1990)

[9]

Tamaki K., Okuda S., Ando T., Iwamoto T., Nakayama M., Fujishima M., TGF-β1 in glomerulosclerosis and interstitial fibrosis of adriamycin nephropathy, Kidney Int, 45, pp. 525-36, (1994)

[10]

Tamaki K., Okuda S., Nakayama M., Yanagida T., Fujishima M., Transforming growth factor-β1 in hypertensive renal injury in Dahl salt-sensitive rats, J Am Soc Nephrol, 7, pp. 2578-89, (1996)

← 1 2 3 →