Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation

被引:50
作者
Nakamura, Tsukasa [2 ]
Sato, Eiichi [2 ]
Fujiwara, Nobuharu [2 ]
Kawagoe, Yasuhiro [2 ]
Suzuki, Tsukasa [3 ]
Ueda, Yoshihiko [3 ]
Yamagishi, Sho-ichi [1 ]
机构
[1] Kurume Univ, Sch Med, Dept Pathophysiol & Therapeut Diabet Vasc Complic, Fukuoka 8300011, Japan
[2] Shinmatsudo Cent Gen Hosp, Dept Internal Med, Div Nephrol, Chiba 1700034, Japan
[3] Dokkyo Univ, Sch Med, Koshigaya Hosp, Dept Pathol, Saitama 3438555, Japan
来源
METABOLISM-CLINICAL AND EXPERIMENTAL | 2011年 / 60卷 / 02期
关键词
CHRONIC KIDNEY-DISEASE; ACID-BINDING PROTEIN; DIABETIC-NEPHROPATHY; URINARY-EXCRETION; INDOXYL SULFATE; UREMIC RATS; AGES; PROGRESSION; EXPRESSION; CELLS;
D O I
10.1016/j.metabol.2010.01.023
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
AST-120 is an oral adsorbent that attenuates the progression of chronic renal failure (CRF) and improves the prognosis of the patients under dialysis. Although tubulointerstitial injury is more important than glomerulopathy in terms of renal prognosis in patients with CRF, effect of AST-120 on tubular injury in CRF patients remains unknown. In this study, we examined whether and how AST-120 treatment could improve tubular damage in nondiabetic CRF patients. Fifty nondiabetic CRF patients were enrolled in the present study and divided into 2 groups: one was the AST-120 treated group (15 men and 10 women) and the other was the age-, sex-, and clinical variables matched non-AST-120-treated control group. Patients were followed up for 12 months. We investigated the effects of AST-120 on serum levels of interleukin-6 (IL-6), proteinuria, and urinary excretion levels of 8-hydroxydeoxyguanosine (8-OHdG) and L-fatty acid binding protein (L-FABP), markers of oxidative stress and tubular injury, respectively. AST-120 treatment (6 g/d), but not control treatment, for 12 months significantly reduced IL-6, proteinuria, and urinary excretion levels of L-FABP and 8-OHdG, and inhibited the increase in serum creatinine in CRF patients. In univariate analyses, L-FABP levels were correlated with age, proteinuria, 8-OHdG, and IL-6. In multiple stepwise regression analysis, proteinuria and urinary 8-OHdG levels were independently related to L-FABP levels (R-2 = 0.605). Our present study demonstrated for the first time that AST-120 improved tubular injury in nondiabetic CRF patients. AST-120 may exert beneficial effects in CRF patients by protecting tubular damage partly via reduction of proteinuria and oxidative stress generation. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:260 / 264
页数:5
相关论文
共 28 条
[1]
[Anonymous], KIDNEY INT S
[2]
The role of proteinuria in the progression of chronic renal failure [J].
Burton, C ;
Harris, KPG .
AMERICAN JOURNAL OF KIDNEY DISEASES, 1996, 27 (06) :765-775
[3]
Pathophysiology of proteinuria [J].
D'Amico, G ;
Bazzi, C .
KIDNEY INTERNATIONAL, 2003, 63 (03) :809-825
[4]
Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts [J].
Djamali, Arjang .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2007, 293 (02) :F445-F455
[5]
Role of AGEs in diabetic nephropathy [J].
Fukami, Kei ;
Yamagishi, Sho-ichi ;
Ueda, Seiji ;
Okuda, Seiya .
CURRENT PHARMACEUTICAL DESIGN, 2008, 14 (10) :946-952
[6]
Increased excretion of N-acetyl-β-D-glucosaminidase and β2-microglobulin in gestational week 30 [J].
Hayashi, M ;
Tomobe, K ;
Hirabayashi, H ;
Hoshimoto, K ;
Ohkura, T ;
Inaba, N .
AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2001, 321 (03) :168-172
[7]
Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease [J].
Imai E. ;
Horio M. ;
Nitta K. ;
Yamagata K. ;
Iseki K. ;
Hara S. ;
Ura N. ;
Kiyohara Y. ;
Hirakata H. ;
Watanabe T. ;
Moriyama T. ;
Ando Y. ;
Inaguma D. ;
Narita I. ;
Iso H. ;
Wakai K. ;
Yasuda Y. ;
Tsukamoto Y. ;
Ito S. ;
Makino H. ;
Hishida A. ;
Matsuo S. .
Clinical and Experimental Nephrology, 2007, 11 (1) :41-50
[8]
Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein as a marker for the monitoring of chronic kidney disease: A multicenter trial [J].
Kamijo, A ;
Sugaya, T ;
Hikawa, A ;
Yamanouchi, M ;
Hirata, Y ;
Ishimitsu, T ;
Numabe, A ;
Takagi, M ;
Hayakawa, H ;
Tabei, F ;
Sugimoto, T ;
Mise, N ;
Kimura, K .
JOURNAL OF LABORATORY AND CLINICAL MEDICINE, 2005, 145 (03) :125-133
[9]
AST-120 (Kremezin®) initiated in early stage chronic kidney disease stunts the progression of renal dysfunction in type 2 diabetic subjects [J].
Konishi, Kazunori ;
Nakano, Shigeru ;
Tsuda, Shin-ichi ;
Nakagawa, Atsushi ;
Kigoshi, Toshikazu ;
Koya, Daisuke .
DIABETES RESEARCH AND CLINICAL PRACTICE, 2008, 81 (03) :310-315
[10]
Irbesartan inhibits advanced glycation end product (AGE)-induced proximal tubular cell injury in vitro by suppressing receptor for AGEs (RAGE) expression [J].
Matsui, Takanori ;
Yamagishi, Sho-ichi ;
Takeuchi, Masayoshi ;
Ueda, Seiji ;
Fukami, Kei ;
Okuda, Seiya .
PHARMACOLOGICAL RESEARCH, 2010, 61 (01) :34-39