切换至 "中华医学电子期刊资源库"

中华肾病研究电子杂志 ›› 2017, Vol. 06 ›› Issue (06) : 284 -288. doi: 10.3877/cma.j.issn.2095-3216.2017.06.008

所属专题: 文献

综述

硫酸吲哚酚清除方式的研究进展
刘书馨1,(), 梅芳芳2   
  1. 1. 116033 大连市中心医院
    2. 116033 大连市中心医院;116044 大连医科大学
  • 收稿日期:2017-10-24 出版日期:2017-12-28
  • 通信作者: 刘书馨
  • 基金资助:
    辽宁省自然基金(201602219)

Progress of research on the clearance of indoxyl sulfate

Shuxin Liu1,(), Fangfang Mei2   

  1. 1. Department of Nephrology, Dalian Central Hospital, Dalian 116033, Liaoning Province, China
    2. Department of Nephrology, Dalian Central Hospital, Dalian 116033, Liaoning Province, China; Dalian Medical University, Dalian 116044, Liaoning Province, China
  • Received:2017-10-24 Published:2017-12-28
  • Corresponding author: Shuxin Liu
  • About author:
    Corresponding author: Liu Shuxin, Email:
引用本文:

刘书馨, 梅芳芳. 硫酸吲哚酚清除方式的研究进展[J]. 中华肾病研究电子杂志, 2017, 06(06): 284-288.

Shuxin Liu, Fangfang Mei. Progress of research on the clearance of indoxyl sulfate[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2017, 06(06): 284-288.

硫酸吲哚酚(IS)是一种尿毒症毒素,由肠道微生物分解色氨酸产生,它是小分子溶质,但是与血浆蛋白结合率高达90%以上。肾功能正常时,通过肾小管分泌作用排出体外。肾功能受损时,在体内蓄积,因此慢性肾脏病(CKD)患者血浆IS水平升高。IS具有肾毒性,可以导致肾间质纤维化和肾小球硬化,加速CKD的进展;同时具有心血管毒性,导致心肌纤维化和左室肥厚等造成心血管系统损害。心血管疾病被公认为是CKD患者死亡的主要原因。研究发现,IS可以增加终末期肾病(ESRD)患者全因死亡及心血管疾病死亡的风险。因此通过透析或非透析的方式降低血浆IS水平非常重要。本文将针对近年来国内外学者关于IS清除的研究成果进行归纳总结。

Indoxyl sulfate (IS) is a uremic toxin that is a small molecule solute, as many as 90% of which bind to the plasma proteins. IS derives from the breakdown of tryptophan by gut microbes. Normal renal function can lead to IS excretion through the tubular secretion, while impaired renal function can result in accumulation of IS in the body. So plasma IS levels are elevated in patients with chronic kidney disease (CKD). IS has nephrotoxicity, and can cause renal interstitial fibrosis and glomerulosclerosis, accelerating the progression of CKD. IS also has cardiovascular toxicity, leading to myocardial fibrosis and left ventricular hypertrophy, etc. Cardiovascular disease has been widely recognized as the leading cause of death in CKD patients. Studies have found that IS can increase the risk of all-cause death and cardiovascular death in patients with end-stage renal disease (ESRD). Therefore, it is very important to reduce plasma IS level by means of dialysis or non-dialysis method. This article summarized the research results on IS clearance by domestic and foreign scholars in recent years.

1
Lin CJ, Liu HL, Pan CF, et al. Indoxyl sulfate predicts cardiovascular disease and renal function deterioration in advanced chronic kidney disease [J]. Arch Med Res, 2012, 43(6): 451-456.
2
Barreto FC, Barreto DV, Liabeuf S, et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients [J]. Clin J Am Soc Nephrol, 2009, 4(10): 1551-1558.
3
高卓,魏日胞,陈香美. 硫酸吲哚酚,炎症因子与肾脏纤维化[J]. 临床肾脏病杂志,2007, 7(4): 187-188.
4
Aoyama I, Niwa T. Molecular insights into preventive effects of AST-120 on the progression of renal failure [J]. Clin Exp Nephrol, 2001, 5(4): 209-216.
5
Komiya T, Miura K, Tsukamoto J, et al. Possible involvement of nuclear factor-κB inhibition in the renal protective effect of oral adsorbent AST-120 in a rat model of chronic renal failure [J]. Int J Mol Med, 2004, 13(1): 133-138.
6
Tumur Z, Niwa T. Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells [J]. Am J Nephrology, 2009, 29(6): 551-557.
7
Shimizu H, Hirose Y, Goto S, et al. Indoxyl sulfate enhances angiotensin II signaling through upregulation of epidermal growth factor receptor expression in vascular smooth muscle cells [J]. Life Sci, 2012, 91(5): 172-177.
8
Adijiang A, Goto S, Uramoto S, et al. Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats [J]. Nephrol Dial Transplant, 2008, 23(6): 1892-1901.
9
Muteliefu G, Enomoto A, Jiang P, et al. Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells [J]. Nephrol Dial Transplant, 2009, 24(7): 2051-2058.
10
Yisireyili M, Shimizu H, Saito S, et al. Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats [J]. Life Sci, 2013, 92(24): 1180-1185.
11
Lekawanvijit S, Adrahtas A, Kelly DJ, et al. Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? [J]. Eur Heart J, 2010, 31(14): 1771-1779.
12
Sirich TL, Aronov PA, Plummer NS, et al. Numerous protein-bound solutes are cleared by the kidney with high efficiency [J]. Kidney Int, 2013, 84(3): 585-590.
13
Nigam SK, Wu W, Bush KT, et al. Handling of drugs, metabolites, and uremic toxins by kidney proximal tubule drug transporters [J]. Clin J Am Soc Nephrol, 2015, 10(11): 2039-2049.
14
Deguchi T, Ohtsuki S, Otagiri M, et al. Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney [J]. Kidney Int, 2002, 61(5): 1760-1768.
15
Wikoff WR, Nagle MA, Kouznetsova VL, et al. Untargeted metabolomics identifies enterobiome metabolites and putative uremic toxins as substrates of organic anion transporter 1 (Oat1) [J]. J Proteome Res, 2011, 10(6): 2842-2851.
16
Yu CP, Sweet DH, Peng YH, et al. Effects of nonsteroidal anti-inflammatory drugs on the renal excretion of indoxyl sulfate, a nephro-cardiovascular toxin, in rats [J]. Eur J Pharm Sci, 2017, 101: 66-70.
17
Martinez AW, Recht NS, Hostetter TH, et al. Removal of p-cresol sulfate by hemodialysis [J]. J Am Soc Nephrol, 2005, 16(11): 3430-3436.
18
Eloot S, Schneditz D, Cornelis T, et al. Protein-bound uremic toxin profiling as a tool to optimize hemodialysis [J]. PLoS One, 2016, 11(1): e0147159.
19
Luo FJG, Patel KP, Marquez IO, et al. Effect of increasing dialyzer mass transfer area coefficient and dialysate flow on clearance of protein-bound solutes: a pilot crossover trial [J]. Am J Kidney Dis, 2009, 53(6): 1042-1049.
20
Marquez IO, Tambra S, Luo FY, et al. Contribution of residual function to removal of protein-bound solutes in hemodialysis [J]. Clin J Am Soc Nephrol, 2011, 6(2): 290-296.
21
Pham NM, Recht NS, Hostetter TH, et al. Removal of the protein-bound solutes indican and p-cresol sulfate by peritoneal dialysis [J]. Clin J Am Soc Nephrol, 2008, 3(1): 85-90.
22
Sirich TL, Funk BA, Plummer NS, et al. Prominent accumulation in hemodialysis patients of solutes normally cleared by tubular secretion [J]. J Am Soc Nephrol, 2014, 25(3): 615-622.
23
Poesen R, Mutsaers HAM, Windey K, et al. The influence of dietary protein intake on mammalian tryptophan and phenolic metabolites [J]. PLoS One, 2015, 10(10): e0140820.
24
Patel KP, Luo FJG, Plummer NS, et al. The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores [J]. Clin J Am Soc Nephrol, 2012, 7(6): 982-988.
25
Sirich TL. Dietary protein and fiber in end stage renal disease [J]. Semin Dial, 2015, 28(1):75-80.
26
Schreiner GE. The search for the uremic toxin(s) [J]. Kidney Int, 1975, Suppl(3): 270-271.
27
Marzocco S, Dal Piaz F, Di Micco L, et al. Very low protein diet reduces indoxyl sulfate levels in chronic kidney disease [J]. Blood Purif, 2013, 35(1-3): 196-201.
28
Poesen R, Evenepoel P, de Loor H, et al. The influence of prebiotic arabinoxylan oligosaccharides on microbiota derived uremic retention solutes in patients with chronic kidney disease: A randomized controlled trial [J]. PLoS One, 2016, 11(4): e0153893.
29
Meijers BKI, De Preter V, Verbeke K, et al. p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin [J]. Nephrol Dial Transplant, 2009, 25(1): 219-224.
30
Sirich TL, Plummer NS, Gardner CD, et al. Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients [J]. Clin J Am Soc Nephrol, 2014, 9(9): 1603-1610.
31
Takayama F, Taki K, Niwa T. Bifidobacterium in gastro-resistant seamless capsule reduces serum levels of indoxyl sulfate in patients on hemodialysis [J]. Am J Kidney Dis, 2003, 41(3): S142-S145.
32
Fang CY, Lu JR, Chen BJ, et al. Selection of uremic toxin-reducing probiotics in vitro and in vivo [J]. J Funct Foods, 2014, 7: 407-415.
33
Rossi M, Johnson DW, Morrison M, et al. Synbiotics easing renal failure by improving gut microbiology (SYNERGY): a randomized trial [J]. Clin J Am Soc Nephrol, 2016, 11(2): 223-231.
34
Lekawanvijit S, Kompa AR, Manabe M, et al. Chronic kidney disease-induced cardiac fibrosis is ameliorated by reducing circulating levels of a non-dialysable uremic toxin, indoxyl sulfate [J]. PLoS One, 2012, 7(7): e41281.
35
Maeda K, Hamada C, Hayashi T, et al. Long-term effects of the oral adsorbent, AST-120, in patients with chronic renal failure [J]. J Int Med Res, 2009, 37(1): 205-213.
36
Ueda H, Shibahara N, Takagi S, et al. AST-120 treatment in pre-dialysis period affects the prognosis in patients on hemodialysis [J]. Ren Fail, 2008, 30(9): 856-860.
37
Hatakeyama S, Yamamoto H, Okamoto A, et al. Effect of an oral adsorbent, AST-120, on dialysis initiation and survival in patients with chronic kidney disease [J]. Int J Nephrol, 2012, 2012: 376128.
38
Schulman G, Agarwal R, Acharya M, et al. A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD [J]. Am J Kidney Dis, 2006, 47(4): 565-577.
39
Schulman G, Berl T, Beck GJ, et al. Randomized placebo-controlled EPPIC trials of AST-120 in CKD [J]. J Am Soc Nephrol, 2015, 26(7): 1732-1746.
40
Cha R, Kang SW, Park CW, et al. A randomized, controlled trial of oral intestinal sorbent AST-120 on renal function deterioration in patients with advanced renal dysfunction [J]. Clin J Am Soc Nephrol, 2016, 11(4): 559-567.
41
Anraku M, Tabuchi R, Ifuku S, et al. An oral absorbent, surface-deacetylated chitin nano-fiber ameliorates renal injury and oxidative stress in 5/6 nephrectomized rats [J]. Carbohydr Polym, 2017, 161: 21-25.
42
初启江. 血液透析对硫酸吲哚酚清除效果研究[J]. 国际移植与血液净化杂志,2009, 7(2): 30-31.
43
张宏,李新伦,伦立德. 不同血液净化模式对维持性血液透析患者蛋白结合类毒素的清除效果[J]. 肾脏病与透析肾移植杂志,2016, 25(5):425-430.
44
Abad S, Vega A, Quiroga B, et al. Protein-bound toxins: added value in their removal with high convective volumes [J]. Nefrología, 2016, 36(6): 637-642.
45
Meyer TW, Peattie JWT, Miller JD, et al. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate [J]. J Am Soc Nephrol, 2007, 18(3): 868-874.
46
Camacho O, Rosales MC, Shafi T, et al. Effect of a sustained difference in hemodialytic clearance on the plasma levels of p-cresol sulfate and indoxyl sulfate [J]. Nephrol Dial Transplant, 2016, 31(8): 1335-1341.
47
Eloot S, Schneditz D, Cornelis T, et al. Protein-bound uremic toxin profiling as a tool to optimize hemodialysis [J]. PLoS One, 2016, 11(1): e0147159.
48
Tao X, Thijssen S, Levin N, et al. Enhanced indoxyl sulfate dialyzer clearance with the use of binding competitors [J]. Blood Purif, 2015, 39(4): 323-330.
49
Tijink MSL, Wester M, Glorieux G, et al. Mixed matrix hollow fiber membranes for removal of protein-bound toxins from human plasma [J]. Biomaterials, 2013, 34(32): 7819-7828.
50
冷伟,陈明霞,赵钰荣,等. 涤毒灌肠方对5/6肾切除大鼠血与尿硫酸吲哚酚含量的影响[J]. 广东药学院学报,2014,29(6): 762-765.
51
郑艳辉,孔薇,张丽香,等. 中药结肠透析对慢性肾脏病人蛋白结合型毒素清除的影响[J]. 贵阳中医学院学报,2014, 36(2): 27-29.
[1] 李琛, 张惟佳, 潘亚萍. 牙周炎与系统性疾病之间关系的应用思考:2022年EFP和WONCA欧洲分部联合研讨会共识报告的解读及启示[J]. 中华口腔医学研究杂志(电子版), 2023, 17(05): 322-327.
[2] 周川鹏, 杨浩, 魏微阳, 王奇, 黄亚强. 微创与标准通道经皮肾镜治疗肾结石合并肾功能不全的对比研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 470-475.
[3] 杨聚荣. 透析患者妊娠的管理[J]. 中华肾病研究电子杂志, 2023, 12(05): 300-300.
[4] 杨静, 顾红叶, 赵莹莹, 孙梦霞, 查园园, 王琪. 老年血液透析患者短期死亡的影响因素及列线图预测模型的预测作用[J]. 中华肾病研究电子杂志, 2023, 12(05): 254-259.
[5] 程庆砾. 新冠病毒感染与肾脏[J]. 中华肾病研究电子杂志, 2023, 12(04): 240-240.
[6] 罗阳燕, 王少清, 高芳, 沈艳, 张万军, 李莉. 尿毒清颗粒对腹膜透析患者残余肾功能及腹透液纤连蛋白和TGF-β1水平的作用[J]. 中华肾病研究电子杂志, 2023, 12(04): 200-204.
[7] 李思佳, 苏晓乐, 王利华. 通过抑制Wnt/β-catenin信号通路延缓肾间质纤维化研究进展[J]. 中华肾病研究电子杂志, 2023, 12(04): 224-228.
[8] 杨长沅, 凌曦淘, 丘伽美, 段若兰, 李琴, 林玉婕, 秦新东, 侯海晶, 卢富华, 苏国彬. 慢性肾脏病患者衰弱的筛查/评估工具研究进展[J]. 中华肾病研究电子杂志, 2023, 12(04): 229-233.
[9] 金艳盛, 董改琴, 李晓忠. 巨噬细胞在慢性肾脏病患者血管钙化中的作用与机制研究进展[J]. 中华肾病研究电子杂志, 2023, 12(04): 234-237.
[10] 易成, 韦伟, 赵宇亮. 急性肾脏病的概念沿革[J]. 中华临床医师杂志(电子版), 2023, 17(08): 906-910.
[11] 周加军, 余永武, 周涵, 张凌. 358例继发性甲状旁腺功能亢进症患者异位甲状旁腺的检出及分布情况分析[J]. 中华临床医师杂志(电子版), 2023, 17(04): 381-385.
[12] 张赟辉, 罗军, 刘栗丽, 汪宏, 耿克明. 腹膜透析与血液透析对老年终末期肾病患者营养状况及炎症反应的影响[J]. 中华临床医师杂志(电子版), 2023, 17(04): 419-423.
[13] 郑景达, 黄金旗, 张庆贤, 陈煌, 高晓杰. 小腿深静脉入路AngioJet一站式血栓清除治疗全肢型急性下肢深静脉血栓形成患者的临床研究[J]. 中华介入放射学电子杂志, 2023, 11(04): 305-309.
[14] 张天, 余京华, 王攀登, 郭晨凡, 刘涛. 一例使用异物抓捕器治疗导管纤维蛋白鞘的病例报告[J]. 中华介入放射学电子杂志, 2023, 11(03): 284-286.
[15] 白明悦, 杨淑娜, 胡红梅, 胡文立. 透析患者脑小血管病患病情况的研究现状及其机制探讨[J]. 中华脑血管病杂志(电子版), 2023, 17(05): 505-509.
阅读次数
全文


摘要