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2)Duranton F, Cohen G, De Smet R, et al. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012; 23: 1258-70
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4)Niwa T, Ise M. Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med. 1994; 124: 96-104
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5)Niwa T, Ise M, Miyazaki T. Progression of glomerular sclerosis in experimental uremic rats by administration of indole, a precursor of indoxyl sulfate. Am J Nephrol. 1994; 14: 207-12
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6)Niwa T, Nomura T, Sugiyama S, et al. 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. 1997; 52: S23-8
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7)Miyazaki T, Ise M, Seo H, et al. Indoxyl sulfate increases the gene expressions of TGF-β1, TIMP-1 and proα(I) collagen in uremic rat kidneys. Kidney Int. 1997; 52: S15-22
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8)Enomoto A, Takeda M, Tojo A, et al. Role of organic anion transporters in the tubular transport of indoxyl sulfate and the induction of its nephrotoxicity. J Am Soc Nephrol. 2002; 13: 1711-20
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10)Owada S, Goto S, Bannai K, et al. Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats. Am J Nephrol. 2008; 28: 446-54
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11)Shimizu H, Bolati D, Adijiang A, et al. Senescence and dysfunction of proximal tubular cells are associated with activated p53 expression by indoxyl sulfate. Am J Physiol Cell Physiol. 2010; 299: C1110-7
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13)Bolati D, Shimizu H, Higashiyama Y, et al. Indoxyl sulfate induces epithelial-to-mesenchymal transition in rat kidneys and human proximal tubular cells. Am J Nephrol. 2011; 34: 318-23
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14)Shimizu H, Bolati D, Higashiyama Y, et al. Indoxyl sulfate upregulates renal expression of MCP-1 via production of ROS and activation of NF-κB, p53, ERK, and JNK in proximal tubular cells. Life Sci. 2012; 90: 525-30
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15)Shimizu H, Yisireyili M, Higashiyama Y, et al. Indoxyl sulfate upregulates renal expression of ICAM-1 via production of ROS and activation of NF-κB and p53 in proximal tubular cells. Life Sci. 2013; 92: 143-8
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16)Sun CY, Hsu HH, Wu MS. p-Cresol sulfate and indoxyl sulfate induce similar cellular inflammatory gene expressions in cultured proximal renal tubular cells. Nephrol Dial Transplant. 2013; 28: 70-8
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17)Shimizu H, Yisireyili M, Nishijima F, et al. Stat3 contributes to indoxyl sulfate-induced inflammatory and fibrotic gene expression and cellular senescence. Am J Nephrol. 2012; 36: 184-9
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18)Shimizu H, Yisireyili M, Nishijima F, et al. Indoxyl sulfate enhances p53-TGF-β1-Smad3 pathway in proximal tubular cells. Am J Nephrol. 2013; 37: 97-103
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19)Palm F, Nangaku M, Fasching A, et al. Uremia induces abnormal oxygen consumption in tubules and aggravates chronic hypoxia of the kidney via oxidative stress. Am J Physiol Renal Physiol. 2010; 299: F380-6
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20)Tanaka T, Yamaguchi J, Higashijima Y, et al. Indoxyl sulfate signals for rapid mRNA stabilization of Cbp/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2 (CITED2) and suppresses the expression of hypoxia-inducible genes in experimental CKD and uremia. FASEB J. 2013; 27: 4059-75
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21)Kawakami T, Inagi R, Wada T, et al. Indoxyl sulfate inhibits proliferation of human proximal tubular cells via endoplasmic reticulum stress. Am J Physiol Renal Physiol. 2010; 299: F568-76
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22)Chiang CK, Tanaka T, Inagi R, et al. Indoxyl sulfate, a representative uremic toxin, suppresses erythropoietin production in a HIF-dependent manner. Lab Invest. 2011; 91: 1564-71
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23)Adijiang A, Shimizu H, Higuchi Y, et al. Indoxyl sulfate reduces Klotho expression and promotes senescence in the kidneys of hypertensive rats. J Ren Nutr. 2011; 21: 105-9
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24)Shimizu H, Bolati D, Adijiang A, et al. Indoxyl sulfate downregulates renal expression of Klotho through production of ROS and activation of NF-κB. Am J Nephrol. 2011; 33: 319-24
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25)Sun CY, Chang SC, Wu MS. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 2012; 81: 640-50
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26)Shimizu H, Saito S, Higashiyama Y, et al. CREB, NF-κB, and NADPH oxidase coordinately upregulate indoxyl sulfate-induced angiotensinogen expression in proximal tubular cells. Am J Physiol Cell Physiol. 2013: 304: C685-92
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27)Sun CY, Chang SC, Wu MS. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS One. 2012; 7: e34026
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28)Akiyama Y, Kikuchi K, Saigusa D, et al. Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3. PLoS One. 2013; 8: e66518
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29)Sun CY, Young GH, Hsieh YT, et al. Protein-bound uremic toxins induce tissue remodeling by targeting the EGF receptor. J Am Soc Nephrol. 2014; pii: ASN.2014010021. [Epub ahead of print]
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30)Takayama F, Taki K, Niwa T. Bifidobacterium in gastro-resistant seamless capsule reduces serum levels of indoxyl sulfate in patients on hemodialysis. Am J Kidney Dis. 2003; 41(3 Suppl 1): S142-5
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31)Furuse SU, Ohse T, Jo-Watanabe A, et al. Galacto-oligosaccharides attenuate renal injury with microbiota modification. Physiol Rep. 2014; 2. pii: e12029
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32)Saito H, Yoshimura M, Saigo C, et al. Hepatic sulfotransferase as a nephropreventing target by suppression of the uremic toxin indoxyl sulfate accumulation in ischemic acute kidney injury. Toxicol Sci. 2014; 141: 206-17
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33)Niwa T. Indoxyl sulfate is a nephro-vascular toxin. J Ren Nutr. 2010; 20(Suppl 1): S2-6
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34)Adijiang A, Goto S, Uramoto S, et al. Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats. Nephrol Dial Transplant. 2008; 23: 1892-901
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35)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. Nephrol Dial Transplant. 2009; 24: 2051-8
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36)Muteliefu G, Enomoto A, Niwa T. Indoxyl sulfate promotes proliferation of human aortic smooth muscle cells by inducing oxidative stress. J Ren Nutr. 2009; 19: 29-32
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37)Muteliefu G, Shimizu H, Enomoto A, et al. Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21 and prelamin A through oxidative stress. Am J Physiol Cell Physiol. 2012; 303: C126-34
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38)Yamamoto H, Tsuruoka S, Ioka T, et al. Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells. Kidney Int. 2006; 69: 1780-5
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39)Chitalia VC, Shivanna S, Martorell J, et al. Uremic serum and solutes increase post-vascular interventional thrombotic risk through altered stability of smooth muscle cell tissue factor. Circulation. 2013; 127: 365-76
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40)Dou L, Bertrand E, Cerini C, et al. The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair. Kidney Int. 2004; 65: 442-51
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41)Tumur Z, Niwa T. Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells. Am J Nephrol. 2009; 29: 551-7
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42)Dou L, Jourde-Chiche N, Faure V, et al. The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells. J Thromb Haemost. 2007; 5: 1302-8
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43)Yu M, Kim YJ, Kang DH. Indoxyl sulfate-induced endothelial dysfunction in patients with chronic kidney disease via an induction of oxidative stress. Clin J Am Soc Nephrol. 2011; 6: 30-9
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44)Tumur Z, Shimizu H, Enomoto A, et al. Indoxyl sulfate upregulates expression of ICAM-1 and MCP-1 by oxidative stress-induced NF-κB activation. Am J Nephrol. 2010; 31: 435-41
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45)Ito S, Osaka M, Higuchi Y, et al. Indoxyl sulfate induces leukocyte-endothelial interactions through up-regulation of E-selectin. J Biol Chem. 2010; 285: 38869-75
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46)Adelibieke Y, Shimizu H, Muteliefu G, et al. Indoxyl sulfate induces endothelial cell senescence by increasing reactive oxygen species production and p53 activity. J Ren Nutr. 2012; 22: 86-9
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47)Faure V, Dou L, Sabatier F, et al. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost. 2006; 4: 566-73
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48)Itoh Y, Ezawa A, Kikuchi K, et al. Protein-bound uremic toxins in hemodialysis patients measured by liquid chromatography/tandem mass spectrometry and their effects on endothelial ROS production. Anal Bioanal Chem. 2012; 403: 1841-50
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49)Lekawanvijit S, Adrahtas A, Kelly DJ, et al. Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes? Eur Heart J. 2010; 31: 1771-9
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50)Yisireyili M, Shimizu H, Saito S, et al. Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats. Life Sci. 2013; 92: 1180-5
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51)Fujii H, Nishijima F, Goto S, et al. Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress. Nephrol Dial Transplant. 2009; 24: 2089-95
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52)Niwa T, Shimizu H. Indoxyl sulfate induces nephrovascular senescence. J Ren Nutr. 2012; 22: 102-6
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53)Schroeder JC, Dinatale BC, Murray IA, et al. The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry. 2010; 49: 393-400
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54)Barreto FC, Barreto DV, Liabeuf S, et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009; 4: 1551-8
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55)Sato B, Yoshikawa D, Ishii H, et al. Indoxyl sulfate, a uremic toxin, and carotid intima-media thickness in patients with coronary artery disease. Int J Cardiol. 2013; 163: 214-6
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56)Shimazu S, Hirashiki A, Okumura T, et al. Association between indoxyl sulfate and cardiac dysfunction and prognosis in patients with dilated cardiomyopathy. Circ J. 2013; 77: 390-6
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57)Nii-Kono T, Iwasaki Y, Uchida M, et al. Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells. Kidney Int. 2007; 71: 738-43
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59)Kim YH, Kwak KA, Gil HW, et al. Indoxyl sulfate promotes apoptosis in cultured osteoblast cells. BMC Pharmacol Toxicol. 2013; 14: 60
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60)Mozar A, Louvet L, Godin C, et al. Indoxyl sulphate inhibits osteoclast differentiation and function. Nephrol Dial Transplant. 2012; 27: 2176-81
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65)Meijers BK, De Loor H, Bammens B, et al. p-Cresyl sulfate and indoxyl sulfate in hemodialysis patients. Clin J Am Soc Nephrol. 2009; 4: 1932-8
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66)Wu IW, Hsu KH, Hsu HJ, et al. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortarity in elderly hemodialysis patients-a prospective cohort study. Nephrol Dial Transplant. 2012; 27: 1169-75
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67)Poesen R, Viaene L, Verbeke K, et al. Cardiovascular disease relates to intestinal uptake of p-cresol in patients with chronic kidney disease. BMC Nephrol. 2014; 15: 87
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68)Watanabe H, Miyamoto Y, Honda D, et al. p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int. 2013; 83: 582-92
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69)Koppe L, Pillon NJ, Vella RE, et al. p-Cresyl sulfate promotes insulin resistance associated with CKD. J Am Soc Nephrol. 2013; 24: 88-99
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