Protein-Bound Molecules: A Large Family With a Bad Character

Seminars in Nephrology

Volumn 34, Issue 2, 2014, Pages 106-117

  Sirich, Tammy L ^a   Meyer, Timothy W ^a   Gondouin, Bertrand ^b,c   Brunet, Philippe ^b,c   Niwa, Toshimitsu ^d  

^a STANFORD UNIVERSITY   (United States)

^b INSERM   (France)

^c ASSISTANCE PUBLIQUE HÔPITAUX DE MARSEILLE   (France)

^d NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Protein bound; Renal dialysis; Uremia

Indexed keywords

FUNCTIONAL GROUP; INDICAN; P CRESYL SULFATE; UNCLASSIFIED DRUG; UREMIC TOXIN; 4-CRESOL SULFATE; CRESOL; PROTEIN BINDING; SULFATE;

BIOACCUMULATION; BONE MALFORMATION; CARDIOVASCULAR DISEASE; CHRONIC KIDNEY DISEASE; COGNITIVE DEFECT; DISEASE COURSE; HUMAN; KIDNEY TUBULE EXCRETION; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN BINDING; RENAL REPLACEMENT THERAPY; REVIEW; UREMIA; CARDIOVASCULAR DISEASES; COGNITION DISORDERS; KIDNEY DISEASES; METABOLISM;

CARDIOVASCULAR DISEASES; COGNITION DISORDERS; CRESOLS; HUMANS; INDICAN; KIDNEY DISEASES; PROTEIN BINDING; SULFURIC ACID ESTERS;

EID: 84899113391     PISSN: 02709295     EISSN: 15584488     Source Type: Journal    
DOI: 10.1016/j.semnephrol.2014.02.004     Document Type: Review

References (125)

1. Schmidt S., Gonzalez D., Derendorf H. Significance of protein binding in pharmacokinetics and pharmacodynamics. J Pharm Sci 2010, 99:1107-1122.
2. Marshall E.K. Two lectures on renal physiology. Physiologist 1966, 9:367-384.
3. Masereeuw R., Mutsaers H.A.M., Toyohara T., Abe T., Jhawar S., Sweet D.H., et al. The kidney and uremic toxin removal: glomerulus or tubulus?. Semin Nephrol 2014, 34:191-208.
4. Vanholder R., De Smet R., Glorieux G., Argiles A., Baurmeister U., Brunet P., et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003, 63:1934-1943.
5. Duranton F., Cohen G., De Smet R., Rodriguez M., Jankowski J., Vanholder R., et al. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol 2012, 23:1258-1270.
6. Itoh Y., Ezawa A., Kikuchi K., Tsuruta Y., Niwa T. 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, 403:1841-1850.
7. Sirich T.L., Aronov P.A., Plummer N.S., Hostetter T.H., Meyer T.W. Numerous protein-bound solutes are cleared by the kidney with high efficiency. Kidney Int 2013, 84:585-590.
8. Weisiger R.A. Dissociation from albumin: a potentially rate-limiting step in the clearance of substances by the liver. Proc Natl Acad Sci U S A. 1985, 82:1563-1567.
9. Noy N., Leonard M., Zakim D. The kinetics of interactions of bilirubin with lipid bilayers and with serum albumin. Biophys Chem 1992, 42:177-188.
10. Peters T. Ligand binding by albumin. All about albumin 1996, 79-132. Academic Press, San Diego.
11. Yoo M.J., Hage D.S. High-throughput analysis of drug dissociation from serum proteins using affinity silica monoliths. J Sep Sci 2011, 34:2255-2263.
12. Thornalley P.J., Rabbani N. Highlights and hotspots of protein glycation in end-stage renal disease. Semin Dial 2009, 22:400-404.
13. Niwa T., Maeda K., Ohki T., Saito A., Kobayashi K. A gas chromatographic-mass spectrometric analysis for phenols in uremic serum. Clin Chim Acta 1981, 110:51-57.
14. Jankowski J., Westhof T., Vaziri N.D., Ingrosso D., Perna A.F. Gasses as uremic toxins: is there something in the air?. Semin Nephrol 2014, 34:135-150.
15. Meijers B., Glorieux G., Poesen R., Bakker S. Non-extracorporeal methods for decreasing uremic solute concentration: a future way to go?. Semin Nephrol 2014, 34:228-243.
16. Niwa T., Ise M. Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med 1994, 124:96-104.
17. 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, 14:207-212.
18. Miyazaki T., Ise M., Seo H., Niwa T. Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys. Kidney Int Suppl 1997, 62:S15-22.
19. Miyazaki T., Ise M., Hirata M., Endo K., Ito Y., Seo H., et al. Indoxyl sulfate stimulates renal synthesis of transforming growth factor-beta 1 and progression of renal failure. Kidney Int Suppl 1997, 63:S211-S214.
20. Niwa T., Miyazaki T., Tsukushi S., Maeda K., Tsubakihara Y., Owada A., et al. Accumulation of indoxyl-beta-D-glucuronide in uremic serum: suppression of its production by oral sorbent and efficient removal by hemodialysis. Nephron 1996, 74:72-78.
21. Shimizu H., Saito S., Higashiyama Y., Nishijima F., Niwa T. CREB, NF-kappaB, and NADPH oxidase coordinately upregulate indoxyl sulfate-induced angiotensinogen expression in proximal tubular cells. Am J Physiol Cell Physiol 2013, 304:C685-C692.
22. Niwa T. Organic acids and the uremic syndrome: protein metabolite hypothesis in the progression of chronic renal failure. Semin Nephrol 1996, 16:167-182.
23. 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 Suppl 1997, 62:S23-S28.
24. Enomoto A., Takeda M., Tojo A., Sekine T., Cha S.H., Khamdang S., 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, 13:1711-1720.
25. Enomoto A., Takeda M., Taki K., Takayama F., Noshiro R., Niwa T., et al. Interactions of human organic anion as well as cation transporters with indoxyl sulfate. Eur J Pharmacol 2003, 466:13-20.
26. Taki K., Nakamura S., Miglinas M., Enomoto A., Niwa T. Accumulation of indoxyl sulfate in OAT1/3-positive tubular cells in kidneys of patients with chronic renal failure. J Ren Nutr 2006, 16:199-203.
27. Owada S., Goto S., Bannai K., Hayashi H., Nishijima F., Niwa T. Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats. Am J Nephrol 2008, 28:446-454.
28. Shimizu H., Bolati D., Higashiyama Y., Nishijima F., Shimizu K., Niwa T. Indoxyl sulfate upregulates renal expression of MCP-1 via production of ROS and activation of NF-kappaB, p53, ERK, and JNK in proximal tubular cells. Life Sci 2012, 90:525-530.
29. Shimizu H., Yisireyili M., Higashiyama Y., Nishijima F., Niwa T. Indoxyl sulfate upregulates renal expression of ICAM-1 via production of ROS and activation of NF-kappaB and p53 in proximal tubular cells. Life Sci 2013, 92:143-148.
30. Bolati D., Shimizu H., Higashiyama Y., Nishijima F., Niwa T. Indoxyl sulfate induces epithelial-to-mesenchymal transition in rat kidneys and human proximal tubular cells. Am J Nephrol 2011, 34:318-323.
31. Kim S.H., Yu M.A., Ryu E.S., Jang Y.H., Kang D.H. Indoxyl sulfate-induced epithelial-to-mesenchymal transition and apoptosis of renal tubular cells as novel mechanisms of progression of renal disease. Lab Invest 2012, 92:488-498.
32. Motojima M., Hosokawa A., Yamato H., Muraki T., Yoshioka T. Uremic toxins of organic anions up-regulate PAI-1 expression by induction of NF-kappaB and free radical in proximal tubular cells. Kidney Int 2003, 63:1671-1680.
33. Bolati D., Shimizu H., Yisireyili M., Nishijima F., Niwa T. Indoxyl sulfate, a uremic toxin, downregulates renal expression of Nrf2 through activation of NF-kappaB. BMC Nephrol 2013, 14:56.
34. Gelasco A.K., Raymond J.R. Indoxyl sulfate induces complex redox alterations in mesangial cells. Am J Physiol Renal Physiol 2006, 290:F1551-F1558.
35. Adijiang A., Shimizu H., Higuchi Y., Nishijima F., Niwa T. Indoxyl sulfate reduces klotho expression and promotes senescence in the kidneys of hypertensive rats. J Ren Nutr 2011, 21:105-109.
36. Shimizu H., Bolati D., Adijiang A., Adelibieke Y., Muteliefu G., Enomoto A., et al. Indoxyl sulfate downregulates renal expression of Klotho through production of ROS and activation of nuclear factor-kB. Am J Nephrol 2011, 33:319-324.
37. Sun C.Y., Chang S.C., Wu M.S. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int 2012, 81:640-650.
38. Shimizu H., Bolati D., Adijiang A., Enomoto A., Nishijima F., Dateki M., 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-C1117.
39. Shimizu H., Bolati D., Adijiang A., Muteliefu G., Enomoto A., Nishijima F., et al. NF-kappaB plays an important role in indoxyl sulfate-induced cellular senescence, fibrotic gene expression, and inhibition of proliferation in proximal tubular cells. Am J Physiol Cell Physiol 2011, 301:C1201-C1212.
40. Shimizu H., Yisireyili M., Nishijima F., Niwa T. Indoxyl sulfate enhances p53-TGF-beta1-Smad3 pathway in proximal tubular cells. Am J Nephrol 2013, 37:97-103.
41. Palm F., Nangaku M., Fasching A., Tanaka T., Nordquist L., Hansell P., 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-F386.
42. Kawakami T., Inagi R., Wada T., Tanaka T., Fujita T., Nangaku M. Indoxyl sulfate inhibits proliferation of human proximal tubular cells via endoplasmic reticulum stress. Am J Physiol Renal Physiol 2010, 299:F568-F576.
43. Tanaka T., Yamaguchi J., Higashijima Y., Nangaku M. 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, 27:4059-4075.
44. Chiang C.K., Tanaka T., Inagi R., Fujita T., Nangaku M. Indoxyl sulfate, a representative uremic toxin, suppresses erythropoietin production in a HIF-dependent manner. Lab Invest 2011, 91:1564-1571.
45. Watanabe H., Miyamoto Y., Honda D., Tanaka H., Wu Q., Endo M., et al. p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int 2013, 83:582-592.
46. Wu I.W., Hsu K.H., Lee C.C., Sun C.Y., Hsu H.J., Tsai C.J., et al. p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant 2011, 26:938-947.
47. Niwa T., Ise M. Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med 1994, 124:96-104.
48. Niwa T., Yazawa T., Ise M., Sugano M., Kodama T., Uehara Y., et al. Inhibitory effect of oral sorbent on accumulation of albumin-bound indoxyl sulfate in serum of experimental uremic rats. Nephron 1991, 57:84-88.
49. Niwa T., Emoto Y., Maeda K., Uehara Y., Yamada N., Shibata M. Oral sorbent suppresses accumulation of albumin-bound indoxyl sulphate in serum of haemodialysis patients. Nephrol Dial Transplant 1991, 6:105-109.
50. Niwa T., Tsukushi S., Ise M., Miyazaki T., Tsubakihara Y., Owada A., et al. Indoxyl sulfate and progression of renal failure: effects of a low-protein diet and oral sorbent on indoxyl sulfate production in uremic rats and undialyzed uremic patients. Miner Electrolyte Metab 1997, 23:179-184.
51. 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 2000, 15:1773-1781.
52. Schulman G., Agarwal R., Acharya M., Berl T., Blumenthal S., Kopyt N. A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD. Am J Kidney Dis 2006, 47:565-577.
53. Iida S., Kohno K., Yoshimura J., Ueda S., Usui M., Miyazaki H., et al. Carbonic-adsorbent AST-120 reduces overload of indoxyl sulfate and the plasma level of TGF-beta1 in patients with chronic renal failure. Clin Exp Nephrol 2006, 10:262-267.
54. Schulman G, Berl T, Beck G, Remuzzi G, Ritz E EPPIC: results from 2 phase III, randomized, placebo-controlled, double-blind trials of AST-120 in adults with CKD. Annual Meeting of the American Society of Nephrology; Philadelphia, PA. November 12, 2012.
55. Liabeuf S., Neirynck N., Drüeke T.B., Vanholder R., Massy Z.A. Clinical studies and uremia: what did we learn recently?. Semin Nephrol 2014, 34:164-179.
56. Schepers E., Meert N., Glorieux G., Goeman J., Van der Eycken J., Vanholder R. P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production. Nephrol Dial Transplant 2007, 22:592-596.
57. Meert N., Schepers E., Glorieux G., Van Landschoot M., Goeman J.L., Waterloos M.A., et al. Novel method for simultaneous determination of p-cresylsulphate and p-cresylglucuronide: clinical data and pathophysiological implications. Nephrol Dial Transplant 2012, 27:2388-2396.
58. Masai N., Tatebe J., Yoshino G., Morita T. Indoxyl sulfate stimulates monocyte chemoattractant protein-1 expression in human umbilical vein endothelial cells by inducing oxidative stress through activation of the NADPH oxidase-nuclear factor-kappaB pathway. Circ J. 2010, 74:2216-2224.
59. Tumur Z., Shimizu H., Enomoto A., Miyazaki H., Niwa T. Indoxyl sulfate upregulates expression of ICAM-1 and MCP-1 by oxidative stress-induced NF-kappaB activation. Am J Nephrol 2010, 31:435-441.
60. Pletinck A., Glorieux G., Schepers E., Cohen G., Gondouin B., Van Landschoot M., et al. Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall. J Am Soc Nephrol 2013, 24:1981-1994.
61. Dou L., Jourde-Chiche N., Faure V., Cerini C., Berland Y., Dignat-George F., et al. The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells. J Thromb Haemost 2007, 5:1302-1308.
62. Faure V., Dou L., Sabatier F., Cerini C., Sampol J., Berland Y., et al. Elevation of circulating endothelial microparticles in patients with chronic renal failure. J Thromb Haemost 2006, 4:566-573.
63. Meijers B.K., Van Kerckhoven S., Verbeke K., Dehaen W., Vanrenterghem Y., Hoylaerts M.F., et al. The uremic retention solute p-cresyl sulfate and markers of endothelial damage. Am J Kidney Dis 2009, 54:891-901.
64. Amabile N., Guerin A.P., Leroyer A., Mallat Z., Nguyen C., Boddaert J., et al. Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. J Am Soc Nephrol 2005, 16:3381-3388.
65. Wattanakit K., Cushman M., Stehman-Breen C., Heckbert S.R., Folsom A.R. Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol 2008, 19:135-140.
66. Folsom A.R., Lutsey P.L., Astor B.C., Wattanakit K., Heckbert S.R., Cushman M. Chronic kidney disease and venous thromboembolism: a prospective study. Nephrol Dial Transplant 2010, 25:3296-3301.
67. Gondouin B., Cerini C., Dou L., Sallee M., Duval-Sabatier A., Pletinck A., et al. Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway. Kidney Int 2013, 84:733-744.
68. Chitalia V.C., Shivanna S., Martorell J., Balcells M., Bosch I., Kolandaivelu K., et al. Uremic serum and solutes increase post-vascular interventional thrombotic risk through altered stability of smooth muscle cell tissue factor. Circulation 2013, 127:365-376.
69. Pawlak K., Mysliwiec M., Pawlak D. Hypercoagulability is independently associated with kynurenine pathway activation in dialysed uraemic patients. Thromb Haemost 2009, 102:49-55.
70. Dou L., Bertrand E., Cerini C., Faure V., Sampol J., Vanholder R., et al. The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair. Kidney Int 2004, 65:442-451.
71. Jourde-Chiche N., Dou L., Sabatier F., Calaf R., Cerini C., Robert S., et al. Levels of circulating endothelial progenitor cells are related to uremic toxins and vascular injury in hemodialysis patients. J Thromb Haemost 2009, 7:1576-1584.
72. Adijiang A., Goto S., Uramoto S., Nishijima F., Niwa T. Indoxyl sulphate promotes aortic calcification with expression of osteoblast-specific proteins in hypertensive rats. Nephrol Dial Transplant 2008, 23:1892-1901.
73. Adijiang A., Higuchi Y., Nishijima F., Shimizu H., Niwa T. Indoxyl sulfate, a uremic toxin, promotes cell senescence in aorta of hypertensive rats. Biochem Biophys Res Commun 2010, 399:637-641.
74. Muteliefu G., Enomoto A., Jiang P., Takahashi M., Niwa T. Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells. Nephrol Dial Transplant 2009, 24:2051-2058.
75. Yamamoto H., Tsuruoka S., Ioka T., Ando H., Ito C., Akimoto T., et al. Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells. Kidney Int. 2006, 69:1780-1785.
76. 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.
77. Lin C.Y., Hsu S.C., Lee H.S., Lin S.H., Tsai C.S., Huang S.M., et al. Enhanced expression of glucose transporter-1 in vascular smooth muscle cells via the Akt/tuberous sclerosis complex subunit 2 (TSC2)/mammalian target of rapamycin (mTOR)/ribosomal S6 protein kinase (S6K) pathway in experimental renal failure. J Vasc Surg 2013, 57:475-485.
78. Muteliefu G., Shimizu H., Enomoto A., Nishijima F., Takahashi M., Niwa T. 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-C134.
79. 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, 29:551-557.
80. Adelibieke Y., Shimizu H., Muteliefu G., Bolati D., Niwa T. Indoxyl sulfate induces endothelial cell senescence by increasing reactive oxygen species production and p53 activity. J Ren Nutr 2012, 22:86-89.
81. Ito S., Osaka M., Higuchi Y., Nishijima F., Ishii H., Yoshida M. Indoxyl sulfate induces leukocyte-endothelial interactions through up-regulation of E-selectin. J Biol Chem 2010, 285:38869-38875.
82. Kharait S., Haddad D.J., Springer M.L. Nitric oxide counters the inhibitory effects of uremic toxin indoxyl sulfate on endothelial cells by governing ERK MAP kinase and myosin light chain activation. Biochem Biophys Res Commun 2011, 409:758-763.
83. Peng Y.S., Lin Y.T., Chen Y., Hung K.Y., Wang S.M. Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism. J Cell Biochem 2012, 113:1034-1043.
84. Ryu J.H., Kim S.J. Clopidogrel effectively suppresses endothelial microparticle generation induced by indoxyl sulfate via inhibition of the p38 mitogen-activated protein kinase pathway. Blood Purif 2011, 32:186-194.
85. Wu V.C., Young G.H., Huang P.H., Lo S.C., Wang K.C., Sun C.Y., et al. In acute kidney injury, indoxyl sulfate impairs human endothelial progenitor cells: modulation by statin. Angiogenesis 2013, 16:609-624.
86. Adelibieke Y., Shimizu H., Saito S., Mironova R., Niwa T. Indoxyl sulfate counteracts endothelial effects of erythropoietin through suppression of Akt phosphorylation. Circ J. 2013, 77:1326-1336.
87. Lekawanvijit S., Adrahtas A., Kelly D.J., Kompa A.R., Wang B.H., Krum H. Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes?. Eur Heart J 2010, 31:1771-1779.
88. Yisireyili M., Shimizu H., Saito S., Enomoto A., Nishijima F., Niwa T. Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats. Life Sci 2013, 92:1180-1185.
89. Fujii H., Nishijima F., Goto S., Sugano M., Yamato H., Kitazawa R., 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, 24:2089-2095.
90. Taki K., Tsuruta Y., Niwa T. Indoxyl sulfate and atherosclerotic risk factors in hemodialysis patients. Am J Nephrol 2007, 27:30-35.
91. Barreto F.C., Barreto D.V., Liabeuf S., Meert N., Glorieux G., Temmar M., et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol 2009, 4:1551-1558.
92. Lin C.J., Liu H.L., Pan C.F., Chuang C.K., Jayakumar T., Wang T.J., et al. Indoxyl sulfate predicts cardiovascular disease and renal function deterioration in advanced chronic kidney disease. Arch Med Res 2012, 43:451-456.
93. Melamed M.L., Plantinga L., Shafi T., Parekh R., Meyer T.W., Hostetter T.H., et al. Retained organic solutes, patient characteristics and all-cause and cardiovascular mortality in hemodialysis: results from the retained organic solutes and clinical outcomes (ROSCO) investigators. BMC Nephrol 2013, 14:134.
94. Sato B., Yoshikawa D., Ishii H., Kikuchi R., Arima T., Takeshita K., et al. Indoxyl sulfate, a uremic toxin, and carotid intima-media thickness in patients with coronary artery disease. Int J Cardiol 2013, 163:214-216.
95. Shimazu S., Hirashiki A., Okumura T., Yamada T., Okamoto R., Shinoda N., et al. Association between indoxyl sulfate and cardiac dysfunction and prognosis in patients with dilated cardiomyopathy. Circ J. 2013, 77:390-396.
96. Sato B., Yoshikawa D., Ishii H., Suzuki S., Inoue Y., Takeshita K., et al. Relation of plasma indoxyl sulfate levels and estimated glomerular filtration rate to left ventricular diastolic dysfunction. Am J Cardiol 2013, 111:712-716.
97. Hsu C.C., Lu Y.C., Chiu C.A., Yu T.H., Hung W.C., Wang C.P., et al. Levels of indoxyl sulfate are associated with severity of coronary atherosclerosis. Clin Invest Med 2013, 36:E42-E49.
98. Chiu C.A., Lu L.F., Yu T.H., Hung W.C., Chung F.M., Tsai I.T., et al. Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated with coronary artery disease in patients with diabetic nephropathy. Rev Diabet Stud 2010, 7:275-284.
99. Lin C.J., Pan C.F., Liu H.L., Chuang C.K., Jayakumar T., Wang T.J., et al. The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis. Atherosclerosis 2012, 225:173-179.
100. Wang C.P., Lu L.F., Yu T.H., Hung W.C., Chiu C.A., Chung F.M., et al. Serum levels of total p-cresylsulphate are associated with angiographic coronary atherosclerosis severity in stable angina patients with early stage of renal failure. Atherosclerosis 2010, 211:579-583.
101. Wang C.P., Lu L.F., Yu T.H., Hung W.C., Chiu C.A., Chung F.M., et al. Associations among chronic kidney disease, high total p-cresylsulfate and major adverse cardiac events. J Nephrol 2013, 26:111-118.
102. Liabeuf S., Barreto D.V., Barreto F.C., Meert N., Glorieux G., Schepers E., et al. Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease. Nephrol Dial Transplant 2010, 25:1183-1191.
103. Wu I.W., Hsu K.H., Hsu H.J., Lee C.C., Sun C.Y., Tsai C.J., et al. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients--a prospective cohort study. Nephrol Dial Transplant 2012, 27:1169-1175.
104. Nakamura T., Kawagoe Y., Matsuda T., Ueda Y., Shimada N., Ebihara I., et al. Oral ADSORBENT AST-120 decreases carotid intima-media thickness and arterial stiffness in patients with chronic renal failure. Kidney Blood Press Res 2004, 27:121-126.
105. Ueda H., Shibahara N., Takagi S., Inoue T., Katsuoka Y. AST-120 treatment in pre-dialysis period affects the prognosis in patients on hemodialysis. Ren Fail 2008, 30:856-860.
106. Shibahara H., Shibahara N. Cardiorenal protective effect of the oral uremic toxin absorbent AST-120 in chronic heart disease patients with moderate CKD. J Nephrol 2010, 23:535-540.
107. Yu M., Kim Y.J., Kang D.H. Indoxyl sulfate-induced endothelial dysfunction in patients with chronic kidney disease via an induction of oxidative stress. Clin J Am Soc Nephrol 2011, 6:30-39.
108. Nakai K., Fujii H., Kono K., Goto S., Fukagawa M., Nishi S. Effects of AST-120 on left ventricular mass in predialysis patients. Am J Nephrol 2011, 33:218-223.
109. Nii-Kono T., Iwasaki Y., Uchida M., Fujieda A., Hosokawa A., Motojima M., et al. Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells. Kidney Int 2007, 71:738-743.
110. Mozar A., Louvet L., Godin C., Mentaverri R., Brazier M., Kamel S., et al. Indoxyl sulphate inhibits osteoclast differentiation and function. Nephrol Dial Transplant 2012, 27:2176-2181.
111. Schreiner G., Maher J. Biochemistry of uremia. Uremia 1960, 55-85. Charles Thomas, Springfield.
112. Deguchi T., Isozaki K., Yousuke K., Terasaki T., Otagiri M. Involvement of organic anion transporters in the efflux of uremic toxins across the blood-brain barrier. J Neurochem 2006, 96:1051-1059.
113. Hosoya K.I., Tachikawa M. Roles of organic anion/cation transporters at the blood-brain and blood-cerebrospinal fluid barriers involving uremic toxins. Clin Exp Nephrol 2011, 15:478-485.
114. Mullen W., Saigusa D., Abe T., Adamski J., Mischak H. The kidney and uremic toxin removal: glomerulus or tubulus?. Semin Nephrol 2014, 34:180-190.
115. Porter R.D., Cathcart-Rake W.F., Wan S.H., Whittier F.C., Grantham J.J. Secretory activity and aryl acid content of serum, urine, and cerebrospinal fluid in normal and uremic man. J Lab Clin Med 1975, 85:723-731.
116. Spector R., Snodgrass S.R. The effect of uremia on penicillin flux between blood and cerebrospinal fluid. J Lab Clin Med 1976, 87:749-759.
117. Muting D. Studies on the pathogenesis of uremia. Comparative determinations of glucuronic acid, indican, free and bound phenols in the serum, cerebrospinal fluid, and urine of renal diseases with and without uremia. Clin Chim Acta 1965, 12:551-554.
118. D'Hooge R., Van de Vijver G., Van Bogaert P.P., Marescau B., Vanholder R., De Deyn P.P. Involvement of voltage- and ligand-gated Ca2+ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins. Kidney Int 2003, 63:1764-1775.
119. Dasgupta A. Usefulness of monitoring free (unbound) concentrations of therapeutic drugs in patient management. Clin Chim Acta 2007, 377:1-13.
120. Piafsky K.M. Disease-induced changes in the plasma binding of basic drugs. Clin Pharmacokinet 1980, 5:246-262.
121. Vanholder R., Van Landschoot N., De Smet R., Schoots A., Ringoir S. Drug protein binding in chronic renal failure: evaluation of nine drugs. Kidney Int 1988, 33:996-1004.
122. Peters T. Clinical aspects: albumin in medicine. All about albumin 1996, 251-284. Academic Press, San Diego.
123. Oettl K., Stauber R.E. Physiological and pathological changes in the redox state of human serum albumin critically influence its binding properties. Br J Pharmacol 2007, 151:580-590.
124. Sun H., Frassetto L., Benet L.Z. Effects of renal failure on drug transport and metabolism. Pharmacol Ther 2006, 109:1-11.
125. Eloot S., Ledebo I., Ward R.A. Extracorporeal removal of uremic toxins: can we still do better?. Semin Nephrol 2014, 34:209-227.