Skip to main content
SpringerLink
Log in

Uremic Toxin-Related Systemic Disorders

  • Chapter
  • First Online:
Uremic Toxins and Organ Failure

  • 250 Accesses

Abstract

Patients with chronic kidney disease (CKD), particularly those undergoing dialysis, have worse clinical outcomes owing to the development of various systemic disorders, such as cardiovascular disease, mineral and bone disorders, and infectious disease. The direct or indirect interaction between various uremic toxins and organ/tissues induce systemic disorders in patients with CKD, known as “uremic toxin-related systemic disorders.” Among various uremic toxins, protein-bound uremic toxins (PBUTs) produced from dietary protein show the strong toxicity for various systemic disorders, and are difficult to remove using conventional hemodialysis owing to their high protein binding property. The interventional strategies for the uremic toxins are (1) management of protein intake, (2) inhibition of production of the precursors by intestinal bacteria, (3) inhibition of the reaction between uremic toxins and organs/tissues, and (4) removal of the uremic toxins with medication or blood purification treatment. Recent progress of dialysis treatment has improved small- and middle-size molecules, but it is still insufficient for PBUTs. Although an effective therapeutic approach to decrease these solutes is not available, adsorption methods may be one of the attractive strategies to remove them.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Lekawanvijit S, Kompa AR, Wang BH, Kelly DJ, Krum H. Cardiorenal syndrome: the emerging role of protein-bound uremic toxins. Circ Res. 2012;111(11):1470–83.

    Article  CAS  PubMed  Google Scholar 

  2. Barreto FC, Barreto DV, Liabeuf S, Meert N, Glorieux G, Temmar M, Choukroun G, Vanholder R, Massy ZA. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009;4(10):1551–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y. Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney Int. 2006;69(6):1081–7.

    Article  CAS  PubMed  Google Scholar 

  4. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A, European Uremic Toxin Work G. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012;23(7):1258–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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(7):1841–50.

    Article  CAS  PubMed  Google Scholar 

  6. Niwa T, Ise M. Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J Lab Clin Med. 1994;124(1):96–104.

    CAS  PubMed  Google Scholar 

  7. Shimizu H, Bolati D, Adijiang A, Enomoto A, Nishijima F, Dateki M, Niwa T. Senescence and dysfunction of proximal tubular cells are associated with activated p53 expression by indoxyl sulfate. Am J Cell Physiol. 2010;299(5):C1110–7.

    Article  CAS  Google Scholar 

  8. Kikuchi K, Saigusa D, Kanemitsu Y, Matsumoto Y, Thanai P, Suzuki N, Mise K, Yamaguchi H, Nakamura T, Asaji K, Mukawa C, Tsukamoto H, Sato T, Oikawa Y, Iwasaki T, Oe Y, Tsukimi T, Fukuda NN, Ho HJ, Nanto-Hara F, Ogura J, Saito R, Nagao S, Ohsaki Y, Shimada S, Suzuki T, Toyohara T, Mishima E, Shima H, Akiyama Y, Akiyama Y, Ichijo M, Matsuhashi T, Matsuo A, Ogata Y, Yang CC, Suzuki C, Breeggemann MC, Heymann J, Shimizu M, Ogawa S, Takahashi N, Suzuki T, Owada Y, Kure S, Mano N, Soga T, Wada T, Kopp JB, Fukuda S, Hozawa A, Yamamoto M, Ito S, Wada J, Tomioka Y, Abe T. Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. Nat Commun. 2019;10(1):1835.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Wakasugi M, Kazama JJ, Yamamoto S, Kawamura K, Narita I. Cause-specific excess mortality among dialysis patients: comparison with the general population in Japan. Ther Apher Dial. 2013;17(3):298–304.

    Article  PubMed  Google Scholar 

  10. Yamamoto S, Kon V. Mechanisms for increased cardiovascular disease in chronic kidney dysfunction. Curr Opin Nephrol Hypertens. 2009;18(3):181–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, Wanner C, Krane V, Cass A, Craig J, Neal B, Jiang L, Hooi LS, Levin A, Agodoa L, Gaziano M, Kasiske B, Walker R, Massy ZA, Feldt-Rasmussen B, Krairittichai U, Ophascharoensuk V, Fellstrom B, Holdaas H, Tesar V, Wiecek A, Grobbee D, de Zeeuw D, Gronhagen-Riska C, Dasgupta T, Lewis D, Herrington W, Mafham M, Majoni W, Wallendszus K, Grimm R, Pedersen T, Tobert J, Armitage J, Baxter A, Bray C, Chen Y, Chen Z, Hill M, Knott C, Parish S, Simpson D, Sleight P, Young A, Collins R, Investigators S. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, Ritz E, German D, Dialysis Study I. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238–48.

    Article  CAS  PubMed  Google Scholar 

  13. Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Gronhagen-Riska C, De Lima JJ, Lins R, Mayer G, McMahon AW, Parving HH, Remuzzi G, Samuelsson O, Sonkodi S, Sci D, Suleymanlar G, Tsakiris D, Tesar V, Todorov V, Wiecek A, Wuthrich RP, Gottlow M, Johnsson E, Zannad F, Group, A. S. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395–407.

    Article  CAS  PubMed  Google Scholar 

  14. Gregg LP, Hedayati SS. Management of traditional cardiovascular risk factors in CKD: what are the data? Am J Kidney Dis. 2018;72:728.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW, American Heart Association Councils on Kidney in Cardiovascular Disease, H. B. P. R. C. C.; Epidemiology; Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension. 2003;42(5):1050–65.

    Article  CAS  PubMed  Google Scholar 

  16. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351(13):1296–305.

    Article  CAS  PubMed  Google Scholar 

  17. Tonelli M, Muntner P, Lloyd A, Manns BJ, Klarenbach S, Pannu N, James MT, Hemmelgarn BR, Alberta Kidney Disease N. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet. 2012;380(9844):807–14.

    Article  PubMed  Google Scholar 

  18. Bain MA, Faull R, Fornasini G, Milne RW, Evans AM. Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrol Dial Transpl. 2006;21(5):1300–4.

    Article  CAS  Google Scholar 

  19. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Liabeuf S, Lenglet A, Desjardins L, Neirynck N, Glorieux G, Lemke HD, Vanholder R, Diouf M, Choukroun G, Massy ZA, European Uremic Toxin Work G. Plasma beta-2 microglobulin is associated with cardiovascular disease in uremic patients. Kidney Int. 2012;82(12):1297–303.

    Article  CAS  PubMed  Google Scholar 

  21. Barreto FC, Barreto DV, Liabeuf S, Meert N, Glorieux G, Temmar M, Choukroun G, Vanholder R, Massy ZA, European Uremic Toxin Work G. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009;4(10):1551–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dou L, Sallee M, Cerini C, Poitevin S, Gondouin B, Jourde-Chiche N, Fallague K, Brunet P, Calaf R, Dussol B, Mallet B, Dignat-George F, Burtey S. The cardiovascular effect of the uremic solute indole-3 acetic acid. J Am Soc Nephrol. 2015;26(4):876–87.

    Article  CAS  PubMed  Google Scholar 

  23. Shafi T, Sirich TL, Meyer TW, Hostetter TH, Plummer NS, Hwang S, Melamed ML, Banerjee T, Coresh J, Powe NR. Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are not associated with cardiovascular outcomes. Kidney Int. 2017;92(6):1484–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yamamoto S, Zuo Y, Ma J, Yancey PG, Hunley TE, Motojima M, Fogo AB, Linton MF, Fazio S, Ichikawa I, Kon V. Oral activated charcoal adsorbent (AST-120) ameliorates extent and instability of atherosclerosis accelerated by kidney disease in apolipoprotein E-deficient mice. Nephrol Dial Transpl. 2011;26(8):2491–7.

    Article  CAS  Google Scholar 

  26. Suganuma E, Zuo Y, Ayabe N, Ma J, Babaev VR, Linton MF, Fazio S, Ichikawa I, Fogo AB, Kon V. Antiatherogenic effects of angiotensin receptor antagonism in mild renal dysfunction. J Am Soc Nephrol. 2006;17(2):433–41.

    Article  CAS  PubMed  Google Scholar 

  27. Bro S, Bentzon JF, Falk E, Andersen CB, Olgaard K, Nielsen LB. Chronic renal failure accelerates atherogenesis in apolipoprotein E-deficient mice. J Am Soc Nephrol. 2003;14(10):2466–74.

    Article  CAS  PubMed  Google Scholar 

  28. Fujii H, Nishijima F, Goto S, Sugano M, Yamato H, Kitazawa R, Kitazawa S, Fukagawa M. Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress. Nephrol Dial Transpl. 2009;24(7):2089–95.

    Article  CAS  Google Scholar 

  29. Yamamoto S, Yancey PG, Zuo Y, Ma LJ, Kaseda R, Fogo AB, Ichikawa I, Linton MF, Fazio S, Kon V. Macrophage polarization by angiotensin II-type 1 receptor aggravates renal injury-acceleration of atherosclerosis. Arterioscler Thromb Vasc Biol. 2011;31(12):2856–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nakano T, Katsuki S, Chen M, Decano JL, Halu A, Lee LH, Pestana DVS, Kum AST, Kuromoto RK, Golden WS, Boff MS, Guimaraes GC, Higashi H, Kauffman KJ, Maejima T, Suzuki T, Iwata H, Barabasi AL, Aster JC, Anderson DG, Sharma A, Singh SA, Aikawa E, Aikawa M. Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation via the interplay of OATP2B1 and Dll4-notch signaling. Circulation. 2019;139(1):78–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wakamatsu T, Yamamoto S, Ito T, Sato Y, Matsuo K, Takahashi Y, Kaneko Y, Goto S, Kazama JJ, Gejyo F, Narita I. Indoxyl sulfate promotes macrophage IL-1beta production by activating aryl hydrocarbon receptor/NF-kappa/MAPK cascades, but the NLRP3 inflammasome was not activated. Toxins (Basel). 2018;10(3):124.

    Article  CAS  Google Scholar 

  32. Matsuo K, Yamamoto S, Wakamatsu T, Takahashi Y, Kawamura K, Kaneko Y, Goto S, Kazama JJ, Narita I. Increased proinflammatory cytokine production and decreased cholesterol efflux due to downregulation of ABCG1 in macrophages exposed to indoxyl sulfate. Toxins (Basel). 2015;7(8):3155–66.

    Article  CAS  Google Scholar 

  33. Masakane I, Nakai S, Ogata S, Kimata N, Hanafusa N, Hamano T, Wakai K, Wada A, Nitta K. An overview of regular dialysis treatment in Japan (as of 31 December 2013). Ther Apher Dial. 2015;19(6):540–74.

    Article  CAS  PubMed  Google Scholar 

  34. Cheung AK, Greene T, Leypoldt JK, Yan G, Allon M, Delmez J, Levey AS, Levin NW, Rocco MV, Schulman G, Eknoyan G, Group, H. S. Association between serum 2-microglobulin level and infectious mortality in hemodialysis patients. Clin J Am Soc Nephrol. 2008;3(1):69–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wu IW, Hsu KH, Hsu HJ, Lee CC, Sun CY, Tsai CJ, Wu MS. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients—a prospective cohort study. Nephrol Dial Transpl. 2012;27(3):1169–75.

    Article  CAS  Google Scholar 

  36. Adesso S, Popolo A, Bianco G, Sorrentino R, Pinto A, Autore G, Marzocco S. The uremic toxin indoxyl sulphate enhances macrophage response to LPS. PLoS One. 2013;8(9):e76778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wakasugi M, Kazama JJ, Taniguchi M, Wada A, Iseki K, Tsubakihara Y, Narita I. Increased risk of hip fracture among Japanese hemodialysis patients. J Bone Miner Metab. 2013;31(3):315–21.

    Article  PubMed  Google Scholar 

  38. Tentori F, McCullough K, Kilpatrick RD, Bradbury BD, Robinson BM, Kerr PG, Pisoni RL. High rates of death and hospitalization follow bone fracture among hemodialysis patients. Kidney Int. 2014;85(1):166–73.

    Article  PubMed  Google Scholar 

  39. Goto NA, Weststrate ACG, Oosterlaan FM, Verhaar MC, Willems HC, Emmelot-Vonk MH, Hamaker ME. The association between chronic kidney disease, falls, and fractures: a systematic review and meta-analysis. Osteoporos Int. 2020;31(1):13–29.

    Article  CAS  PubMed  Google Scholar 

  40. Yamamoto S, Fukagawa M. Uremic toxicity and bone in CKD. J Nephrol. 2017;30(5):623–7.

    Article  PubMed  Google Scholar 

  41. Sprague SM, Bellorin-Font E, Jorgetti V, Carvalho AB, Malluche HH, Ferreira A, D’Haese PC, Drueke TB, Du H, Manley T, Rojas E, Moe SM. Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. Am J Kidney Dis. 2016;67(4):559–66.

    Article  PubMed  Google Scholar 

  42. Iwasaki Y, Kazama JJ, Yamato H, Fukagawa M. Changes in chemical composition of cortical bone associated with bone fragility in rat model with chronic kidney disease. Bone. 2011;48(6):1260–7.

    Article  CAS  PubMed  Google Scholar 

  43. Iwasaki Y, Kazama JJ, Yamato H, Shimoda H, Fukagawa M. Accumulated uremic toxins attenuate bone mechanical properties in rats with chronic kidney disease. Bone. 2013;57(2):477–83.

    Article  CAS  PubMed  Google Scholar 

  44. Tanaka H, Iwasaki Y, Yamato H, Mori Y, Komaba H, Watanabe H, Maruyama T, Fukagawa M. p-Cresyl sulfate induces osteoblast dysfunction through activating JNK and p38 MAPK pathways. Bone. 2013;56(2):347–54.

    Article  CAS  PubMed  Google Scholar 

  45. Gejyo F, Homma N, Suzuki Y, Arakawa M. Serum levels of beta 2-microglobulin as a new form of amyloid protein in patients undergoing long-term hemodialysis. N Engl J Med. 1986;314(9):585–6.

    Article  CAS  PubMed  Google Scholar 

  46. Hoshino J, Yamagata K, Nishi S, Nakai S, Masakane I, Iseki K, Tsubakihara Y. Significance of the decreased risk of dialysis-related amyloidosis now proven by results from Japanese nationwide surveys in 1998 and 2010. Nephrol Dial Transpl. 2016;31(4):595–602.

    Article  Google Scholar 

  47. Yamaguchi I, Hasegawa K, Naiki H, Mitsu T, Matuo Y, Gejyo F. Extension of a beta2M amyloid fibrils with recombinant human beta2-microglobulin. Amyloid. 2001;8(1):30–40.

    Article  CAS  PubMed  Google Scholar 

  48. Yamaguchi I, Suda H, Tsuzuike N, Seto K, Seki M, Yamaguchi Y, Hasegawa K, Takahashi N, Yamamoto S, Gejyo F, Naiki H. Glycosaminoglycan and proteoglycan inhibit the depolymerization of beta2-microglobulin amyloid fibrils in vitro. Kidney Int. 2003;64(3):1080–8.

    Article  CAS  PubMed  Google Scholar 

  49. Yamamoto S, Yamaguchi I, Hasegawa K, Tsutsumi S, Goto Y, Gejyo F, Naiki H. Glycosaminoglycans enhance the trifluoroethanol-induced extension of beta 2-microglobulin-related amyloid fibrils at a neutral pH. J Am Soc Nephrol. 2004;15(1):126–33.

    Article  CAS  PubMed  Google Scholar 

  50. Ookoshi T, Hasegawa K, Ohhashi Y, Kimura H, Takahashi N, Yoshida H, Miyazaki R, Goto Y, Naiki H. Lysophospholipids induce the nucleation and extension of beta2-microglobulin-related amyloid fibrils at a neutral pH. Nephrol Dial Transpl. 2008;23(10):3247–55.

    Article  CAS  Google Scholar 

  51. Noji M, Sasahara K, Yamaguchi K, So M, Sakurai K, Kardos J, Naiki H, Goto Y. Heating during agitation of beta2-microglobulin reveals that supersaturation breakdown is required for amyloid fibril formation at neutral pH. J Biol Chem. 2019;294(43):15826–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Mettang T, Kremer AE. Uremic pruritus. Kidney Int. 2015;87(4):685–91.

    Article  CAS  PubMed  Google Scholar 

  53. Wang CP, Lu YC, Tsai IT, Tang WH, Hsu CC, Hung WC, Yu TH, Chen SC, Chung FM, Lee YJ, Houng JY. Increased levels of Total p-cresylsulfate are associated with pruritus in patients with chronic kidney disease. Dermatology. 2016;232(3):363–70.

    Article  CAS  PubMed  Google Scholar 

  54. Narita I, Alchi B, Omori K, Sato F, Ajiro J, Saga D, Kondo D, Skatsume M, Maruyama S, Kazama JJ, Akazawa K, Gejyo F. Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients. Kidney Int. 2006;69(9):1626–32.

    Article  CAS  PubMed  Google Scholar 

  55. Lin YT, Wu PH, Liang SS, Mubanga M, Yang YH, Hsu YL, Kuo MC, Hwang SJ, Kuo PL. Protein-bound uremic toxins are associated with cognitive function among patients undergoing maintenance hemodialysis. Sci Rep. 2019;9(1):20388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Mishima E, Fukuda S, Mukawa C, Yuri A, Kanemitsu Y, Matsumoto Y, Akiyama Y, Fukuda NN, Tsukamoto H, Asaji K, Shima H, Kikuchi K, Suzuki C, Suzuki T, Tomioka Y, Soga T, Ito S, Abe T. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach. Kidney Int. 2017;92(3):634–45.

    Article  CAS  PubMed  Google Scholar 

  57. Mishima E, Fukuda S, Shima H, Hirayama A, Akiyama Y, Takeuchi Y, Fukuda NN, Suzuki T, Suzuki C, Yuri A, Kikuchi K, Tomioka Y, Ito S, Soga T, Abe T. Alteration of the intestinal environment by lubiprostone is associated with amelioration of adenine-induced CKD. J Am Soc Nephrol. 2015;26(8):1787–94.

    Article  CAS  PubMed  Google Scholar 

  58. McFarlane C, Ramos CI, Johnson DW, Campbell KL. Prebiotic, probiotic, and synbiotic supplementation in chronic kidney disease: a systematic review and meta-analysis. J Ren Nutr. 2019;29(3):209–20.

    Article  CAS  PubMed  Google Scholar 

  59. Schulman G, Berl T, Beck GJ, Remuzzi G, Ritz E, Arita K, Kato A, Shimizu M. Randomized placebo-controlled EPPIC trials of AST-120 in CKD. J Am Soc Nephrol. 2015;26(7):1732–46.

    Article  CAS  PubMed  Google Scholar 

  60. Akizawa T, Asano Y, Morita S, Wakita T, Onishi Y, Fukuhara S, Gejyo F, Matsuo S, Yorioka N, Kurokawa K, Group, C.-K. S. Effect of a carbonaceous oral adsorbent on the progression of CKD: a multicenter, randomized, controlled trial. Am J Kidney Dis. 2009;54(3):459–67.

    Article  CAS  PubMed  Google Scholar 

  61. Cha RH, Kang SW, Park CW, Cha DR, Na KY, Kim SG, Yoon SA, Han SY, Chang JH, Park SK, Lim CS, Kim YS. A randomized, controlled trial of Oral intestinal sorbent AST-120 on renal function deterioration in patients with advanced renal dysfunction. Clin J Am Soc Nephrol. 2016;11(4):559–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Cha RH, Kang SW, Park CW, Cha DR, Na KY, Kim SG, Yoon SA, Kim S, Han SY, Park JH, Chang JH, Lim CS, Kim YS. Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: post-hoc analysis of the Kremezin study against renal disease progression in Korea. Kidney Res Clin Pract. 2017;36(1):68–78.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Palmer SC, Rabindranath KS, Craig JC, Roderick PJ, Locatelli F, Strippoli GF. High-flux versus low-flux membranes for end-stage kidney disease. Cochrane Database Syst Rev. 2012;9:CD005016.

    Google Scholar 

  64. Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto R. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002;347(25):2010–9.

    Article  PubMed  Google Scholar 

  65. Basile C, Libutti P, Di Turo AL, Casino FG, Vernaglione L, Tundo S, Maselli P, De Nicolo EV, Ceci E, Teutonico A, Lomonte C. Removal of uraemic retention solutes in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis. Nephrol Dial Transpl. 2011;26(4):1296–303.

    Article  CAS  Google Scholar 

  66. Cornelis T, Eloot S, Vanholder R, Glorieux G, van der Sande FM, Scheijen JL, Leunissen KM, Kooman JP, Schalkwijk CG. Protein-bound uraemic toxins, dicarbonyl stress and advanced glycation end products in conventional and extended haemodialysis and haemodiafiltration. Nephrol Dial Transpl. 2015;30(8):1395–402.

    Article  CAS  Google Scholar 

  67. De Smet R, Dhondt A, Eloot S, Galli F, Waterloos MA, Vanholder R. Effect of the super-flux cellulose triacetate dialyser membrane on the removal of non-protein-bound and protein-bound uraemic solutes. Nephrol Dial Transpl. 2007;22(7):2006–12.

    Article  CAS  Google Scholar 

  68. Krieter DH, Hackl A, Rodriguez A, Chenine L, Moragues HL, Lemke HD, Wanner C, Canaud B. Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrol Dial Transpl. 2010;25(1):212–8.

    Article  CAS  Google Scholar 

  69. Meert N, Eloot S, Waterloos MA, Van Landschoot M, Dhondt A, Glorieux G, Ledebo I, Vanholder R. Effective removal of protein-bound uraemic solutes by different convective strategies: a prospective trial. Nephrol Dial Transpl. 2009;24(2):562–70.

    Article  CAS  Google Scholar 

  70. Gejyo F, Homma N, Hasegawa S, Arakawa M. A new therapeutic approach to dialysis amyloidosis: intensive removal of beta 2-microglobulin with adsorbent column. Artif Organs. 1993;17(4):240–3.

    Article  CAS  PubMed  Google Scholar 

  71. Gejyo F, Kawaguchi Y, Hara S, Nakazawa R, Azuma N, Ogawa H, Koda Y, Suzuki M, Kaneda H, Kishimoto H, Oda M, Ei K, Miyazaki R, Maruyama H, Arakawa M, Hara M. Arresting dialysis-related amyloidosis: a prospective multicenter controlled trial of direct hemoperfusion with a beta2-microglobulin adsorption column. Artif Organs. 2004;28(4):371–80.

    Article  CAS  PubMed  Google Scholar 

  72. Homma N, Gejyo F, Hasegawa S, Teramura T, Ei I, Maruyama H, Arakawa M. Effects of a new adsorbent column for removing beta-2-microglobulin from circulating blood of dialysis patients. Contrib Nephrol. 1995;112:164–71.

    Article  CAS  PubMed  Google Scholar 

  73. Kutsuki H. beta(2)-Microglobulin-selective direct hemoperfusion column for the treatment of dialysis-related amyloidosis. Biochim Biophys Acta. 2005;1753(1):141–5.

    Article  CAS  PubMed  Google Scholar 

  74. Yamamoto S, Sato M, Sato Y, Wakamatsu T, Takahashi Y, Iguchi A, Omori K, Suzuki Y, Ei I, Kaneko Y, Goto S, Kazama JJ, Gejyo F, Narita I. Adsorption of protein-bound uremic toxins through direct hemoperfusion with hexadecyl-immobilized cellulose beads in patients undergoing hemodialysis. Artif Organs. 2018;42(1):88–93.

    Article  CAS  PubMed  Google Scholar 

  75. Yamamoto S, Kazama JJ, Omori K, Matsuo K, Takahashi Y, Kawamura K, Matsuto T, Watanabe H, Maruyama T, Narita I. Continuous reduction of protein-bound uraemic toxins with improved oxidative stress by using the oral charcoal adsorbent AST-120 in haemodialysis patients. Sci Rep. 2015;5:14381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Tijink MS, Wester M, Glorieux G, Gerritsen KG, Sun J, Swart PC, Borneman Z, Wessling M, Vanholder R, Joles JA, Stamatialis D. Mixed matrix hollow fiber membranes for removal of protein-bound toxins from human plasma. Biomaterials. 2013;34(32):7819–28.

    Article  CAS  PubMed  Google Scholar 

  77. Meyer TW, Peattie JW, Miller JD, Dinh DC, Recht NS, Walther JL, Hostetter TH. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. J Am Soc Nephrol. 2007;18(3):868–74.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Blood Purification Therapy, Niigata University Medical and Dental Hospital, Niigata, Japan

    Suguru Yamamoto

  2. Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Suguru Yamamoto

Authors
  1. Suguru Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suguru Yamamoto .

Editor information

Editors and Affiliations

  1. Department of Pharmacy, Kumamoto University Hospital, Kumamoto University, Kumamoto, Japan

    Hideyuki Saito

  2. Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Takaaki Abe

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yamamoto, S. (2020). Uremic Toxin-Related Systemic Disorders. In: Saito, H., Abe, T. (eds) Uremic Toxins and Organ Failure. Springer, Singapore. https://doi.org/10.1007/978-981-15-7793-2_4

Download citation

  • DOI: https://doi.org/10.1007/978-981-15-7793-2_4

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-15-7792-5

  • Online ISBN: 978-981-15-7793-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation