Enhancing dialyser clearance—from target to development


Products of metabolism accumulate in kidney failure and potentially have toxic effects. Traditionally these uraemic toxins are classified as small, middle-sized and protein-bound toxins, and clearance during dialysis is affected by diffusion, convection and adsorption. As current dialysis practice effectively clears small solutes, increasing evidence supports a toxic effect for middle-sized and protein-bound toxins. Therefore, newer approaches to standard dialysis practice are required to look beyond urea clearance. Current dialysers have been developed to effectively clear small solutes and secondly to increase middle-sized toxin clearances. However, there is no ideal dialyser which can effectively clear all uraemic toxins. Advances in nanotechnology have led to improvements in manufacturing, with the production of smoother membrane surfaces and uniformity of pore size. The introduction of haemodiafiltration has led to changes in dialyser design to improve convective clearances. Both diffusional and convectional clearances can be increased by changing dialyser designs to alter blood and dialysate flows, and novel dialyser designs using microfluidics offer more efficient solute clearances. Adjusting surface hydrophilicity and charge alter adsorptive properties, and greater clearance of protein-bound toxins can be achieved by adding carbon or other absorptive monoliths into the circuit or by developing composite dialyser membranes. Other strategies to increase protein-bound toxins clearances have centred on disrupting binding and so displacing toxins from proteins. Just as the hollow fibre design replaced the flat plate dialyser, we are now entering a new era of dialyser designs aimed to increase the spectrum of uraemic toxins which can be cleared by dialysis.

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  1. 1.

    Twardowski ZJ (2008) History of hemodialyzers’ designs. Hemodial Int 12:173–210

    Article  PubMed  Google Scholar 

  2. 2.

    Ronco C, Brendolan A, Everard P, Irone M, Ballestri M, Cappelli G, Inguaggiato P, Bellomo R (1999) Cellulose triacetate: another membrane for continuous renal replacement therapy. J Nephrol 12:241–247

    CAS  PubMed  Google Scholar 

  3. 3.

    Ronco C, Brendolan A, Crepaldi C, Rodighiero M, Scabardi M (2002) Blood and dialysate flow distributions in hollow-fiber hemodialyzers analyzed by computerized helical scanning technique. J Am Soc Nephrol 13[Suppl 1]:S53–S61

    CAS  PubMed  Google Scholar 

  4. 4.

    Shibata E, Nagai K, Takeuchi R, Noda Y, Makino T, Chikata Y, Hann M, Yoshimoto S, Ono H, Ueda S, Tamaki M, Murakami T, Matsuura M, Abe H, Doi T (2015) Re-evaluation of pre-pump arterial pressure to avoid inadequate dialysis and hemolysis: importance of prepump arterial pressure monitoring in hemodialysis patients. Artif Organs 39:627–634

    Article  PubMed  Google Scholar 

  5. 5.

    Asano M, Thumma J, Oguchi K, Pisoni RL, Akizawa T, Akiba T, Fukuhara S, Kurokawa K, Ethier J, Saran R, Saito A, Group JDR (2013) Vascular access care and treatment practices associated with outcomes of arteriovenous fistula: international comparisons from the Dialysis Outcomes and Practice Patterns Study. Nephron Clin Pract 124:23–30

    Article  PubMed  Google Scholar 

  6. 6.

    Ferraro B, Galli F, Frei B, Kingdon E, Canestrari F, Rice-Evans C, Buoncristiani U, Davenport A, Moore KP (2003) Peroxynitrite-induced oxidation of plasma lipids is enhanced in stable hemodialysis patients. Kidney Int 63:2207–2213

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Davenport A (2014) How can dialyzer designs improve solute clearances for hemodialysis patients? Hemodial Int Suppl 1:S43–S47

    Article  Google Scholar 

  8. 8.

    Lim H-C, Lee S-J (2004) Flow control of a circular cylinder with O-rings. Fluid Dyn Res 35:107–122

    Article  Google Scholar 

  9. 9.

    Ronco C, Bowry SK, Brendolan A, Crepaldi C, Soffiati G, Fortunato A, Bordoni V, Granziero A, Torsello G, La Greca G (2002) Hemodialyzer: from macro-design to membrane nanostructure; the case of the FX-class of hemodialyzers. Kidney Int Suppl 80:126–142

    Article  Google Scholar 

  10. 10.

    Hirano A, Yamamoto K, Matsuda M, Ogawa T, Yakushiji T, Miyasaka T, Sakai K (2011) Evaluation of dialyzer jacket structure and hollow-fiber dialysis membranes to achieve high dialysis performance. Ther Apher Dial 15:66–74

    Article  PubMed  Google Scholar 

  11. 11.

    Yamamoto K, Matsuda M, Hirano A, Takizawa N, Iwashima S, Yakushiji T, Fukuda M, Miyasaka T, Sakai K (2009) Computational evaluation of dialysis fluid flow in dialyzers with variously designed jackets. Artif Organs 33:481–486

    Article  PubMed  Google Scholar 

  12. 12.

    Cheung AK, Rocco MV, Yan G, Leypoldt JK, Levin NW, Greene T, Agodoa L, Bailey J, Beck GJ, Clark W, Levey AS, Ornt DB, Schulman G, Schwab S, Teehan B, Eknoyan G (2006) Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study. J Am Soc Nephrol 17:546–555

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    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, Hemodialysis Study G (2002) Effect of dialysis dose and membrane flux in maintenance hemodialysis. New Engl J Med 347:2010–2019

    Article  PubMed  Google Scholar 

  14. 14.

    Sakai K, Matsuda M (2011) Solute removal efficiency and biocompatibility of the high-performance membrane - from engineering points of view. Contrib Nephrol 173:11–22

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Naka T, Haase M, Bellomo R (2010) ‘Super high-flux’ or ‘high cut-off’ hemofiltration and hemodialysis. Contrib Nephrol 166:181–189

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Buus NH, Rantanen JM, Krag SP, Andersen NF, Jensen JD (2015) Hemodialysis using high cut off filters in light chain cast nephropathy. Blood Purif 40:223–231

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Hutchison CA, Heyne N, Airia P, Schindler R, Zickler D, Cook M, Cockwell P, Grima D (2012) Immunoglobulin free light chain levels and recovery from myeloma kidney on treatment with chemotherapy and high cut-off haemodialysis. Nephrol Dial Transplant 27:3823–3828

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Premru V, Kovac J, Buturovic-Ponikvar J, Ponikvar R (2013) Some kinetic considerations in high cut-off hemodiafiltration for acute myoglobinuric renal failure. Ther Apher Dial 17:396–401

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Kneis C, Beck W, Boenisch O, Klefisch F, Deppisch R, Zickler D, Schindler R (2013) Elimination of middle-sized uremic solutes with high-flux and high-cut-off membranes: a randomized in vivo study. Blood Purif 36:287–294

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Girndt M, Fiedler R, Martus P, Pawlak M, Storr M, Bohler T, Glomb MA, Liehr K, Henning C, Templin M, Trojanowicz B, Ulrich C, Werner K, Zickler D, Schindler R (2015) High cut-off dialysis in chronic haemodialysis patients. Eur J Clin Invest 45:1333–1340

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Krieter DH, Canaud B (2003) High permeability of dialysis membranes: what is the limit of albumin loss? Nephrol Dial Transplant 18:651–654

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Ronco C, Orlandini G, Brendolan A, Lupi A, La Greca G (1998) Enhancement of convective transport by internal filtration in a modified experimental hemodialyzer: technical note. Kidney Int 54:979–985

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Hasegawa T, Nakai S, Masakane I, Watanabe Y, Iseki K, Tsubakihara Y, Akizawa T (2015) Dialysis fluid endotoxin level and mortality in maintenance hemodialysis: a nationwide cohort study. Am J Kidney Dis 65:899–904

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Ledebo I (2004) Ultrapure dialysis fluid: improving conventional and daily dialysis. Hemodial Int Int Symp Home Hemodial 8:159–166

    Article  Google Scholar 

  25. 25.

    Ronco C, Brendolan A, Lupi A, Metry G, Levin NW (2000) Effects of a reduced inner diameter of hollow fibers in hemodialyzers. Kidney Int 58:809–817

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Davenport A, Peters SA, Bots ML, Canaud B, Grooteman MP, Asci G, Locatelli F, Maduell F, Morena M, Nube MJ, Ok E, Torres F, Woodward M, Blankestijn PJ, Investigators HDFPP (2016) Higher convection volume exchange with online hemodiafiltration is associated with survival advantage for dialysis patients: the effect of adjustment for body size. Kidney Int 89:193–199

    Article  PubMed  Google Scholar 

  27. 27.

    Maduell F, Moreso F, Pons M, Ramos R, Mora-Macia J, Carreras J, Soler J, Torres F, Campistol JM, Martinez-Castelao A, Group ES (2013) High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol 24:487–497

    Article  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Maduell F, Arias-Guillen M, Fontsere N, Ojeda R, Rico N, Vera M, Elena M, Bedini JL, Wieneke P, Campistol JM (2014) Elimination of large uremic toxins by a dialyzer specifically designed for high-volume convective therapies. Blood Purif 37:125–130

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Meert N, Eloot S, Waterloos MA, Van Landschoot M, Dhondt A, Glorieux G, Ledebo I, Vanholder R (2009) Effective removal of protein-bound uraemic solutes by different convective strategies: a prospective trial. Nephrol Dial Transplant 24:562–570

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Davenport A (2008) Potential adverse effects of replacing high volume hemofiltration exchanges on electrolyte balance and acid-base status using the current commercially available replacement solutions in patients with acute renal failure. Int J Artif Organs 31:3–5

    CAS  PubMed  Google Scholar 

  31. 31.

    Kumar S, Khosravi M, Massart A, Potluri M, Davenport A (2013) Haemodiafiltration results in similar changes in intracellular water and extracellular water compared to cooled haemodialysis. Am J Nephrol 37:320–324

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Lee KH, Kim DJ, Min BG, Lee SH (2007) Polymeric nanofiber web-based artificial renal microfluidic chip. Biomed Microdevices 9:435–442

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Meijers BK, Bammens B, De Moor B, Verbeke K, Vanrenterghem Y, Evenepoel P (2008) Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int 73:1174–1180

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y (2006) Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney Int 69:1081–1087

  35. 35.

    Kandouz S, Mohamed AS, Zheng Y, Sandeman S, Davenport A (2016) Reduced protein bound uraemic toxins in vegetarian kidney failure patients treated by haemodiafiltration. Hemodial Int 20:610–617

    Article  PubMed  Google Scholar 

  36. 36.

    Krieter DH, Hackl A, Rodriguez A, Chenine L, Moragues HL, Lemke HD, Wanner C, Canaud B (2010) Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrol Dial Transplant 25:212–218

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Sirich TL, Luo FJ, Plummer NS, Hostetter TH, Meyer TW (2012) Selectively increasing the clearance of protein-bound uremic solutes. Nephrol Dial Transplant 27:1574–1579

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Luo FJ, Patel KP, Marquez IO, Plummer NS, Hostetter TH, Meyer TW (2009) Effect of increasing dialyzer mass transfer area coefficient and dialysate flow on clearance of protein-bound solutes: a pilot crossover trial. Am J Kidney Dis 53:1042–1049

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    De Smet R, Dhondt A, Eloot S, Galli F, Waterloos MA, Vanholder R (2007) Effect of the super-flux cellulose triacetate dialyser membrane on the removal of non-protein-bound and protein-bound uraemic solutes. Nephrol Dial Transplant 22:2006–2012

    Article  PubMed  Google Scholar 

  40. 40.

    Daugirdas JT, Greene T, Rocco MV, Kaysen GA, Depner TA, Levin NW, Chertow GM, Ornt DB, Raimann JG, Larive B, Kliger AS, Group FHNT (2013) Effect of frequent hemodialysis on residual kidney function. Kidney Int 83:949–958

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Krieter DH, Devine E, Korner T, Ruth M, Wanner C, Raine M, Jankowski J, Lemke HD (2017) Haemodiafiltration at increased plasma ionic strength for improved protein-bound toxin removal. Acta Physiol 219:510–520

    CAS  Article  Google Scholar 

  42. 42.

    Tao X, Thijssen S, Kotanko P, Ho CH, Henrie M, Stroup E, Handelman G (2016) Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study. Sci Rep 6:23389

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Hirsh SL, McKenzie DR, Nosworthy NJ, Denman JA, Sezerman OU, Bilek MM (2013) The Vroman effect: competitive protein exchange with dynamic multilayer protein aggregates. Colloids Surf B Biointerfaces 103:395–404

    CAS  Article  PubMed  Google Scholar 

  44. 44.

    Clark WR, Macias WL, Molitoris BA, Wang NH (1995) Plasma protein adsorption to highly permeable hemodialysis membranes. Kidney Int 48:481–488

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Tessitore N, Lapolla A, Arico NC, Poli A, Gammaro L, Bassi A, Bedogna V, Corgnati A, Reitano R, Fedele D, Lupo A (2004) Effect of protein leaking BK-F PMMA-based hemodialysis on plasma pentosidine levels. J Nephrol 17:707–714

    PubMed  Google Scholar 

  46. 46.

    Galli F, Benedetti S, Buoncristiani U, Piroddi M, Conte C, Canestrari F, Buoncristiani E, Floridi A (2003) The effect of PMMA-based protein-leaking dialyzers on plasma homocysteine levels. Kidney Int 64:748–755

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Ronco C, Brendolan A, Winchester JF, Golds E, Clemmer J, Polaschegg HD, Muller TE, La Greca G, Levin NW (2001) First clinical experience with an adjunctive hemoperfusion device designed specifically to remove beta(2)-microglobulin in hemodialysis. Blood Purif 19:260–263

    CAS  Article  PubMed  Google Scholar 

  48. 48.

    Meyer TW, Peattie JW, Miller JD, Dinh DC, Recht NS, Walther JL, Hostetter TH (2007) Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. J Am Soc Nephrol 18:868–874

    CAS  Article  PubMed  Google Scholar 

  49. 49.

    Sandeman SR, Howell CA, Phillips GJ, Zheng Y, Standen G, Pletzenauer R, Davenport A, Basnayake K, Boyd O, Holt S, Mikhalovsky SV (2014) An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis. J Mater Sci Mater Med 25:1589–1597

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Tijink MS, Wester M, Glorieux G, Gerritsen KG, Sun J, Swart PC, Borneman Z, Wessling M, Vanholder R, Joles JA, Stamatialis D (2013) Mixed matrix hollow fiber membranes for removal of protein-bound toxins from human plasma) Biomaterials 34:7819–7828

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Betjes MG, Hoekstra FM, Klepper M, Postma SM, Vaessen LM (2004) Vitamin E-coated dialyzer membranes downregulate expression of monocyte adhesion and co-stimulatory molecules. Blood Purif 22:510–517

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Yang SK, Xiao L, Xu B, Xu XX, Liu FY, Sun L (2014) Effects of vitamin E-coated dialyzer on oxidative stress and inflammation status in hemodialysis patients: a systematic review and meta-analysis. Renal Fail 36:722–731

    CAS  Article  Google Scholar 

  53. 53.

    Islam MS, Hassan ZA, Chalmin F, Vido S, Berrada M, Verhelst D, Donnadieu P, Moranne O, Esnault VL (2016) Vitamin E-coated and heparin-coated dialyzer membranes for heparin-free hemodialysis: a multicenter, randomized, crossover trial. Am J Kidney Dis 68:752–762

    CAS  Article  PubMed  Google Scholar 

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Correspondence to Andrew Davenport.

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Funding for this study was provided by the Royal Free Hospital. Kamonwan Tangvoraphonkchai was in receipt of a scholarship from the International Society of Nephrology

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1. d; 2. b; 3. d; 4. a; 5. d

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Tangvoraphonkchai, K., Davenport, A. Enhancing dialyser clearance—from target to development. Pediatr Nephrol 32, 2225–2233 (2017). https://doi.org/10.1007/s00467-017-3647-y

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Key words

  • Dialyser
  • Haemodialysis
  • Haemodiafiltration
  • Adsorption
  • Absorption