Hemodiafiltration History, Technology, and Clinical Results

      Hemodiafiltration (HDF) is an extracorporeal renal-replacement technique using a highly permeable membrane, in which diffusion and convection are conveniently combined to enhance solute removal in a wide spectrum of molecular weights. In this modality, ultrafiltration exceeds the desired fluid loss in the patient, and replacement fluid must be administered to achieve the target fluid balance. Over the years, various HDF variants have emerged, including acetate-free biofiltration, high-volume HDF, internal HDF, paired-filtration dialysis, middilution HDF, double high-flux HDF, push-pull HDF, and online HDF. Recent technology has allowed online production of large volumes of microbiologically ultrapure fluid for reinfusion, greatly simplifying the practice of HDF. Several advantages of HDF over purely diffusive hemodialysis techniques have been described in the literature, including a greater clearance of urea, phosphate, β2-microglobulin and other larger solutes, reduction in dialysis hypotension, and improved anemia management. Although randomized controlled trials have failed to show a survival benefit of HDF, recent data from large observational studies suggest a positive effect of HDF on survival. This article provides a brief review of the history of HDF, the various HDF techniques, and summary of their clinical effects.

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        • Alwall N.
        On the artificial kidney.
        Acta Med Scand. 1947; 128: 317-321
        • Kolff W.J.
        First clinical experience with the artificial kidney.
        Ann Intern Med. 1965; 62: 608-612
        • Henderson L.W.
        • Besarab A.
        • Michaels A.
        • et al.
        Blood purification by UF and fluid replacement (diafiltration).
        Trans Am Soc Artif Intern Organs. 1967; 17: 216-221
        • Henderson L.W.
        • Colton C.K.
        • Ford C.
        Kinetics of HDF.
        J Lab Clin Med. 1975; 85: 372-375
        • Maher J.F.
        • Schreiner G.E.
        • Waters T.J.
        Successful intermittent hemo-dialysis-longest reported maintenance of life in true oliguria (181 days).
        Trans Am Soc Artif Itern Organs. 1960; 6: 123-126
        • Bergstrom J.
        UF without dialysis for removal of fluid and solutes in uremia.
        Clin Nephrol. 1978; 9: 156-161
        • Babb A.L.
        • Farrel P.C.
        • Uvelli D.A.
        • et al.
        Hemodialyzer evaluation by examination of solute molecular spectra.
        Trans Am Soc Artif Intern Organs. 1972; 18: 98-105
        • Babb A.L.
        • Strand M.J.
        • Uvelli D.A.
        • et al.
        Quantitative description of dialysis treatment: A dialysis index.
        Kidney Int. 1975; 7: 23-28
        • Henderson L.W.
        Biophysics of UF and hemofiltration.
        in: Maher J.F. Replacement of Renal Function by Dialysis A Text-book of Dialysis. (ed 3). Kluwer Academic Publishers, Dordrecht, The Netherlands1989: 300-326
        • Miller J.
        • von Albertini B.
        • Gardner B.
        • et al.
        Technical aspects of high flux hemodiafiltration for adequate short (under 2 hours) treatment.
        Trans Am Soc Artif Intern Organs. 1984; 30: 377-381
        • Leber H.
        • Wizemann V.
        • Goubeaud G.
        • et al.
        Simultaneous hemofiltration/hemodialysis: An effective alternative to hemofiltration and conventional hemodialysis in the treatment of uremic patients.
        Clin Nephrol. 1978; 9: 115-121
        • Kunitomo T.
        • Kirkwood R.G.
        • Kumazawa S.
        • et al.
        Clinical evaluation of postdilution dialysis with a combined ultrafiltration (UF)–hemodialysis (HD) system.
        Trans Am Soc Artif Intern Organs. 1978; 24: 169-177
        • Ronco C.
        • Brendolan A.
        • Crepaldi C.
        • et al.
        Blood and dialysate flow distributions in hollow-fiber hemodialyzers analyzed by computerized helical scanning technique.
        J Am Soc Nephrol. 2002; 13: S53-S61
        • Maduell F.
        Hemodial Int. 2005; 9: 47-55
        • Pedrini L.A.
        • Cozzi G.
        • Faranna P.
        • et al.
        Transmembrane pressure modulation in high-volume mixed hemodiafiltration to optimize efficiency and minimize protein loss.
        Kidney Int. 2006; 69: 573-579
        • Canaud B.
        • Levesque R.
        • Krieter D.
        • et al.
        On-line hemodiafiltration as routine treatment of end-stage renal failure: Why pre- or mixed dilution mode is necessary in on-line hemodiafiltration today?.
        Blood Purif. 2004; 22: 40-48
        • Fiore G.B.
        • Guadagni G.
        • Lupi A.
        • et al.
        A new semiempirical mathematical model for prediction of internal filtration in hollow fiber hemodialyzers.
        Blood Purif. 2006; 24: 555-568
        • Mandolfo S.
        • Corsi A.
        • Wratten M.L.
        • et al.
        Evaluation of hygiene and safety controls for on-line paired hemodiafiltration (PHF).
        Int J Artif Organs. 2006; 29: 160-165
        • Santoro A.
        • Conz P.A.
        • De Cristofaro V.
        • et al.
        Mid-dilution: The perfect balance between convection and diffusion.
        Contrib Nephrol. 2005; 149: 107-114
        • Miwa M.
        • Shinzato T.
        Push/pull hemodiafiltration: technical aspects and clinical effectiveness.
        Artif Organs. 1999; 23: 1123-1126
        • Ledebo I.
        On-line preparation of solutions for dialysis: Practical aspects versus safety and regulations.
        J Am Soc Nephrol. 2002; 13: S78-S83
        • Canaud B.
        • Bosc J.Y.
        • Leray-Moragues H.
        • et al.
        On-line haemodiafiltration.
        Nephrol Dial Transplant. 2000; 5: S60-S67
        • Guth H.J.
        • Gruska S.
        • Kraatz G.
        On-line production of ultrapure substitution fluid reduces TNF-alpha- and IL-6 release in patients on hemodiafiltration therapy.
        Int J Artif Organs. 2003; 26: 181-187
        • Canaud B.
        • Bragg-Gresham J.L.
        • Marshall M.R.
        • et al.
        Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS.
        Kidney Int. 2006; 69: 2087-2093
        • Blankestijn P.J.
        • Vos P.F.
        • Rabelink T.J.
        • et al.
        High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients.
        J Am Soc Nephrol. 1995; 5: 1703-1708
        • Lin C.L.
        • Huang C.C.
        • Yu C.C.
        • et al.
        Reduction of advanced glycation end product levels by on-line hemodiafiltration in long-term hemodialysis patients.
        Am J Kidney Dis. 2003; 42: 524-531
        • Kerr P.B.
        • Argiles A.
        • Flavier J.L.
        • et al.
        Comparison of hemodialysis and hemodiafiltration: A long-term longitudinal study.
        Kidney Int. 1992; 41: 1035-1040
        • Lornoy W.
        • De Meester J.
        • Becaus I.
        • et al.
        Impact of convective flow on phosphorus removal in maintenance hemodialysis patients.
        J Ren Nutr. 2006; 16: 47-53
        • Lin C.L.
        • Yang C.W.
        • Chiang C.C.
        • et al.
        Long-term on-line hemodiafiltration reduces predialysis beta-2-microglobulin levels in chronic hemodialysis patients.
        Blood Purif. 2001; 19: 301-307
        • Rabindranath K.S.
        • Strippoli G.F.
        • Roderick P.
        • et al.
        Comparison of hemodialysis, hemofiltration, and acetate-free biofiltration for ESRD: Systematic review.
        Am J Kidney Dis. 2005; 45: 437-447
        • Maduell F.
        • Navarro V.
        • Cruz M.C.
        • et al.
        Osteocalcin and myoglobin removal in on-line hemodiafiltration versus low- and high-flux hemodialysis.
        Am J Kidney Dis. 2002; 40: 582-589
        • Bammens B.
        • Evenepoel P.
        • Verbeke K.
        • et al.
        Removal of the protein-bound solute p-cresol by convective transport: A randomized crossover study.
        Am J Kidney Dis. 2004; 44: 278-285
        • Gonella M.
        • Calabrese G.
        • Mengozzi A.
        • et al.
        The achievement of normal homocysteinemia in regular extracorporeal dialysis patients.
        J Nephrol. 2004; 17: 411-413
        • Wiesholzer M.
        • Harm F.
        • Hauser A.C.
        • et al.
        Inappropriately high plasma leptin levels in obese haemodialysis patients can be reduced by high flux haemodialysis and haemodiafiltration.
        Clin Sci (Lond). 1998; 94: 431-435
        • Donauer J.
        • Schweiger C.
        • Rumberger B.
        • et al.
        Reduction of hypotensive side effects during online-haemodiafiltration and low temperature haemodialysis.
        Nephrol Dial Transplant. 2003; 18: 1616-1622
        • Locatelli F.
        • Marcelli D.
        • Conte F.
        • et al.
        Comparison of mortality in ESRD patients on convective and diffusive extracorporeal treatments.
        Kidney Int. 1999; 55: 286-293
        • Sitter T.
        • Bergner A.
        • Schiffl H.
        Dialysate related cytokine induction and response to recombinant human erythropoietin in haemodialysis patients.
        Nephrol Dial Transplant. 2000; 15: 1207-1211
        • Lin C.L.
        • Huang C.C.
        • Chang C.T.
        • et al.
        Clinical improvement by increased frequency of on-line hemodialfiltration.
        Ren Fail. 2001; 23: 193-206
        • Ward R.A.
        • Schmidt B.
        • Hullin J.
        • et al.
        A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study.
        J Am Soc Nephrol. 2000; 11: 2344-2350
        • Ursino M.
        • Coli L.
        • Magosso E.
        • et al.
        A mathematical model for the prediction of solute kinetics, osmolarity and fluid volume changes during hemodiafiltration with on-line regeneration of ultrafiltrate (HFR).
        Int J Artif Organs. 2006; 29: 1031-1040
        • Yamamoto K.
        • Hiwatari M.
        • Kohori F.
        • et al.
        Membrane fouling and dialysate flow pattern in an internal filtration-enhancing dialyzer.
        J Artif Organs. 2005; 8: 198-205