American Journal of Kidney Diseases

The Effect of On-line High-flux Hemofiltration Versus Low-flux Hemodialysis on Mortality in Chronic Kidney Failure: A Small Randomized Controlled Trial


      Given the paucity of prospective randomized controlled trials assessing comparative performances of different dialysis techniques, we compared on-line high-flux hemofiltration (HF) with ultrapure low-flux hemodialysis (HD), assessing survival and morbidity in patients with end-stage renal disease (ESRD).

      Study Design

      An investigator-driven, prospective, multicenter, 3-year-follow-up, centrally randomized study with no blinding and based on the intention-to-treat principle.

      Setting & Participants

      Prevalent patients with ESRD (age, 16 to 80 years; vintage > 6 months) receiving renal replacement therapy at 20 Italian dialysis centers.


      Patients were centrally randomly assigned to HD (n = 32) or HF (n = 32).

      Outcomes & Measurements

      All-cause mortality, hospitalization rate for any cause, prevalence of dialysis hypotension, standard biochemical indexes, and nutritional status. Analyses were performed using the multivariate analysis of variance and Cox proportional hazard method.


      There was significant improvement in survival with HF compared with HD (78%, HF versus 57%, HD) at 3 years of follow-up after allowing for the effects of age (P = 0.05). End-of-treatment Kt/V was significantly higher with HD (1.42 ± 0.06 versus 1.07 ± 0.06 with HF), whereas β2-microglobulin levels remained constant in HD patients (33.90 ± 2.94 mg/dL at baseline and 36.90 ± 5.06 mg/dL at 3 years), but decreased significantly in HF patients (30.02 ± 3.54 mg/dL at baseline versus 23.9 ± 1.77 mg/dL; P < 0.05). The number of hospitalization events for each patient was not significantly different (2.36 ± 0.41 versus 1.94 ± 0.33 events), whereas length of stay proved to be significantly shorter in HF patients compared with HD patients (P < 0.001). End-of-treatment body mass index decreased in HD patients, but increased in HF patients. Throughout the study period, the difference in trends of intradialytic acute hypotension was statistically significant, with a clear decrease in HF (P = 0.03).


      This is a small preliminary intervention study with a high dropout rate and problematic generalizability.


      On-line HF may improve survival independent of Kt/V in patients with ESRD, with a significant decrease in plasma β2-microglobulin levels and increased body mass index. A larger study is required to confirm these results.

      Index Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • US Renal Data System
        USRDS 2002 Annual Data Report: Atlas of end-stage renal disease in the United States, Bethesda, MD, USA, 2002.
        Am J Kidney Dis. 2003; 41: S41-S210
        • Locatelli F.
        • Marcelli M.
        • Conte F.
        • et al.
        Comparison of mortality in ESRD patients on convective and diffusive extracorporeal treatments.
        Kidney Int. 1999; 55: 286-293
        • Mc Donald S.P.
        • Craig J.C.
        • Australian and New Zealand Pediatric Nephrology Association
        Long-term survival of children with end-stage renal disease.
        N Engl J Med. 2004; 350: 2654-2662
        • Cheung A.K.
        • Rocco M.V.
        • Yan G.
        • et al.
        Serum beta-2 microglobulin levels predict mortality in dialysis patients: Results of the HEMO Study.
        J Am Soc Nephrol. 2006; 17: 546-555
        • 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
        • Eknoyan G.
        • Beck G.J.
        • Cheung A.K.
        • et al.
        Effect of dialysis dose and membrane flux in maintenance hemodialysis.
        N Engl J Med. 2002; 347: 2000-2019
        • Kooman P.K.
        • van der Sande F.M.
        • Leunissen K.M.L.
        Predilution haemofiltration.
        Nephrol Dial Transplant. 2002; 17: 171-172
        • Nakagawa S.
        Multifactorial evaluation of hemofiltration therapy in comparison with conventional hemodialysis.
        Artif Organs. 1980; 4: 94-102
        • Wizeman V.
        • Lotz C.
        • Techert F.
        • et al.
        On-line haemodiafiltration versus low-flux haemodialysis.
        Nephrol Dial Transplant. 2000; 15: S143-S148
        • Henderson L.
        • Besarb A.
        • Michael A.
        • Bluemle L.W.
        Blood purification by ultrafiltration and fluid replacement/diafiltration.
        Trans Am Soc Artif Intern Organs. 1967; 16: 216-222
        • Schaefer K.
        • von Herrach D.
        Hemofiltration in the past and present.
        Contrib Nephrol. 1992; 96: 64-76
        • Quellhorst E.
        Cardiovascular problems in end-stage renal failure: Haemofiltration.
        Contrib Nephrol. 1985; 78: 212-230
        • Altieri P.
        • Sorba G.B.
        • Bolasco P.G.
        • et al.
        On-line predilution hemofiltration versus ultrapure high-flux hemodialysis: A multicenter prospective study in 23 patients.
        Blood Purif. 1997; 15: 169-181
        • Keshaviah P.
        • Collins A.
        • Berkseth R.
        • et al.
        Adequacy, benefits, complications, dose and efficacy of filtration—The Minneapolis experience.
        J Blood Purif. 1984; 2: 149-157
        • Cheung A.K.
        • Levin N.W.
        • Greene T.
        • et al.
        Effects of high-flux hemodialysis on clinical outcomes: Results of the HEMO Study.
        J Am Soc Nephrol. 2003; 14: 3251-3263
        • Jirka T.
        • Cesare S.
        • Di Benedetto A.
        • et al.
        The impact of on-line hemodiafiltration (HDF) on patient survival: Results from a large network database.
        Nephrol Dial Transplant. 2005; 20: S18-S19
        • Santoro A.
        • Mancini E.
        • Zucchelli P.
        The impact of hemofiltration on the systemic cardiovascular response.
        Nephrol Dial Transpl. 2000; 15: S49-S54
        • Altieri P.
        • Sorba G.
        • Bolasco P.
        • et al.
        Comparison between hemofiltration and hemodiafiltration in a long-term prospective cross-over study.
        J Nephrol. 2004; 17: 414-422
        • Koch M.
        • Thomas B.
        • Tschope W.
        • Ritz E.
        Survival and predictors of death in dialyzed diabetic patients.
        Diabetologia. 1993; 36: 1113-1117
        • Shoji T.
        • Tsubakihara Y.
        • Fujii M.
        • Imai E.
        Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in haemodialysis patients.
        Kidney Int. 2004; 66: 1212-1220
        • Locatelli F.
        • DiFilippo S.
        • Manzoni C.
        Removal of small and middle molecules by convective techniques.
        Nephrol Dial Transplant. 2000; 15: S37-S44
        • Van Kuijk W.H.M.
        • Hillion D.
        • Saviou C.
        • Leunissen K.M.L.
        Critical role of extracorporeal blood temperature in the hemodynamic response during hemofiltration.
        J Am Soc Nephrol. 1997; 8: 949-955
        • Bergstrom J.
        • Asaba H.
        • Fuerst P.
        • Oules R.
        Dialysis ultrafiltration and blood pressure.
        Proc EDTA. 1976; 13: 293-300
        • Maggiore Q.
        • Pizzarelli F.
        • Sisca S.
        • et al.
        Blood temperature and vascular stability during hemodialysis and hemofiltration.
        Trans Am Soc Artif Intern Organs. 1982; 28: 523-527
        • Schaefer K.
        • von Herrath D.
        Hemofiltration in the past and present.
        Contrib Nephrol. 1992; 96: 64-76
        • Genovesi S.
        • Bracchi O.
        • Fabbrini P.
        • et al.
        Differences in heart rate variability during hemodialysis and hemofiltration.
        Nephrol Dial Transplant. 2007; 22: 2256-2262
        • National Kidny Foundation
        K/DOQI Clinical Practice Guidelines for Hemodialysis Adequacy: Update 2000.
        Am J Kidney Dis. 2001; 37: S7-S64
        • Maduell F.
        • Navarro V.
        • Torregrosa E.
        • et al.
        Change from three times a week on-line hemodiafiltration to short daily on-line hemodiafiltration.
        Kidney Int. 2003; 64: 305-313
        • Bossola M.
        • Tazza L.
        • Giungi S.
        • Lucani G.
        Anorexia in hemodialysis patients: An update.
        Kidney Int. 2006; 70: 417-422
        • Schiffl H.
        • D'Agostini B.
        • Held E.
        Removal of beta2-microglobulin by hemodialysis and hemofiltration: A four year follow up.
        Biomater Artif Cells Immobilisation Biotechnol. 1992; 20: 1223-1232
        • Quellhorst E.
        • Hildebrand U.
        • Solf A.
        Long-term morbidity: Hemofiltration vs hemodialysis.
        Contrib Nephrol. 1995; 113: 110-111
        • Rabindranath K.S.
        • Strippoli G.F.M.
        • Roderick P.
        • Wallace S.
        • MacLeod A.
        • Daly C.
        Comparison of hemodialysis, hemofiltration and acetate-free biofiltration for ESRD: Systematic review.
        Am J Kidney Dis. 2005; 45: 437-447
        • Schiffl H.
        Hemodiafiltration does not increase the risk for mortality in ESRD.
        Am J Kidney Dis. 2005; 46: 167-168
        • Locatelli F.
        Comparison of hemodialysis, hemodiafiltration, and hemofiltration: Systematic review or systematic error?.
        Am J Kidney Dis. 2005; 46: 787-788

      Linked Article

      • “Artificial” Hemodialysis Versus “Natural” Hemofiltration
        American Journal of Kidney DiseasesVol. 52Issue 3
        • Preview
          Because the native kidney is a filter and does not engage in the process of dialysis, long-held beliefs in the superiority of blood filtration for eliminating uremic toxins have rarely been challenged. What could be better than the divine prototype?
        • Full-Text
        • PDF
      • Effect of Hemofiltration on Mortality: No Definite Answer Yet
        American Journal of Kidney DiseasesVol. 53Issue 3
        • Preview
          With interest, we read the report by Santoro et al.1 They reported an impressive age-adjusted 55% decrease in all-cause mortality for patients treated with hemofiltration. This result was achieved although the hemofiltration group had less favorable baseline characteristics and sample size was very small. However, a considerable number of dropouts occurred.
        • Full-Text
        • PDF