Mid-dilution hemodiafiltration (MID) is a dialytic technique that might improve systemic inflammation of patients in chronic hemodialysis (HD) by increasing substitution volumes. To verify this hypothesis, we performed a prospective cross-over study comparing the effect on inflammatory biomarkers of higher convection by MID versus standard convection by post-dilution hemodiafiltration (HDF). Patients under chronic HD were therefore treated by MID and HDF by crossover design. Each treatment period lasted 4 months, with 1 month of wash-out where patients were treated by HD, for a total of 9 months. Primary outcome was the change of serum pre-dialytic C-Reactive Protein (CRP), interleukin 6 (IL-6), IL-1, IL-10, transforming growth factor-β (TGF-β), tumor necrosis factor-α, albumin and pre-albumin. Samples were obtained monthly. Ten HD patients were enrolled (age: 64.9 ± 12.6 years; 70% males; dialytic vintage: 10.6 [2.7–16.2] years). Mean convection volume was 40.1 ± 2.5 L/session in MID and 20.1 ± 2.6 L/session in HDF. A significant reduction of β2-Microglobulin was detected as a result of either treatment. In MID, CRP decreased from 11.3 (3.2–31.0) to 3.1 (1.4–14.4) mg/L (p = 0.007), IL-6 from 12.7 (5.0–29.7) to 8.3 (4.4–14.0) pg/mL (p = 0.003), and TGF-β from 10.6 (7.4–15.6) to 7.4 (5.9–9.3) ng/mL (p = 0.001). A significant reduction of CRP from 8.5 (3.2–31.0) to 4.6 (3.2–31.0) mg/L was also detected in HDF (p = 0.037), whereas no significant reduction of IL-6 (p = 0.147) and TGF-β (p = 0.094) was found. Percentage reduction of IL-6 correlated with mean convective volume in HDF (R = 0.666; p = 0.036) and in MID (R = 0.760; p = 0.020). Therefore, MID and HDF are associated with an attenuation of inflammatory pattern that is correlated with a high convective volume.

1.
Nordio M, Limido A, Maggiore U, et al: Survival in patients treated by long-term dialysis compared with the general population. Am J Kidney Dis 2012; 59: 819–828.
2.
Wang AY, Ninomiya T, Al-Kahwa A, Perkovic V, Gallagher MP, Hawley C, Jardine, MJ: Effect of hemodiafiltration or hemofiltration compared with hemodialysis on mortality and cardiovascular disease in chronic kidney failure: a systematic review and meta-analysis of randomized trials. Am J Kidney Dis 2014; 63: 968–978.
3.
Maduell F, Moreso F, Pons M, Ramos R, Mora-Macià J, Carreras J et al: High-efficiency post-dilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol 2013; 24: 487–97.
4.
Grooteman MP, van den Dorpel MA, Bots ML, Penne EL, van der Weerd NC, Mazairac AH et al; CONTRAST investigators: Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes. J Am Soc Nephrol 2012; 23: 1087–1096.
5.
Ok E, Asci G, Toz H, Ok ES, Kircelli F, Yilmaz M, et al; Turkish Online Haemodiafiltration Study: Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish OL-HDF Study. Nephrol Dial Transplant 2013; 28: 192–202.
6.
Canaud B, Bragg-Gresham JL, Marshall MR, Desmeules S, Gillespie BW, Depner T, et al: Mortality risk for patients receiving haemodiafiltration versus hemodialysis: European results from the DOPPS. Kidney Int 2006; 69: 2087–2093.
7.
Peters SA, Bots ML, Canaud B, Davenport A, Grooteman MP, Kircelli F, et al; HDF Pooling Project Investigators: Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials. Nephrol Dial Transplant 2016; 31: 978–984.
8.
Kawanishi H: Is there enough evidence to prove that hemodiafiltration is superior? Blood Purif 2018; 46: 3–6.
9.
Ronco C: Hemodiafiltration: technical and clinical issues. Blood Purif 2015; 40(suppl 1): 2–11.
10.
de Roij van Zuijdewijn CL, Nubé MJ, ter Wee PM, Blankestijn PJ, Lévesque R, van den Dorpel MA, Bots ML, Grooteman MP: Treatment time or convection volume in HDF: what drives the reduced mortality risk? Blood Purif 2015; 40: 53–58.
11.
Locatelli F, Martin-Malo A, Hannedouche T, Loureiro A, Papadimitriou M, Wizemann V, et al; Membrane Permeability Outcome (MPO) Study Group: Effect of membrane permeability on survival of hemodialysis patients. J Am Soc Nephrol 2009; 20: 645–654.
12.
Panichi V, Rizza GM, Paoletti S, Bigazzi R, Aloisi M, Barsotti G,et al; RISCAVID Study Group: Chronic inflammation and mortality in hemodialysis: effect of different renal replacement therapies. Results from the RISCAVID study. Nephrol Dial Transplant 2008; 23: 2337–2343.
13.
Panichi V, Manca-Rizza G, Paoletti S, Taccola D, Consani C, Filippi C, et al: Effects on inflammatory and nutritional markers of haemodiafiltration with online regeneration of ultrafiltrate (HFR) vs online haemodiafiltration: a cross-over randomized multicentre trial. Nephrol Dial Transplant 2006; 21: 756–762.
14.
Borrelli S, Minutolo R, De Nicola L, De Simone E, De Simone W, Zito B, et al: Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: a multicenter longitudinal study. Hemodial Int 2014; 18: 758–766.
15.
Meert N, Eloot S, Schepers E, Lemke HD, Dhondt A, Glorieux G, et al: Comparison of removal capacity of two consecutive generations of high-flux dialysers during different treatment modalities. Nephrol Dial Transplant 2011; 26: 2624–2630.
16.
den Hoedt CH, Bots ML, Grooteman MP, van der Weerd NC, Mazairac AH, Penne EL, et al; CONTRAST Investigators: Online hemodiafiltration reduces systemic inflammation compared to low-flux hemodialysis. Kidney Int 2014; 86: 423–432.
17.
Canaud B, Barbieri C, Marcelli D, Bellocchio F, Bowry S, Mari F, et al: Optimal convection volume for improving patient outcomes in an international incident dialysis cohort treated with online hemodiafiltration. Kidney Int 2015; 88: 1108–1116.
18.
Molina P, Vizcaíno B, Molina MD, Beltrán S, González-Moya M, Mora A, et al: The effect of high-volume online haemodiafiltration on nutritional status and body composition: the ProtEin Stores prEservaTion (PESET) study. Nephrol Dial Transplant 2018; 33: 1223–1235.
19.
Tattersall JE, Ward RA; EUDIAL group: Online haemodiafiltration: definition, dose quantification and safety revisited. Nephrol Dial Transplant 2013; 28: 542–550.
20.
Marcelli D, Scholz C, Ponce P, Sousa T, Kopperschmidt P, Grassmann A, et al: High-volume post-dilution hemodiafiltration is a feasible option in routine clinical practice. Artif Organs 2014; 39: 142–149.
21.
Robinson BM, Akizawa T, Jager KJ, Kerr PG, Saran R, Pisoni RL: Factors affecting outcomes in patients reaching end-stage kidney disease worldwide: differences in access to renal replacement therapy, modality use, and haemodialysis practices. Lancet 2016; 388: 294–306.
22.
Santoro A, Conz PA, De Cristofaro V, Acquistapace I, Gaggi R, Ferramosca E, et al: Mid-dilution: the perfect balance between convection and diffusion. Contrib Nephrol 2005; 149: 107–114.
23.
Krieter DH, Falkenhain S, Chalabi L, et al: Clinical cross-over comparison of mid-dilution hemodiafiltration using a novel dialyzer concept and post-dilution hemodiafiltration. Kidney Int 2005; 67: 349–356.
24.
Krieter DH, Falkenhain S, Chalabi L, Collins G, Lemke HD, Canaud B: Mid-dilution on-line haemodiafiltration in a standard dialyzer configuration. Nephrol Dial Transplant 2005; 20: 155–160.
25.
Santoro A, Ferramosca E, Mancini E, Monari C, Varasani M, Sereni L, et al: Reverse mid-dilution: new way to remove small and middle molecules as well as phosphate with high intrafilter convective clearance. Nephrol Dial Transplant 2007; 22: 2000–2005.
26.
Feliciani A, Riva MA, Zerbi S, Ruggiero P, Plati AR, Cozzi G, et al: New strategies in haemodiafiltration (HDF): prospective comparative analysis between on-line mixed HDF and mid-dilution HDF. Nephrol Dial Transplant 2007; 22: 1672–1679.
27.
Pedrini LA, Feliciani A, Zerbi S, Cozzi G, Ruggiero P: Optimization of mid-dilution haemodiafiltration: technique and performance. Nephrol Dial Transplant 2009; 24: 2816–2824.
28.
Mandolfo S, Borlandelli S, Imbasciati E, Badalamenti S, Graziani G, Sereni L, et al: Pilot study to assess increased dialysis efficiency in patients with limited blood flow rates due to vascular access problems. Hemodial Int 2008; 12: 55–61.
29.
The EBPG Expert Group on Haemodialysis. European Best Practice Guidelines for Haemodialysis: part 1. Nephrol Dial Transplant 2002; 17(suppl 7):S45–S46
30.
Conover WJ: Practical Nstatistics. New York, Wiley, 1971.
31.
Maduell F, Arias M, Vera M, Fontseré N, Blasco M, Barros X, et al: Mid-dilution hemodiafiltration: a comparison with pre- and postdilution modes using the same polyphenylene membrane. Blood Purif 2009; 28: 268–274.
32.
Memoli B, Minutolo R, Bisesti V, Postiglione L, Conti A, Marzano L, et al; Collaborative Study Group on SMC Membrane. Changes of serum albumin and C-reactive protein are related to changes of interleukin-6 release by peripheral blood mononuclear cells in hemodialysis patients treated with different membranes. Am J Kidney Dis 2002; 39: 266–273.
33.
Calò LA, Naso A, Carraro G, Wratten ML, Pagnin E, Bertipaglia L, et al: Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients. Nephrol Dial Transplant 2007; 22: 1413–1419.
34.
Vilar E, Fry AC, Wellsted D, Tattersall JE, Greenwood RN, Farrington K: Long-term outcomes in online hemodiafiltration and high-flux hemodialysis: a comparative analysis. Clin J Am Soc Nephrol 2009; 4: 1944–1953.
35.
Penne EL, van der Weerd NC, Blankestijn PJ, van den Dorpel MA, Grooteman MP, Nubé MJ, et al: Role of residual kidney function and convective volume on change in beta2-microglobulin levels in hemodiafiltration patients. Clin J Am Soc Nephrol 2010; 5: 80–86.
36.
Panichi V, Scatena A, Rosati A, Giusti R, Ferro G, Malagnino E, et al: High-volume online haemodiafiltration improves erythropoiesis-stimulating agent (ESA) resistance in comparison with low-flux bicarbonate dialysis: results of the REDERT study. Nephrol Dial Transplant 2015; 30: 682–689.
37.
Mid-HDF Randomized Controlled Study on Outcome (MILESTONE). www.clinicaltrials.gov/ct2/show/NCT01693354.
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