1. Alejandro Martín Malo Hosp Univers Reina Sofía CORDOBA "¿Qué aportan las nuevas técnicas de Hemodiálisis a la supervivencia del paciente?”

2. Demographic characteristics Comorbidity Age Gender Race Diabetes (30%) CV disease (76%) Nutritional status Vascular Access Dialysate purity Treatment complic ALTERNATIVES TO CONVENTIONAL HD High-flux membranes Longer dialysis Short daily HD Long Nocturnal HD High convective transport On-line hemodiafiltration

3. HEMO study Alta versus baja permeabilidad 3.7 años en HD p<0.05 Eknoyan G et al. N Engl J Med 2002; 347: 2010-19

4. 70 80 90 100 06121824303642485460 % Survival 70 80 90 Time to cardiac death by Flux groups Adjusted RR for High-flux: 0.78 (0.63 - 0.97) p= 0.03 High-Flux Low-Flux Eknoyan G et al. N Engl J Med 2002; 347: 2010-19 Follow-up time [months]

5. P=0.0320 MPO Supervivencia en pacientes con Albumina<4g/dl n=492 Survival of patients (%) 1.0 0.8 0,6 0.4 0.2 0.0 High-flux Low-flux Months 0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90 J Am Soc Nephrol 20:645,2009

6. Geographical variability affect outcomes of incident HD patients. A Martin-Malo et al J Nephrol 26:119-28, 2013 In Cox proportional hazards model, higher mortality risk was estimated for the Northern European patients after adjustment for age, gender, membrane permeability, comorbidity index and vascular access. Only some factors can be modified in attempts to lower the mortality risk in this geographical area.

7. Cardiovascular event-free survival in subgroups analysis Asci G et al. J Am Soc Nephrol 2013;24:1014-23 Patients with AV fistula Months High-flux HD Low-flux HD Cumulative Survival p=0.02 Posthoc analyses suggest that high-flux HD may benefit patients with an arteriovenous fistula and patients with diabetes

8. Am J Kidney Dis. 2015; 66(5):823-83 Dialysis using high-flux membranes reduced cardiovascular mortality compared to dialysis with low-flux membranes.

9. Guideline 5: Hemodialysis Membranes 5.1 We recommend the use of biocompatible, either high or low flux hemodialysis membranes for intermittent hemodialysis. (1B) High-flux dialyzers should be used preferentially. In locations with cost restraints, patients with dia- betes, lower serum albumin, or longer dialysis vin- tage should be considered a priority for selection of High-flux dialyzers

10. In-Center Hemodialysis Six Times per Week versus Three Times per Week The FHN Trial Group. N Engl J Med 363:2287-2300, 2010. the randomization was troublesome (65 facilities >4 years were needed to enroll 224 patients).

11. Forest plot of time to first access repair, access loss, or access hospitalization by trial and access subgroup. *Event rates expressed as number of events per 100 patient-years. Risk of Vascular Access Complications with Frequent HD Suri RS et al J Am Soc Nephrol. 24:498-505,2013 3 TIMES PER WEEK6 TIMES PER WEEK 6 times/wK better 3 times/wK better Daily Trial Nocturnal Trial All patients AV access Catheter

12. Effect of frequent HD on residual kidney function Daugirdas JT et al Kidney Int. 2013; 83:949-58. % of patients Baseline Month 4 Month 12 Convent Frequent nocturnal Convent Frequent nocturnal Convent Frequent nocturnal Urine vol (ml/day) subjects with baseline non-zero urine volume This post hoc analysis of FNH Trials suggests that frequent nocturnal HD, may be associated with more rapid loss of RRF than conventional HD. The study invites reflection on the indications for frequent nocturnal HD. EDITORIAL K. Farrington Kidney International 2013 83, 787–789.

13. Comparison of dose measures for differing schedules and renal function Tattersall J, Martin-Malo A, Pedrini L, Basci A, Canaud B, Fouque D, Haage P, Konner K, Kooman J, Pizzarelli F, Tordoir J, Wanner C, ter Wee P, Vanholder R. Nephrol Dial Transplant. 2007

14. In-center Frequent HD 2.1 We suggest that patients with end-stage kidney disease be offered in-center short frequent hemodialysis as an alternative to conventional in-center thrice weekly hemodialysis after considering individual patient preferences, the potential quality of life and physiological benefits, and the risks of these therapies. (2C) 2.2 We recommend that patients considering incenter short frequent hemodialysis be informed about the risks of this therapy, including a possible increase in vascular access procedures (1B) and the potential for hypotension during dialysis. (1C) Home Long HD 2.3 Consider home long hemodialysis (6-8 hours, 3 to 6 nights per week) for patients with end-stage kidney disease who prefer this therapy for lifestyle considerations. (Not Graded) 2.4 We recommend that patients considering home long frequent hemodialysis be informed about the risks of this therapy, including possible increase in vascular access complications, potential for increased caregiver burden, and possible accelerated decline in residual kidney function. (1C) Guideline 2: Frequent and Long Duration Hemodialysis

15. Demographic characteristics Comorbidity Age Gender Race Diabetes (30%) CV disease (76%) Nutritional status Vascular Access Dialysate purity Treatment complic ALTERNATIVES TO CONVENTIONAL HD High-flux membranes Longer dialysis Short daily HD Long Nocturnal HD Hemodiafiltration On-line HDF

16. CONTRAST study Grooteman MP et al J Am Soc Nephrol. 2012 23:1087-1096

17. Mortality and cardiovascular events in OL-HDF compared with high-flux HD: Turkish OL-HDF Study Overall Survival Cardiovascular Survival Months OL_HDF>17.4 L OL-HDF<17.4 L High-flux HD OL_HDF>17.4 L OL-HDF<17.4 L High-flux HD P=0.03P=0.002 Ok E et al Nephrol Dial Transplant. 2013; 28:192-202

18. Follow-up (months) Survival Probability OL-HDF HD Log-rank p value:0.010 High-Efficiency Postdilution OL-HDF Reduces All-Cause Mortality ESHOL study Maduell F et al J Am Soc Nephrol 2013, 24:487-97 CV>22.0L Hemodiafiltration Versus Hemodialysis and Survival in Patients With ESRD: The French Renal Epidemiology and Information Network (REIN) Registry Mercadal L et al Am J Kidney Dis. 2015 Dec 24. [Epub ahead of print]

19. Sirich T L et al J Am Soc Nephrol 2014;25:615-622 Accumulation in HD Patients of Solutes Normally Cleared by Tubular Secretion Pérdida de albúmina Adsorción

20. Prospective crossover study  n = 17 patients Blood samples at the end of each period HFRS-1 OLHDF-1 OLHDF2HFRS-2 8-week periods HF-HD Ultrafiltrate samples in HFRS 1 y 2 E Esquivias et al Artificial Organs 2016

21. Variable Baseline a (n=17) HFR1 (n=15) OLHDF1 (n=14) HFR2 (n=12) OLHDF2 (n=9) Serum p-cresyl sulfate reduction ratio (%) b 39.0 [21.7–44.2]52.0 [43.0–66.0] ce 35.4 [27.4–58.7]44.2 [29.4–65.6]41.7 [37–52.8] Serum indoxyl sulfate reduction ratio (%) b 45.4 [40–59.7]57.3 [47.5–79.7] ce 46.2 [42.6–55.4]52.2 [42.9–56.8]60.0 [39.2–62.7] Plasma IL-6 (pg/mL) 44.3 [32.9–55.7]20.2 [16.5–32.6] ce 37.9 [22.1–43.2] c 18.5 [7.7–23.9] ce 27.7 [19.6–30.9] c Plasma TNF- α (pg/mL) 50.4 [35.7–58.0]23.4 [14.3–31.3] ce 34.2 [24.1–44.5] c 24.8 [14.5–36.2] ce 28.7 [22.6–30.8] c CD14+CD16+ monocytes (%) 14.0 [10.1–21.3]7.0 [5.6–12.3] cef 12.3 [10.0–17.3]6.6 [4.3–9.3] cef 13.5 [9.1–15.4] c CD14++CD16+ monocytes (%) 6.2 [3.1–9.6]2.5 [2.0–3.0] cef 4.2 [3.8–7.1] c 2.3 [1.8–2.9] cef 3.2 [2.5–4.8] EPC (/100000 peripheral blood cells) 5000 [4000–9000]12000 [10000–18000] cef 7 000 [6 000–10 000] c 12000 [10000–14000] cef 9000 [5000–12000] Plasma EMP (/µL) 116.0 [67.5–139.0]70.0 [37.0–123.0] ce 120.5 [55.2–136.7] f 75.5 [54.7–107.5] ce 76.0 [40.5–114.0] c Plasma VEGF (pg/mL) 233.2 [178.2–310.5]153.2 [102.5–222.5] cef 172.9 [122.2–368.0] c 126.7 [99.2–227.6] cef 271.7 [167.5–332.8] Plasma VCAM (ng/mL) 4022.7 [3272.7–4875.0]2204.5 [2068.2–2522.7] ce 3 196.4 [2 866.6–4 701.0] cf 2019.9 [1676.0–2326.6] cf 2822.3 [2143.6–3054.1] c Plasma Ang2 (pg/mL) 1752.5[1499.0–2030.6]1380.2 [1081.5–1698.7] c 1933.4 [1477.2–2076.5] c 1602.6 [1046.0–1859.6]1789.0 [1546.8–1987.7] Plasma Ang1 (pg/mL) 526.0 [455.3–737.2]684.7 [574.7–927.3] cde 537.7 [505.4–605.2] f 727.7 [704.7–836.4] cef 627.7 [551.8–732.3] c Plasma Ang2/Ang1 ratio 3.0 [2.6–3.5]1.9 [1.6–2.9] ce 3.5 [2.2–3.8]1.9 [1.4–2.5] ce 2.8 [2.1–3.3] cd Plasma annexin V (ng/mL) 16.9 [12.7–20.5]7.9 [7.2–13.1] cef 14.4 [12.0–17.1] cf 8.4 [7.4–11.9] cef 13.3 [10.9–14.3] c Plasma SOD (ng/mL) 186.6 [141.1–219.8]385.23 [328.5–417.7] cef 292.7 [265.3–329.5] c 388.7 [355.3–405.5] cef 321.1 [287.4–353.4] c

22. VARIABLE Baseline a HFROLHDF Serum p-cresyl sulfate reduction ratio (%) b 42.2 [22.7–47.8]50.7 [34.1-68.1] e 44.8 [32.9-55.8] Serum indoxyl sulfate reduction ratio (%) b 41.9 [38.2–59.6]53.7 [48.8-67.3] f 45.2 [38.3-56.3] Hemodiafiltration With Endogenous Reinfusion Improved Micro- inflammation and Endothelial Damage Compared With Online-HDF: A Hypothesis Generating Study DIALYSIS TECHNIQUE

24. Medscape Medical News from the: American Society of Nephrology 35th Annual Dialysis Conference New Wearable Artificial Kidney Improves Mobility

25. “An ounce of prevention is worth a pound of cure” Benjamin Franklin

27. 4D-STUDY Krane et al, Am J Kidney Dis, 49, 267-275, 2007 Dialyzer Membrane Characteristics and Outcome of Patients With Type 2 Diabetes on Maintenance Hemodialysis 1.00 0.95 0.90 0.85 0.80 0.75 0.70 0.65 0.60 0.55 0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00 Proportion of patients surviving 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 Year HF synthetic LF synthetic LF semisynthetic LF cellulosic Dialyser CONCLUSION: These data suggest that biocompatibility and permeability may impact on death and cardiovascular events in HD patients with type 2 diabetes mellitus.