HEMODIAFILTRATION PRINCIPLES AND ADVANTAGES OVER CONVENTIONAL HD PRESENTATION BY DR.ALI TAYEBI

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1 HEMODIAFILTRATION PRINCIPLES AND ADVANTAGES OVER CONVENTIONAL HD PRESENTATION BY DR.ALI TAYEBI

2 high-flux Hemodiafiltration (HDF) Combination of two dialysis techniques, hemodialysis and hemofiltration: high clearance of conventional small molecules by diffusion linked with high clearance of middle molecules by convection mmhg F B mmhg Diffusion + Convection + Adsorpti D S 2

3 low-flux Hemodialysis (HD) PV D SAD D PA Heparin PBE BLD D UF Diffusion Blood Pump B Water soluble molekuls 3

4 high-flux Hemofiltration (HF) S S mmhg PV Postdilution Sub. Pump F SAD BLD UF Convection Heparin PBE Adsorption PA mmhg B H 2 O water soluble molekuls Blood Pump 4

5 high-flux Hemodiafiltration (HDF) Postdilution Sub. Pump S S PV D D SAD PA Heparin PBE BLD D UF Diffusion/Conve mmhg Adsorption F Blood Pump mmhg B H 2 O water soluble molekuls 5

6 Clearance in HD, HF and HDF Clearance ml/min 120 Cut-off HD HF HDF Kidney 0 MG Dalton Urea Creatinine Vit. B 12 ß 2 -Microglob. Albumine 6

7 Predilution high-flux HDF with Bag Scale S Postdilution Sub. Pump PV SAD D PA Heparin PBE BLD D UF Blood Pump 7

8 Predilution high-flux HDF with Bag HDF on-line Scale S On-line Port Postdilution Sub. Pump PV SAD D PA Heparin PBE BLD D UF Blood Pump 8

9 HDF - Clinical Parameters In postdilution ratio blood/total UF should be 25-30% In postdilution total substitution volume up to 1/3 of patient s body weight In predilution up to 100% of body weight Required blood flow ml/min Example for postdilution: body weight 81 kg weight loss 2 kg treatment time 4 h blood flow 300 ml/min total UF rate75 ml/min (4.5 l/h) total UF in 4h 18 l net UF 2 l sub. volume 16 l blood flow 400 ml/min total UF rate100 ml/min (6 l/h) total UF in 4h 24 l net UF 2 l sub. volume 22 l 9

10 Advantages of HDF 1.Clearance of uraemic solutes across a wide molecular weight range 2.Biocompatibility 3.Hemodynamic stability ß 2 -microglobulin amyloidosis in large cohort studies show that use of high-flux membranes and convective therapies reduce the incidence of carpal tunnel syndrome, CTS. Probably due to use of ultrapure water biocompatible material (less inflammation) ß 2 -microglobulin removal (Shiffl, 2014) better anemia correction and less erythropoiesis stimulating agent (ESA) consuption (Susantitaphong, 2013) lower inflammatory profile with less activation of c-reactive protein interleukins in prospective studies (Susantitaphong, 2013) less hypotensive episodes probably due to cool substitution fluid higher sodium in substitution fluid removal of vasodilating mediators (Van der Sande, 2001) Reduction of hypotensive events results in better cardio protective effect (Ohtake, 2012)

11 1. Clearance on HDF vs HD

12 β2microglmicroglobulin clearance HDF achieves 70 78% reduction in β2 microglobulin (vs 40 50% with highflux HD) Thomas et al, Semin Dialy, 2009 No signs of amyloidosis after 8 yrs on HDF (vs 100% pts on HD have amyloid by 13 yrs) Canaud et al, NDT, % reduced incidence of carpal tunnel syndrome and 67% reduced incidence of erosive arthritis Dember et al, Semin Dialy, 2006 For every 10 mg /l increase in predialysis ß2M there is a 11% increase risk of death (HEMO Study) Cheung et al, JASN 2000

13 β2microgl-microglobulin in our HD vs HDF patients p = 0.02microgl Significant association with convective volume (>15L/m2 β2-microglmicroglobulin < 25mg/L) No further reduction with increasing time on

14 Other middle molecules cleared by HDF Parathyroid hormone Inflammatory cytokines (IL-6, IL-8, IL-12) Homocysteine Guanidine Polyamines INFLUENCE ENDOTHELIAL FUNCTION: -REDUCE NITRIC OXIDE PRODUCTION -PROMOTE AGE FORMATION -AFFECT CELL CYCLE AND CAUSE SENESCENCE Appetite suppressants (leptin, cholecystokinin, tryptophan)

15 2microgl. Reduced inflammation and oxidative stress 1.reduces inflammation ( TNF, IL-6, IL-8, IL-12) 2.suppresses oxidative stress ( reactive oxygen species and superoxide) 3.improves antioxidant capacity 4.reduces generate on of AGEs Mechanisms: 1.Biocompatible membranes 2. Ultrapure dialysate 3.Removal of cytokines

16 Chronic low-grade exposure to endotoxins Chronic inflammation Anorexia, poor nutrition and growth, catabolism, loss of lean body mass cachexia Anaemia poor ESA response Risk of atherosclerosis MALNUTRITION INFLAMMATION ATHEROSCLEROSIS COMPLEX

17 IMPROVED ANAEMIA CONTROL ON HDF

18 3. Hemodynamic stability 1.Fewer intra-dialytic hypotensive episodes 2.Higher UF better tolerated by patient 3.Reduced post-dialysis fatigue 4.Overall better BP control Mechanisms: 1.Cooling of dialysate 2.Removal of vasodilating mediators 3.High Na content of infusion fluid

19 Cardiovascular and survival advantage of HDF vs HD

20 1. Dutch HDF Study: CONTRAST

21 2microgl. Turkish HDF Study: High vs Low Efficiency HDF

22 Nutrition & growth in children on dialysis Growth failure is a common end point of multiple CKD-related abnormalities : Malnutrition anorexia and reduced energy intake Cachexia - protein energy wasting - due to chronic inflammation and inadequate dialysis % of children with ESRD grow up to become short adults (final height <3rd centile)

23 Growth study in children 15 children on daily HDF; mean age: 7.3 ( yrs) 7 converted from PD & 5 from 3/week HD Vascular access: fistula (n=13) & catheter (n=4) Pre-dilution HDF; Qb & Qd adjusted to achieve a Kt/Vurea 1.4 per session x 18 hours per week

Growth on daily HDF NOTE: - High convective volume - Daily HDF Height SDS - start: -1.5 ± 0.3 - end: +0.2 ± 1.

24 Growth on daily HDF NOTE: - High convective volume - Daily HDF Height SDS - start: -1.5 ± end: +0.2 ± target height relative to mid-parental height: +0.3 al; NDT, 2010 Growth on daily HDF Height velocity - before daily HDF: 3.8 ±1.1 cm/y - first year of daily HDF: 14.3 ± 3.8 cm/ - mean : 10.4 cm/y

25 Diet and medications Start of daily HDF (n= 12) After 1 year on daily HDF (n=12)

26 Dialysis efficiency & tolerance Mean weekly Kt/Vurea =10 - dialysis dose ~ 35% GFR Phosphate: 1.39 ( ) mmol/l - despite high protein intake (>2 g/kg/day) - 2/15 child on chelators CRP normal in 13/15 (2 children had chronic infections) β2 microglobulin 13.5 ± 3.5 mg/l

27 Anabolic effect of daily HDF Stimulates appetite - removal of circulating satiety factors (leptin, cholecystokinin, tryptophan) Correction of metabolic acidosis. Acidosis can: - activate the ubiquitin-proteosome pathway & increase protein degradation - suppresses endogenous GH secretion Minimises inflammatory cytokine release Removal of somatomedin and gonadotropin inhibitors by HDF reverses rhgh resistance

28 The effects of HDF vs conventional HD on growth and cardiovascular markers in children n 3H (HDF, Hearts and Height) study Hypothesis Children on HDF compared with HD have improved: Cardiovascular risk profile Growth and nutritional status Quality of life

29 Summary HDF offers many advantages over HD - improved clearance of uraemic toxins - biocompatibility - hemodynamic stability HDF is not widely practiced in children Ongoing study to examine effects of HDF on growth and cardiovascular outcomes

30 Thank you! Any question

Hemodiafiltration: principles and advantages over conventional HD. Rukshana Shroff Great Ormond Street Hospital for Children London, UK

Hemodiafiltration: principles and advantages over conventional HD Rukshana Shroff Great Ormond Street Hospital for Children London, UK Effectiveness of RRT modalities Mcfarlane, Seminars in dialysis, 2009