HDx THERAPY. Enabled by. Making possible personal.

Size: px

Start display at page:

Download "HDx THERAPY. Enabled by. Making possible personal."

Arnold Michael Thompson
5 years ago
Views:

1 HDx THERAPY Enabled by Making possible personal.

THE NEXT HORIZON IN DIALYSIS IS CLOSER THAN YOU THINK PHOSPHATE UREA HDx BY THERANOVA EXPANDS YOUR RENAL POSSIBILITIES The new HDx therapy (expanded HD) is the next evolution in hemodialysis, as it

2 THE NEXT HORIZON IN DIALYSIS IS CLOSER THAN YOU THINK PHOSPHATE UREA HDx BY THERANOVA EXPANDS YOUR RENAL POSSIBILITIES The new HDx therapy (expanded HD) is the next evolution in hemodialysis, as it effectively targets the removal of large middle molecules. 1 Indeed, many of them are linked to the development of inflammation, cardiovascular disease, and other co-morbidities in dialysis patients. 2 Not only can HDx therapy provide HDF performance and beyond in the removal of conventional middle and large middle molecules, it does so using regular HD workflow and infrastructure. 3 The HDx therapy is enabled by the THERANOVA dialyzer featuring an innovative membrane that combines a higher permeability than regular high-flux dialyzers with effective selectivity for large proteins. 4,5 This new therapy opens up a new option for dialysis patients who are believed to benefit from effective removal of large uremic toxins, for clinics that want expanded dialysis performance without the added burden of HDF. INTERLEUKIN-6 BETA 2 MICROGLOBULIN COMPLEMENT FACTOR D LAMBDA FREE LIGHT CHAINS CREATININE Do not use THERANOVA dialyzers in HDF or HF mode

3 CHANGE ONE THING CHANGE EVERYTHING EXPLORE THE HDx THERAPY BY THERANOVA Mortality from cardiovascular and infectious events in HD remains unsatisfactorily high with current dialytic therapies. 6 Large middle molecules have been associated with inflammation, cardiovascular events and other dialysis-related comorbidities. 2 Current dialytic therapies, though efficient in removing small solutes, have limited capability in removing large middle molecules. 7 CATEGORIZATION OF UREMIC SOLUTES Non-protein bound uremic solutes accumulating in chronic kidney disease can be divided into three main categories. 5 Small molecules < 5 Da Effective removal by diffusion Conventional middle molecules 5-15, Da Limited removal by diffusion, compensated by applying convection Large middle molecules 15, - 6, Da Require higher permeability membranes for effective removal HD HDF UREA (6 Da) PHOSPHATE (96 Da) CREATININE (113 Da) PTH (9,5 Da) BETA 2 MICROGLOBULIN (11,8 Da) HDx enabled by CYSTATIN C (13,3 Da) HDx is a new therapy targetting an efficient removal of large middle molecules, without the need for a more complex setup than in regular HD. The HDx therapy is delivered with an innovative dialyzer featuring a new type of membrane, combining a higher permeability than high-flux dialyzers with effective selectivity to retain essential proteins. 4,5 COMPLEMENT FACTOR D (24, Da) HDx ALPHA-1 MICROGLOBULIN (33, Da) LAMBDA FREE-LIGHT-CHAINS (45, Da)

SHIFTING FOCUS TO LARGE MIDDLE MOLECULES EXAMINING UREMIC TOXINS BEYOND BETA 2 MICROGLOBULIN There is growing evidence showing a link between large middle molecules and the development of different

4 SHIFTING FOCUS TO LARGE MIDDLE MOLECULES EXAMINING UREMIC TOXINS BEYOND BETA 2 MICROGLOBULIN There is growing evidence showing a link between large middle molecules and the development of different outcome-related morbidities: Complement factor D (24 kda) α1- (33 kda) YKL-4 (4 kda) Immunoglobulin Free Light Chains (22.5 and 45 kda) More than the specific impact that each and every large middle molecule may have on the health of chronic kidney disease patients, it is critical to understand and address their collective effect. Uremia related to the retention of large middle molecules is indeed associated with inflammation and cardiovascular events. 8,9,1 LARGE MIDDLE MOLECULES ARE ASSOCIATED WITH INFLAMMATION AND CARDIOVASCULAR EVENTS CO-MORBIDITIES RETENTION OF UREMIC SOLUTES INFECTIOUS COMPLICATIONS INFLAMMATION OXIDATIVE STRESS REDUCED APPETITE INCREASED CATABOLISM ENDOTHELIAL DYSFUNCTION VASCULAR CALCIFICATION PROTEIN-ENERGY WASTING PROGRESSION OF CARDIOVASCULAR DISEASES

A STEP CLOSER TO THE NATURAL KIDNEY TURNING INNOVATIVE DESIGN INTO A CLINICAL SOLUTION The THERANOVA dialyzer enables the HDx therapy by combining 4 therapeutic principles: permeability, selectivity,

Its innovative medium cut-off (MCO) membrane expands the range of solutes removed during regular dialysis, while retaining essential proteins at a safe and controlled level.

4,5 THE MEMBRANE STRUCTURE IS ASYMMETRIC AND CAN BE SEEN IN CROSS SECTION AS THREE DISTINCT LAYERS: A finger-like macro-porous

5 A STEP CLOSER TO THE NATURAL KIDNEY TURNING INNOVATIVE DESIGN INTO A CLINICAL SOLUTION The THERANOVA dialyzer enables the HDx therapy by combining 4 therapeutic principles: permeability, selectivity, retention and internal filtration into a single dialyzer design. Its innovative medium cut-off (MCO) membrane expands the range of solutes removed during regular dialysis, while retaining essential proteins at a safe and controlled level. This unique cut-off and retention onset profile allows for filtration close to that of the natural kidney.4,5 THE MEMBRANE STRUCTURE IS ASYMMETRIC AND CAN BE SEEN IN CROSS SECTION AS THREE DISTINCT LAYERS: A finger-like macro-porous outer layer A sponge-like intermediate layer Number of pores [a.u.] High ﬂux THERANOVA High cut-off A very thin inner layer (skin) Pore radius [nm] HIGHER PERMEABILITY With an increased nominal pore size, the THERANOVA dialyzer has a significantly higher permeability for large middle molecules compared to regular high-flux membranes, before and after blood contact. RETENTION EFFECTIVE SELECTIVITY FOR LARGE PROTEINS By combining a unique asymmetric 3-layer structure with a carefully controlled distribution of the pore size, the THERANOVA dialyzer enables a stable separation profile and selectivity throughout the treatment, keeping albumin removal at a controlled level. The adsorption properties of the THERANOVA membrane maintain the same level of bacteria and endotoxin retention as other standard dialysis membranes.11 Despite its higher permeability, the THERANOVA membrane appears to be a safe and effective barrier to potential dialysis fluid contaminants. It is compatible with standard fluid quality (ISO 11663:214) and does not require any additional fluid quality control measure.12 INTERNAL FILTRATION 1. The inner diameter of the THERANOVA membrane has been carefully reduced in order to increase internal filtration along the membrane, conducive to an enhanced removal of large middle molecules. Sieving coefﬁcient Sieving coefﬁcient Low-ﬂux Low-ﬂux High-ﬂux High-ﬂux THERANOVA THERANOVA Glomerular membrane Glomerular membrane 1 4 Smaller inner diameter and reduced wall thickness Greater packing density Dextran molecular weight [g/mol] Dextran molecular weight [g/mol] MEMBRANE GEOMETRY A STEP CLOSER TO THE NATURAL KIDNEY By expanding the range of solutes removed in dialysis, while retaining selectivity towards albumin and other essential proteins, the THERANOVA dialyzer is coming a step closer to the natural kidney. Improved undulation HIGH-FLUX THERANOVA 3-5 μm μm 35 μm 18 μm

EXPANDED HEMODIALYSIS (HDx) TREATMENT EFFECTS AND THERAPY IMPLICATIONS (VS. HD) 3 HD therapies have been the treatment of choice for many years both for many patients and many clinics.

6 EXPANDED HEMODIALYSIS (HDx) TREATMENT EFFECTS AND THERAPY IMPLICATIONS (VS. HD) 3 HD therapies have been the treatment of choice for many years both for many patients and many clinics. The design and operating mode of the THERANOVA dialyzer enables the HDx therapy to be easily implemented on any HD monitor. 13 This means by simply changing the dialyzer, any clinic can provide markedly greater clearances and intradialytic reduction ratios than regular HD at ordinary blood flow rates. ml/min 1 HDx HDx THERANOVA THERANOVA 4 4 HD FX CORDIAX 8 HD FX CORDIAX 8 p <.1 vs high-fl ux HD p <.1 vs high-fl ux HD beta 2 11,818 Da myoglobin 17, Da kappa free 22,5 Da complement factor D 24, Da alpha 1 33, Da lambda free 45, Da OVERALL CLEARANCE HDx VS. HD HDx with Theranova 4 dialyzer HD with latest generation high-flux dialyzer Qb = 3 ml/min Treatment Time = 4 h (Mean) n = 19 1 % HDx HDx THERANOVA THERANOVA 4 4 HD FX CORDIAX 8 HD FX CORDIAX 8 p <.1 vs high-fl ux HD p <.1 vs high-fl ux HD beta 2 11,818 Da myoglobin 17, Da kappa free 22,5 Da complement factor D 24, Da alpha 1 33, Da YKL-4 4, Da lambda free 45, Da REDUCTION RATIO HDx VS. HD HDx with Theranova 4 dialyzer HD with latest generation high-flux dialyzer Qb = 3 ml/min Treatment Time = 4 h (Mean) n = 19

7 EXPANDED HEMODIALYSIS (HDx) TREATMENT EFFECTS AND THERAPY IMPLICATIONS (VS. HDF) 3 HDx therapy enabled by the THERANOVA dialyzer provides an equivalent removal of small and conventional middle molecules, with the possibility of greater removal for large middle molecules when compared to high-volume HDF. HDx performance can be achieved in all regular HD environments: this simplicity removes the potential burden of patient eligibility or therapy specific delivery systems. ALBUMIN REMOVAL PER SESSION: REMOVAL DURING CLINICAL TRIAL SESSIONS (IN GRAMS) Qb = 3 ml/min Qb = 4 ml/min T = 4 h T = 4.4 h Mean (± SD) 2.7±.7 3.±.7 Median Range ml/min 1 8 HDx HDx with with THERANOVA THERANOVA 4 4 HDF post FX CORDIAX 8 HDF post FX CORDIAX 8 p <.1 vs HDF p <.1 vs HDF p <.1 vs HDF p <.1 vs HDF 3 grams on average in all cases, limited to between 1 and 4 grams per treatment. Similar removal compared to HDF on-line. Does not seem to have any impact on serum albumin levels after 6 months compared to HDF beta 2 11,818 Da myoglobin 17, Da kappa free 22,5 Da complement factor D 24, Da alpha 1 33, Da lambda free 45, Da OVERALL CLEARANCE HDx VS. HDF HDx with Theranova 4 dialyzer HDF with latest generation high-flux dialyzer for HDF Qb = 4 ml/min Treatment Time = 4.4 h Vconv = 24L (Mean) n = 2 % 1 HDx HDx with with THERANOVA THERANOVA 4 4 HDF post FX CORDIAX 8 HDF post FX CORDIAX 8 p <.1 vs HDF p <.1 vs HDF p <.1 vs HDF p p <.5.1 vs. HDF p <.5 vs. HDF beta 2 11,818 Da myoglobin 17, Da kappa free 22,5 Da complement factor D 24, Da alpha 1 33, Da YKL-4 4, Da lambda free 45, Da REDUCTION RATIO HDx VS. HDF HDx with Theranova 4 dialyzer HDF with latest generation high-flux dialyzer for HDF Qb = 4 ml/min Treatment Time = 4.4 h Vconv = 24L (Mean) n = 2

HDF PERFORMANCE AND BEYOND Equivalent removal of small and conventional middle molecules. Greater removal possible for large middle molecules. Applicable to all HD patients.

8 HDF PERFORMANCE AND BEYOND Equivalent removal of small and conventional middle molecules. Greater removal possible for large middle molecules. Applicable to all HD patients. AS SIMPLE AS HD HD infrastructure: no need for HDF capable monitors nor specific water quality and fluid quality assurance measures. 15 Avoid HDF additional running costs: disposable infusion line, use of larger amounts of dialysis water and concentrates. 16 Avoid requirement for specialist training and extensive monitoring during therapy delivery. 17 Do not use THERANOVA dialyzers in HDF or HF mode

REFERENCES 1. Ronco C, et al. The rise of Expanded Hemodialysis. Blood Purif 217; 44:I VIII 2. Hutchison CA, et al. The Rationale for Expanded Hemodialysis Therapy (HDx).

9 REFERENCES 1. Ronco C, et al. The rise of Expanded Hemodialysis. Blood Purif 217; 44:I VIII 2. Hutchison CA, et al. The Rationale for Expanded Hemodialysis Therapy (HDx). Contrib Nephrol 217; 191: Kirsch AH, et al. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol Dial Transpl 217; 32(1): Boschetti-de-Fierro A, et al. MCO membranes: Enhanced Selectivity in High-Flux Class. Scientific Reports 215; 5: Zweigart C, et al. Medium cut-off membranes closer to the natural kidney removal function. Int J Artif Organs 217; 4(7): Himmelfarb J, Ikizler TA. Hemodialysis. N Engl J Med 21; 363(19): Chmielewski M, et al. The Peptidic Middle Molecules: Is Molecular Weight Doing the Trick? Sem in Nephro 214; vol. 34, March, Yilmaz MI, et al. Low-grade inflammation in chronic kidney disease patients before the start of renal replacement therapy: sources and consequences. Clinical Nephro 212; vol. 68, July, pp Stenvinkel P, et al. Can treating persistent inflammation limit protein energy wasting? Sem in Dialysis 212; vol. 26, January-February, pp Akchurin OM, et al. Update on inflammation in chronic kidney disease. Blood Purif 215; vol. 39, May, pp Schepers E, et al. Assessment of the association between increasing membrane pore size and endotoxin permeability using a novel experimental dialysis simulation set-up. BMC Nephrology 218; 19:1 12. Baxter. Theranova 4/5 Instructions For Use. N5 648 rev 3, Baxter. Data on file. Theranova Limited Controlled Distribution Report Belmouaz M, et al. Comparison of hemodialysis with medium cut-off dialyzer and on-line hemodiafiltration on the removal of small and middle size moelcules. Clinical Nephro 218; 89 (1): Mazairac A, et al. The cost-utility of hemodiafiltration versus hemodialysis in the Convective Transport Study. Nephrol Dial Transplant; 28: Baxter. Data on file. Therapy Cost Calculator Chapdelaine I, et al. Optimization of the convection volume in online post-dilution hemodiafiltration: practical and technical issues. Clin Kidney J 215; 8: These products meet the applicable provisions of Annex I (Essential Requirements) and Annex II (Full quality assurance system of the Council Directive 93/42/EEC of 14 June 1993, amended by Directive 27/47/EC) For further information visit hdxtheranova.com: Baxter Healthcare Corporation One Baxter Parkway Deerfield, IL 615 USA MANUFACTURER Gambro Dialysatoren GmbH Holger-Crafoord-Strasse Hechingen Germany Baxter, Gambro, Making possible personal, MCO and Theranova are trademarks of Baxter International Inc. or its subsidiaries. Cordiax is a trademark of Fresenius Medical Care Deutschland GmbH. GLBL/MG29/17-2 February 218

Making possible personal.

Making possible personal. HDX THERAPY, ENABLED BY THE THERANOVA DIALYZER HDF PERFORMANCE AND BEYOND AS SIMPLE AS HD The THERANOVA dialyzer, featuring an innovative membrane, effectively targets large middle