Making possible personal.

Size: px

Start display at page:

Download "Making possible personal."

Gwendolyn Holland
6 years ago
Views:

1 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 molecules not

2 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 molecules not efficiently removed by currently available dialysis treatments. It provides the opportunity for an expanded hemodialysis therapy, HDx, providing HDF performance and beyond in the removal of middle and larger middle molecules, using regular HD infrastructure. The premium performance and simplicity of the HDx therapy, enabled by the THERANOVA dialyzer, opens up another option for patients with chronic or acute renal failure requiring hemodialysis. Do not use THERANOVA dialyzers for HDF or HF due to higher permeability of larger molecular weight proteins such as albumin.

FOCUS ON LARGE MIDDLE MOLECULES CONVENTIONAL DIALYSIS THERAPIES FAIL TO ADDRESS ALL UREMIC SOLUTES SHIFTING FOCUS TO LARGER MIDDLE MOLECULES AND GREATER MEMBRANE PERMEABILITY There is an unmet need

These are larger middle molecules and are not removed effectively by current dialytic modalities unless the dialyzer membrane pore size is large enough.

1 Then came in focus as high-flux dialysis was more commonly applied, largely due to its role in dialysis-related amyloidosis.

3 FOCUS ON LARGE MIDDLE MOLECULES CONVENTIONAL DIALYSIS THERAPIES FAIL TO ADDRESS ALL UREMIC SOLUTES SHIFTING FOCUS TO LARGER MIDDLE MOLECULES AND GREATER MEMBRANE PERMEABILITY There is an unmet need in helping patients long-term health.3 Progressive loss of renal function leads to the accumulation in body fluids of several compounds that are in the size range of 15 to 55 kda. These are larger middle molecules and are not removed effectively by current dialytic modalities unless the dialyzer membrane pore size is large enough.4 Dialysis adequacy was early on defined as the degree of urea reduction, and urea Kt/V still plays a role as dose marker.1 Then came in focus as high-flux dialysis was more commonly applied, largely due to its role in dialysis-related amyloidosis.2 Today, large middle molecules, larger in size than, are increasingly seen as important to consider when prescribing dialysis.4 Dialytic removal of such large middle molecules is called for.5 F ree immunoglobulin (FLCs, 22.5 and 45 kda): plasma levels of kappa and lambda FLCs progressively increase as renal function deteriorates7 Complement (24 kda): circulating rate-limiting enzyme in the alternative system8 that in advanced kidney disease shows approximately a 1-fold increase in plasma9 Alpha 1 (33 kda): commonly used marker for the removal by dialysis of large middle molecules1 Y KL-4 (4 kda): plasma level is approximately doubled in dialysis patients compared to healthy people and shows a positive correlation with the C-reactive protein level in plasma11 urrent dialyzer design, limited by membrane permeability, does C not provide long-lasting, effective reduction of middle molecules, even when their usage is enhanced with convective transport.12 There is an unmet need to lower these toxic substances, and therefore strategies for their effective removal should be developed.13 CATEGORIZATION OF UREMIC SOLUTES Non-protein bound uremic solutes accumulating in chronic kidney disease can be divided into three main categories. Small molecules < 5 Da Effective removal by diffusion Classification Molecular Weight Of Solutes Range (Daltons)6 urea (6) phosphate (96) Conventional Middle molecules 5-15 Da Limited removal by diffusion, compensated by applying convection creatinine (113) (11818) Large Middle molecules > 15 Da Require higher permeability membranes for effective removal (17) (225) (24) (33) YKL-4 (4) (45)

ACHIEVED THROUGH MEMBRANE INNOVATION DESIGNED TO TARGET MIDDLE MOLECULES EFFECTIVELY AND SAFELY WITH SAFETY IN MIND THE MEMBRANE CROSS-SECTIONAL STRUCTURE IS ASYMMETRIC AND CHARACTERIZED BY THREE

PERMEABILITY With an increased nominal pore size along the membrane, the THERANOVA dialyzer has a significantly higher permeability for large middle molecules than conventional high-flux membranes.

4 ACHIEVED THROUGH MEMBRANE INNOVATION DESIGNED TO TARGET MIDDLE MOLECULES EFFECTIVELY AND SAFELY WITH SAFETY IN MIND THE MEMBRANE CROSS-SECTIONAL STRUCTURE IS ASYMMETRIC AND CHARACTERIZED BY THREE DISTINCT LAYERS: Number of pores [a.u.] a very thin inner layer (skin) a sponge-like intermediate layer a finger-like macroporous outer layer High flux THERANOVA membrane High cut-off Pore radius [nm] 2, 4, 6, 8, 1, 12, 14, HIGHER PERMEABILITY With an increased nominal pore size along the membrane, the THERANOVA dialyzer has a significantly higher permeability for large middle molecules than conventional high-flux membranes. 14,15 ENHANCED SELECTIVITY BY SIZE EXCLUSION The THERANOVA dialyzer membrane, combining a unique asymmetric 3-layer structure 16,18 with an increased nominal pore size along the membrane s inner layer, enables a stable separation profile and selectivity throughout the treatment. 1,,8,6 Sieving coefficient Low-flux High-flux THERANOVA membrane High cut-off Glomerular membrane,4, Dextran molecular weight [g/mol] The smooth blood-contacting surface of the skin layer, characterized by hydrophobic/ hydrophilic micro-domains, minimizes interaction with blood components, resulting in lower protein adsorption and cell interaction, which may help reduce risk of clotting. 19 WELL-PROVEN TECHNOLOGY WITH NO-ADDED COST A STEP CLOSER TO THE NATURAL KIDNEY By expanding the range of solutes removed in dialysis, while retaining selectivity towards albumin and other essential The DIASCAN proteins, the monitoring THERANOVA system dialyzer is is coming based a on step reliable closer to conductivity the natural kidney. measurements 14,15 of the dialysis fluid, it is accurate and does not require additional disposables. Fluid path integration on the AK 98 system makes it a fully automated function fitting easily within your clinical workflow.

5 TREATMENT EFFECTS AND THERAPY IMPLICATIONS OVERALL CLEARANCE HDx VS. HD 2 HDx with THERANOVA 4 dialyzer HD with latest generation high-flux dialyzer Qb = 3 ml/min Treatment Time = 4 h (Mean) n = 19 OVERALL CLEARANCE HDx VS. HDF 2 p <.1 vs high-flux HD HDx with THERANOVA 4 dialyzer HDF with latest generation high-flux dialyzer for HDF * p <.1 vs HDF Qb = 4 ml/min Treatment Time = 4.4 h Vconv = 24L (Mean) n = 2 p <.1 vs HDF ml/min HDx THERANOVA 4 HD FX CORDIAX 8 ml/min * HDx with THERANOVA 4 HDF post FX CORDIAX Da 225 Da 24 Da 33 Da 45 Da Da 225 Da 24 Da 33 Da 45 Da REDUCTION RATIO HDx VS. HD 2 HDx with THERANOVA 4 dialyzer HD with latest generation high-flux dialyzer Qb = 3 ml/min Treatment Time = 4 h (Mean) n = 19 p <.1 vs high-flux HD REDUCTION RATIO HDx VS. HDF 2 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 * p <.1 vs HDF p <.1 vs HDF % 1 HDx THERANOVA 4 HD FX CORDIAX 8 % 1 HDx with THERANOVA 4 HDF post FX CORDIAX * 17 Da 225 Da 24 Da 33 Da YKL-4 4 Da 45 Da 17 Da 225 Da 24 Da 33 Da YKL-4 4 Da 45 Da Do not use THERANOVA dialyzers for HDF or HF due to higher permeability of larger molecular weight proteins such as albumin. PERFORMANCE Enhanced blood purification of a wide range of large middle molecules In two clinical studies, comparing to a last-generation high-flux dialyzer, the use of THERANOVA dialyzer in HD resulted in: Markedly greater clearances and intradialytic reduction ratios than regular HD at ordinary blood flow rates 2 Similar to greater removal in comparison to high-volume HDF 2 Albumin removal limited to between 1 and 4 grams 2 PATIENT Patients requiring higher clearances of larger uremic toxins, without access to HDF FLUID QUALITY It is recommended to run the HDx therapy solution with high quality dialysis fluid. However, the unique structure of the THERANOVA dialyzer membrane, providing high adsorption capacity to bacterial products, presents an effective barrier to endotoxins 21 and enables the HDx therapy solution to be compatible with standard-quality dialysis fluid (ISO or ANSI/AAMI RD62). MONITOR Thanks to the standard design and operating mode of the THERANOVA dialyzer, the HDx therapy solution can be easily implemented on any HD monitor (provided it is equipped with an accurate volumetric UF control system). The compatibility has been verified on a large sample of HD monitors during extensive field tests. 22

6 HDF was born on the need to increase middle molecule removal, at a time when the permeability of high-flux dialysis membranes was more limited. By applying high convective volume, HDF can significantly increase solute clearance within the size range defined by high-flux membrane permeability. HDx can achieve a similar solute removal and beyond in the removal of middle and larger middle molecules, when used on any dialysis machine in standard HD mode, removing the need for the more complex equipment required for convective therapies. The THERANOVA membrane is optimized for trans-membrane transport of large solutes and does not require additional HDF type convection. Do not use THERANOVA dialyzers for HDF or HF due to higher permeability of larger molecular weight proteins such as albumin. HDF PERFORMANCE AND BEYOND Equivalent removal of small and conventional middle molecules Greater removal is possible for large middle molecules Applicable to any patient requiring higher clearance of large uremic toxins AS SIMPLE AS HD HD infrastructure: no need for HDF capable monitors and specific water quality and fluid quality assurance measures 23,24 Avoiding HDF additional running costs: no disposable infusion line, fewer ultrafilters, less dialysis water and less concentrates Avoiding requirement for specialist training and extensive monitoring during therapy delivery 25 For the safe and proper use of this device, please refer to the Instructions for Use.

7 References 1. Vanholder R et al. Once upon a time in dialysis: the last days of Kt/V? Kidney Int. 215;88: Yamamoto S et al. Recent progress in understanding dialysis-related amyloidosis. Bone. 29;45 Suppl 1:S U.S. Renal Data System: USRDS 215 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, MD; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Chmielewski M et al. The peptidic middle molecules: is molecular weight doing the trick? Semin Nephrol. 214;34: Maduell F et al. High-efficiency postdilution online hemodiafiltration reduces all-cause mortality in hemodialysis patients. J Am Soc Nephrol. 213;24: Adapted from Azar AT, Canaud B. Chapter 8: Hemodialysis system. In: Azar T, ed. Modelling and Control of Dialysis Systems. SCI 44. Berlin: Springer-Verlag, Hutchison CA et al. Quantitative assessment of serum and urinary polyclonal free in patients with chronic kidney disease. Clin J Am Soc Nephrol. 28;3: Deppisch RM et al. Complement components as uremic toxins and their potential role as mediators of microinflammation. Kidney Int Suppl. 21 Feb;78:S Duranton F et al. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 212 Jul;23(7): Sakurai K, et al. Biomarkers for evaluation of clinical outcomes of hemodiafiltration. Blood Purif (213); 35 (Suppl.1): Okyay GU, et al. Novel inflammatory marker in dialysis patients: YKL-4. Ther Apher Dial (213); 17: Tattersall JE, et al. Online Hemodiafiltration: Definition, Dose Quantification and Safety Revisited. Nephrol Dial Transplant (213); 22: Hörl W, et al. Hemodialysis Membranes: Interleukins, Biocompatibility, and Middle Molecules. J Am Soc Nephrol (22); 13 (Suppl.1): Boschetti-de-Fierro A, et al. MCO membranes: Enhanced Selectivity in High-Flux Class. Scientific Reports (215); 5: Krause B, et al. Highly selective membranes for blood purification. Euromembrane Congress 215, Abstract E Krause B, et al. Polymeric Membranes for Medical Applications. Chemie Ingenieur Technik (23); 75 (11): Ronco C, et al. Evolution of synthetic membranes for blood purification. Nephrol, Dial Transplant (23); 18 (Suppl.7): Nilsson LG, Beck W and Bosch J. Data on File. White Paper May 213 (USMP/MG3/1452) 19. Baxter. Data on file. Dialyzers Biocompatibility Report Kirsch AH et al. Performance of hemodialysis with novel medium cut-off dialyzers. Nephrol. Dial. Transplant. first published online September 1, 216 doi:1.193/ndt/gfw Hulko M, et al. Dialysis membrane pore size does not determine LPS retention. ERA-EDTA 215, Abstract FP Baxter. Data on file. Theranova Limited Controlled Distribution Report Lebourg L, et al. Online hemodiafiltration: is it really more expensive? Néphrol Thérap (213); Mazairac A, et al. The cost utility of hemodiafiltration versus hemodialysis in the Convective Transport Study. Nephrol Dial Transplant (213); 28: Chapdelaine I, et al. Optimization of the convection volume in online post-dilution hemodiafiltration: practical and technical issues. Clin Kidney J (215); 8: DISTRIBUTOR Baxter Healthcare Corporation One Baxter Parkway Deerfield, IL 615 USA MANUFACTURER Gambro Dialysatoren GmbH Holger-Crafoord-Strasse Hechingen Germany Baxter, Making possible personal and Theranova are trademarks of Baxter International Inc. or its subsidiaries. Cordiax is a trademark of Fresenius Medical Care Deutschland GmbH. EUMP/MG29/16-12 August 216 (1)

HDx THERAPY. Enabled by. Making possible personal.

HDx THERAPY. Enabled by. Making possible personal. 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)