In Germany in the mid-1970s, Fresenius AG (whose dialysis division would become FME in 1996) focused its efforts on two major initiatives: the development of equipment for hemofiltration (HF) and the creation of a new-generation hemodialysis (HD) system, which ultimately led to the introduction of the A2008 (1).<\/p>\n
While the HD project, being more complex, took precedence, HF development remained limited to manually controlled setups combining existing components.<\/p>\n
In 1976, contacts with the research team of Leber and Wizemann, based at the University Hospital in Giessen, Germany, introduced Fresenius AG to their pioneering work on HDF (2).<\/p>\n
FME recognized the potential of integrating their advanced A2008 HD system with Sartorius\u2019s Haemoprocessor. This collaboration led to the creation of the first commercially available HDF system in Europe, the ABG-1 (1). This system utilized the A2008\u2019s closed hydraulic circuit, which proved ideal for extending its capabilities to HDF, a feature still benefiting FME machines today. The ABG-1 featured modifications such as a substitution fluid heater and pump alongside Sartorius\u2019s automatic balancing device (Figure 1.1).<\/p>\n
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Figure 1.1. | Fresenius A2008C with the ABG-1 hemodiafiltration module, a joint development of Fresenius AG (Bad Homburg, Germany) and Sartorius AG (Gottingen, Germany). Source FME R&D archive.<\/span><\/p>\n The A2008C machine, equipped with its advanced volumetric fluid-balancing system, provided an ideal platform for integrating not only high-flux and HDF procedures but also the capability for online fluid preparation. Figure 1.2 presents a facsimile of a 1986 directive from Gerd Krick, mandating the acceleration and completion of the development and market introduction of an online HDF system (1).<\/p>\n A subsequent version, the ABG-II, was developed exclusively by Fresenius AG. The company’s position was further strengthened by developing a polysulfone dialysis membrane. This new synthetic high-flux membrane set the benchmark for future synthetic membranes, offering high hydraulic permeability, superior biocompatibility, enhanced clearance of small and middle molecules, and a reduced risk of bacterial contamination.<\/p>\n The attenuation of bacterial contamination was a critical advancement, facilitating the development of a new generation of ultrafilters. These ultrafilters enabled the production of online substitution fluid directly from standard dialysate, thereby making online HDF feasible.<\/p>\n The dialysate ultrafilters, later marketed under the DIASAFE\u00ae<\/sup>plus<\/em> brand, were progressively optimized for integration with FME dialysis machines. This system generated sterile substitution fluid directly from dialysate via a cold multi-stage ultrafiltration process, ensuring consistent quality and safety while eliminating the need for prepackaged sterile fluids.<\/p>\n Figure 1.2 | Written order and rationale by Fresenius AG Board Member Dr. G. Krick to boost and finish the development of the scientific, medical, and technical basis for a commercial online HDF system released in 1986 (1). Source: FME R&D archive Author translation: \u2018I believe there is agreement that online HDF in future will play an important role in the treatment of acute or chronic kidney patients; in this sense high-flux dialysis with highly permeable membranes is just a preliminary stage. For Fresenius as initiator of hemodiafiltration it is of outermost importance to belong to the pioneers of high-flux dialysis and on-line HDF again, especially because we have a much better position compared to nearly all competitors due to the new polysulfone membrane. We meanwhile agreed that \u2013 effective January 1st, 1986 and without any constraints \u2013 you will be responsible for the medical and scientific concept of an online HDF. This task includes (a) back filtration, (b) sterile and pyrogen filtration, (c) the question of IL- 1 generation, (d) the general improvement of dialysis by means of \u2018infusion\u2019. The technical part of online HDF is addressed already in R&D Medical Devices by Dr. Polaschegg and his co-workers. Concepts to solve the technical problems already are available\u2026. In case you face any problems during your work, including problems regarding cooperation with in-house employees, you are asked to inform me immediately…\u2019 (1)<\/span><\/p>\n In 1987, Fresenius AG introduced its first approved and commercially available online HDF system in Europe (Figure 1.3), initially developed and approved by the German T\u00dcV in its 1985 version.<\/p>\n Figure 1.3. | First approved and commercially available Fresenius online HDF system for the HD machine A2008C(1987) and German approval. Source FME R&D archive.<\/span><\/p>\n In 1998, the 4008H dialysis machine offered ONLINEplus\u2122 technology as an optional feature outside the U.S. This technology enabled HVHDF by producing sterile substitution fluid directly from dialysate during treatment (Figure 1.4). The integration of this feature enhanced the machine’s versatility, making it suitable for both conventional HD and online HDF while maintaining stringent standards for fluid sterility and treatment safety. This optional upgrade marked a significant step toward optimizing dialysis treatments for improved patient outcomes.<\/p>\n Figure 1.4. | Fresenius Medical Care 4008 H dialysis machine. Source: FME R&D archive.<\/span><\/p>\n Building upon this innovation, in 2005, following two decades of research and development, FME established online HDF as a standard feature in its 5008 dialysis machine outside the U.S. (Figure 1.5) (1, 3). This decision highlighted the growing appreciation of HDF’s clinical superiority over conventional high-flux HD, supported by a growing body of real-world evidence (RWE) (4, 5).<\/p>\n Figure 1.5 | FME 5008 dialysis machine. Source: FME Care Enablement.<\/span><\/p>\n The evolution of dialysis technology led to the development of the 5008 and 6008 series machines (including the 5008X, the first Fresenius Medical Care device capable of performing online HDF in the U.S. market), which incorporate advanced features to enhance both treatment efficacy and operational efficiency. These innovations included automatic online fluid preparation, improved convective clearance, and optimized resource utilization, reducing costs compared to standalone HDF platforms. Furthermore, the 5008 and 6008 series machines were designed with an intuitive user interface, facilitating seamless operation and real-time monitoring. Their enhanced usability and accessibility improve treatment accuracy and workflow efficiency (Figure 1.6).<\/p>\n Figure 1.6 | Fresenius 5008S Cordiax (A), 5008X (B), and 6008 (C) dialysis machines. Source: FME archive.<\/span><\/p>\n Additionally, in 2005, HDF was established as standard therapy in FME Europe, the Middle East, and Africa (EMEA) NephroCare clinics (6).<\/p>\n FME has continued to advance technologies such as HDF by integrating clinical excellence with cutting-edge technical innovation. In his former role as EMEA Chief Medical Officer, Bernard Canaud<\/em> played a pivotal role in redefining the standards of care for patients with ESKD. His work was instrumental in developing an early and robust evidence base demonstrating HDF as a superior KRT, significantly improving both intermediate and long-term patient outcomes compared to conventional high-flux HD in patients in EMEA (7-30).<\/p>\n FME medical leadership, including key figures such as Frank Maddux<\/em>, Global Chief Medical Officer, and Stefano Stuard<\/em>, Global Clinical Officer for HDF, has been instrumental in establishing and upholding the highest medical standards for HDF treatments.<\/p>\n In 2014, post-dilution HVHDF was formally recognized as the gold standard in FME EMEA NephroCare clinics. This milestone was accompanied by the implementation of an HDF-specific key performance indicator (KPI), which set a target convective clearance volume for EMEA NephroCare clinics. The KPI mandated substitution volumes of \u2265 21 liters per session enabled HVHDF to be delivered at an optimal convective volume of \u2265 23 liters per session. By 2023, more than 62% of all HD patients in FME EMEA clinics were receiving HDF, with over 26,000 patients undergoing post-dilution HVHDF. These patients achieved a mean convective volume of 27.4 \u00b1 4.9 liters per session, underscoring FME\u2019s operational excellence and commitment to delivering superior renal care (29).<\/p>\n The FME Global Medical Office has conducted numerous retrospective studies in patients dialyzed in FME EMEA NephroCare clinics, supporting the superiority of HVHDF over conventional HD (7, 13, 23, 31-34), a finding repeatedly confirmed by randomized prospective controlled trials such as CONTRAST, Turkish, ESHOL, and CONVINCE (35-38). Several studies have demonstrated a dose-response relationship between substitution\/convective volume and relative survival rate, with comparable results (30, 39-41). Specifically, a substitution\/convective volume exceeding 21\/23 L per session, respectively, has exhibited the most favorable effect on mortality outcomes (42-44).<\/p>\n Despite the widespread implementation of online HDF in Europe for several decades and its more recent adoption in Asia, its utilization in the United States has been minimal. This limited uptake can be attributed to several factors, including potential skepticism of the results of the randomized controlled trials (RCTs) prior to CONVINCE (38), the increased technical complexity of HDF compared to HD, particularly regarding water management systems, and structural differences in healthcare delivery and reimbursement models. It also required a dialysis machine capable of online fluid generation, which was previously unavailable in the U.S. Furthermore, the successful integration of HDF requires the development of specialized training programs and operational frameworks, necessitating adaptations within the healthcare infrastructure and in medical education and professional training systems.<\/p>\n FME in EMEA has been instrumental in advancing HVHDF by contributing to patient-reported outcomes research and cost-effectiveness analyses, underscoring HVHDF\u2019s value in improving quality of life and reducing long-term healthcare costs. FME consistently focuses on enhancing the sustainability of HVHDF by optimizing water and resource utilization in dialysis treatments. Advances in machine technology and the enhanced HVHDF prescription have reduced total water consumption (29). Waste reduction, improved energy efficiency, and aligning HVHDF with “green dialysis” is also an important goal.<\/p>\n In addition to its technical contributions and high operational quality standards, FME emphasized the importance of continuous medical education and training. Recognizing the complexities of HVHDF, the company championed educational programs to empower nephrologists, clinical staff, and healthcare teams with the knowledge and skills to deliver this advanced therapy safely and effectively, a key requirement for establishing confidence in the nephrologist\u2019s ability to prescribe and manage HVHDF therapy.<\/p>\n The following strategic steps for FME will focus on implementing and expanding HVHDF in countries where its adoption remains limited to a minority of ESKD patients due to regulatory restrictions, reimbursement challenges, and healthcare system constraints (45).<\/p>\n Addressing these barriers will ensure wider access to HVHDF and its well-documented clinical benefits, thereby elevating the standard of care for ESKD patients worldwide. FME, with its expertise in dialysis technologies and quality operational excellence, is positioned to lead the adoption of HVHDF in the U.S. through the strategic deployment of the 5008X dialysis machine and FX CorAL dialyzers \u2014 devices specifically designed to facilitate the implementation of this therapy. The primary focus of this expansion will be the United States, where the transition to HVHDF aligns with current clinical demands and value-based care objectives. The FME EMEA region, with its proven success in HVHDF adoption, will serve as a benchmark. Sharing this region’s best practices and clinical outcomes will inform U.S. strategies and other global markets.<\/p>\n In February 2024, FME received U.S. Food & Drug Administration (FDA) 510(k) clearance\u00a0 for the 5008X hemodialysis system (46). Following FDA clearance, FME reached a significant milestone in KRT in the U.S. on January 24, 2025. The first HVHDF (convective volume > 23 Liters\/session) was successfully performed at a Fresenius Kidney Care (FKC) clinic in Wellesley, MA. This landmark session demonstrated the clinical feasibility of implementing HVHDF in the U.S. healthcare setting and achieved an impressive substitution volume of 25.5 liters over 215 minutes of HDF treatment (Figure 1.7).<\/p>\n Figure. 1.7 | First U.S. ESKD patient treated with HVHDF and 5008X hemodialysis system, achieving a substitution volume of 25.5 L per session<\/strong>. The HVHDF treatment was performed at the FKC clinic in Wellesley, Massachusetts, on January 24, 2025.<\/span><\/p>\n This milestone represents a critical therapeutic advancement in KRT in a generation to patients in the U.S., signifying a breakthrough for the nephrology community.<\/p>\n <\/p>\n","protected":false},"featured_media":0,"template":"","format":"standard","meta":{"_acf_changed":false},"categories":[5],"tags":[296],"language":[41],"articles":[162],"class_list":["post-7849","article","type-article","status-publish","format-standard","hentry","category-articles","tag-handbook-hdf","language-english","articles-hemodiafiltration","entry","no-media"],"acf":[],"yoast_head":"\n![\"\"](\"https:\/\/ami.advancedrenaleducation.com\/wparep\/wp-content\/uploads\/2025\/07\/figure1.2.png\")
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\n A<\/td>\n B<\/td>\n C<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n 1.2\u00a0 | Educational initiatives<\/h2>\n
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