Preface
High-Volume Hemodiafiltration: A Scientific Foundation for the Future of Dialysis
By Bernard Canaud, MD, PhD*
Emeritus Professor of Medicine, Montpellier University, Montpellier, France
Emeritus Medical Officer, Global Medical Office, Fresenius Medical Care, Bad Homburg, Germany
Despite five decades of innovation, conventional hemodialysis (HD) has reached a therapeutic ceiling in its ability to improve survival and quality of life for patients with end-stage kidney disease (ESKD). Mortality remains unacceptably high, with cardiovascular disease accounting for more than 50% of deaths. While conventional HD removes small solutes such as urea through diffusive transport effectively, it fails to eliminate middle- and large-molecular-weight uremic toxins adequately. These solutes, implicated in chronic inflammation, cardiovascular dysfunction, malnutrition, mineral bone disorders, and immune dysregulation, remain largely uncovered by conventional dialysis, contributing to poor long-term outcomes.
These persistent unmet medical needs, recognized since the 1980s, form the scientific rationale for hemodiafiltration (HDF), and more specifically for post-dilution high-volume HDF (HVHDF). This advanced modality combines diffusive and convective clearance to achieve superior removal of a broader range of uremic toxins, including β2-microglobulin, pro-inflammatory cytokines, and protein-bound solutes. HVHDF offers multiple clinical benefits: improved cardiovascular stability, reduced systemic inflammation, better nutritional status, enhanced patient well-being, and lower incidence of dialysis-related complications. Collectively, these benefits contribute to reducing the burden of kidney replacement therapy (KRT) at the patient, societal, and healthcare system levels.
For patients eligible for kidney transplantation, HVHDF provides a cardio-protective bridge, potentially improving post-transplant outcomes. For those not suitable for transplantation, it offers a more physiologically tolerable and outcome-oriented dialysis option that alleviates treatment burden.
Multiple randomized controlled trials (RCTs), including the landmark CONVINCE study, as well as large-scale registry analyses and individual patient data meta-analyses (IPD-MA), have consistently shown that HVHDF with convective volumes exceeding 23 liters/session is associated with reduced all-cause and cardiovascular mortality. These findings also demonstrate a dose-response relationship, reinforcing the concept that “more is better” when it comes to convective volume delivery.
Fresenius Medical Care’s technological innovations, particularly the development of machines capable of online substitution fluid generation and high-flux dialyzers, have played a pivotal role in advancing the adoption of HVHDF, across Europe, the Asia-Pacific region, Latin America, and beyond, and now enable the introduction of this therapy in the United States. Integrated systems with real-time feedback controls enable the automatic adjustment of the ultrafiltration rate to maintain an optimal filtration fraction of up to 35%, thereby enhancing consistent and efficient convective solute clearance. Simultaneously, the use of substitution fluid, generated online and sterilized through redundant ultrafilters, ensures both microbiological safety and treatment sterility. This access to an unlimited supply of sterile fluid reduces staff workload by simplifying machine handling during priming, rinsing, or administering intravenous boluses, and eliminates the need for additional saline bags during routine operations. Moreover, it contributes to improved biocompatibility of the extracorporeal treatment. In addition, the algorithms that automatically align dialysate flow with blood flow ratio to 1.2, further enhance treatment efficiency while substantially lowering water and electrolyte consumption. This synergy of performance, precision, and sustainability positions HVHDF as the most environmentally responsible and clinically effective modality currently available in KRT.
From an economic perspective, HVHDF aligns closely with the principles of value-based care by optimizing clinical outcomes while reducing overall healthcare resource utilization. It enhances patient-reported outcomes, tends to reduce hospitalization rates, and supports long-term sustainability through more efficient use of water, energy, and dialysis supplies. As such, HVHDF represents not only a significant clinical advancement but also a strategic solution addressing both public health priorities and environmental stewardship in KRT.
In summary, HVHDF should be regarded as the next-generation standard in KRT. It addresses key limitations of conventional HD within routine treatment timeframes and delivers superior clearance across a wider spectrum of uremic toxins. By improving survival, enhancing quality of life, and supporting sustainable practices, HVHDF is highly recognized as an evidence-based and future-oriented dialysis modality. As detailed in this book, Fresenius Medical Care deserves recognition for its pioneering role in the development and global implementation of this innovative therapy, offering patients with ESKD both an optimal bridge to kidney transplantation and a more integrated, outcome-driven continuum of kidney care.
* Prof. Bernard Canaud is internationally recognized as a leading authority on HDF with more than four decades of scientific research and clinical experience involving patients treated outside the United States. Although he does not practice medicine in the U.S., his perspectives on HDF are grounded in a robust body of evidence derived from randomized controlled trials, meta-analyses, and real-world studies, as well as his globally acknowledged clinical expertise. Importantly, the current scientific evidence supporting the efficacy and safety of HDF has been generated entirely in patient populations treated outside the United States. These data reflect real-world clinical practice across Europe, the Asia-Pacific region, Latin America, and other regions where HDF has been widely adopted for over two decades.