The nephrology community has long taken to improve conventional HD treatment outcomes and tolerability, while preserving treatment safety and center workflow efficiency.7 As clinical expectations have risen, so too have patients’ desire for therapies that better support longevity, tolerability, and day-to-day well-being.7
Across the globe, clinicians have responded to these challenges by adopting more advanced dialysis modalities. One of the most promising among them, high-volume hemodiafiltration, has been associated with meaningful improvements in survival, symptom burden, and patient-reported quality of life.8–10
High-volume HDF has recently been made available in the U.S. and offers an alternative therapy to meaningfully advance In-Center patient care.11*
Recognized shortcomings of conventional hemodialysis
Conventional in-center hemodialysis (HD) relies primarily on diffusion to remove uremic toxins. Diffusion is highly effective for clearing small solutes such as urea, but less effective for larger middle-molecule toxins — compounds such as β2-microglobulin, inflammatory mediators, and protein-bound solutes. These molecules accumulate between dialysis treatments and are increasingly recognized as contributors to cardiovascular disease, inflammation, and impaired functional status.
Several well-documented challenges persist with conventional HD, including:
- High mortality rates: Despite advances in fluid management and infection control, mortality among U.S. in-center HD patients remains high, particularly from cardiovascular causes.4
- Frequent hospitalizations: Fluid overload, infections, and cardiovascular instability contribute to hospitalization rates that exceed those of many other chronic diseases.4
- Intradialytic hypotension: Episodes of low blood pressure during treatment are common and can lead to fatigue, nausea, cramping, and increased risk of cardiac events.12,13
- Poor treatment tolerance: Those with autonomic dysfunction, heart failure, or advanced age may struggle with the rapid fluid and solute shifts inherent to conventional HD.14
- Limited clearance of middle molecules: Diffusion alone cannot adequately remove larger uremic toxins, leaving people vulnerable to chronic inflammation, amyloidosis, and reduced quality of life.14
These challenges have prompted clinicians and researchers to explore therapies that more closely aligned to the kidney's natural ability to clear a broad spectrum of solutes while maintaining hemodynamic stability.
What is high-volume HDF?
High-volume hemodiafiltration represents a meaningful advancement for in-center dialysis patient care. HDF combines diffusion and convection to improve uremic toxin removal across a wider molecular range.
Convection relies on high ultrafiltration rates to transport solutes across a high-flux dialyzer membrane, a process often described as solvent drag. This mechanism enables efficient removal of large middle molecules while preserving essential plasma proteins. To maintain hemodynamic stability, the fluid removed during treatment is replaced downstream of the dialyzer with online generated, sterile, non-pyrogenic substitution fluid before the blood is returned to the patient.
A defining feature of HDF is the convection volume, which represents the total ultrafiltration achieved during a session. Convection volume is calculated as the sum of the patient’s intradialytic weight loss and the volume of substitution fluid delivered.
Clinical studies have consistently shown that achieving convective volumes of ≥23 L per session, or HighVolumeHDF (HVHDF), is associated with greater therapeutic benefit.8–10 Evidence demonstrates a dose–response relationship, with higher delivered convection volumes correlated with improved clinical outcomes.15
With the introduction of HDF technology in the U.S., the ability to generate sterile, nonpyrogenic substitution fluid on demand now makes it possible to safely deliver the high convective volumes required for HVHDF. This capability supports enhanced convective transport and enables the removal of a broader spectrum of toxins, advancing the treatment clearance profiles closer to the kidney’s natural filtration function.
High-volume HDF and mortality benefit
Randomized controlled trials have demonstrated that high-volume HDF is associated with a meaningful reduction in mortality compared with conventional high-flux hemodialysis. In the CONVINCE trial,* 92% of sessions achieved convection volumes of ≥23 L. Patients treated with HDF, experienced a 23% reduction in all-cause mortality (hazard ratio 0.77; 95% CI, 0.65–0.93).10 Large real-world datasets involving more than 80,000 patients have shown a similar decrease in mortality risk, reinforcing that these benefits extend beyond controlled research settings.9
Subsequent meta-analyses have supported these findings, demonstrating survival advantages when convection volumes of ≥23 L per session are achieved.15 Collectively, the evidence supports high-volume HDF as a therapy with measurable and reproducible mortality benefits over standard high-flux hemodialysis.
Patient reported outcomes and quality of life with High-volume HDF
Quality-of-life outcomes have become increasingly critical in clinical decision-making in nephrology. Patients value symptom relief and day-to-day well-being as much as, if not more than, mortality and hospitalization.16 The CONVINCE trial offers important insights by demonstrating that high-volume HDF not only correlates with improved survival but also meaningfully preserved patient-reported quality of life.
In CONVINCE, patients receiving high-volume HDF vs. high-flux HD reported improvements across multiple KDQOL domains, including:8
- Slower decline in cognitive and physical functions
- Extended ability for social participation
- Reduced interference with daily activities due to pain
- Better preservation of physical activity levels
These gains are notable because fatigue, cramping, and post-treatment malaise have remained pervasive for many patients treated with conventional high-flux hemodialysis.5,6
Across patient-reported outcome studies, some patients receiving high-volume HDF report:†
- Less cramping and intradialytic hypotension and better treatment tolerability12
- Less post-treatment fatigue17
- Potential for improved protein intake and preservation of lean body mass18
High-volume HDF is also associated with fewer hospitalizations and shorter hospital stays19,20 and shorter post-dialysis recovery time.21†
Importantly, the quality-of-life benefits observed in CONVINCE and other studies demonstrate improvements in how patients feel and function, aligning treatment more closely with patient-centered goals.6
High-volume HDF: Transforming the standard of In-Center dialysis care
High‑volume HDF represents more than an incremental improvement in dialysis technology—it marks a meaningful shift toward therapies that better reflect what patients want and need from their treatment. By expanding solute clearance, and demonstrating benefits in both survival and quality‑of‑life outcomes, high-volume HDF advances what is possible to achieve for in‑center patients.8,10,14
The therapy has been widely adopted across Europe, Asia, and Latin America, where clinicians have embraced it for its survival benefits and quality of life advantages.22 As high‑volume HDF adoption grows in the U.S., it has the potential to redefine the standard of dialysis care by aligning clinical practice with the evolving expectations of patients and clinicians alike, ultimately helping more people living with ESKD feel better and live longer.8–10‡
Learn More About High-Volume HDF
Explore the clinical evidence behind high-volume hemodiafiltration, including survival outcomes, patient-reported benefits, and treatment delivery requirements.
View Clinical Evidence.
