Physicians Innovation Middle Molecule Clearance

Advancing Dialysis Through Middle-Molecule Clearance 

Removal of middle molecules during dialysis may be the next step to advancing patient outcomes. To provide high-quality care, DaVita is pursuing expanded hemodialysis (HD) with medium cut-off dialyzers and hemodiafiltration.  

Large Molecular Size

Large Molecular Size

Protein Binding

Protein Binding


Redefining Quality Care: The Clinical Impact of Middle Molecules 

Middle molecules have been correlated with increased inflammation, cardiovascular disease and other complications for patients with kidney failure.i, ii  Today high-flux HD offers modest clearance of middle molecules due to large molecular size and protein binding. 

Pursuing Multiple Pathways to Better Outcomes 

DaVita is exploring every option for patients. While we deploy new hemodialfiltration (HDF) machines to understand their real-world impact, we’re also piloting expanded HD with medium cut-off dialyzers, which could bring advanced care to dialysis patients — potentially faster — using existing technology.  

High-Volume Hemodiafiltration (HDF)

We are deploying an initial pilot of 100 new, FDA-approved HDF machines. This pilot will give us critical insight into U.S. clinical and operational outcomes amid the various changes HDF requires of patients, nephrologists and clinical staff. This will help contribute to the foundational, real-world evidence needed to validate this therapy for U.S. patients. 

Two complementary evaluations will explore the use of medium cut-off dialyzers in dialysis treatments.

Medium Cut-Off Dialyzer to Extend Life (MODEL) is a quality improvement initiative that will examine the survival of U.S. patients treated with medium cut-off dialyzers.

Increasing Medium Molecular Clearance to Improve Recovery and Sleep (“MEMOIRS”) survey is a prospective cohort study of patient-reported outcomes, comparing the experiences of patients treated with medium cut-off versus high-flux dialyzers.  

Advanced Strategies for Middle Molecule Clearance


Medium cut-off dialyzers and hemodiafiltration (HDF) are now becoming more accessible in the U.S. While both options offer enhanced middle-molecule clearance, they also need validation in the context of U.S. dialysis practice to help identify effective, scalable treatment for patients.  

Physician with patient smiling

“Understanding impact is the first step in understanding how new therapies can improve kidney care — and equipping physicians with insights that support their modality decisions for individualized care.”

— Jeff Giullian, MD, Chief Medical Officer, DaVita

Explore the Conversation 

As therapies emerge in the U.S. to address middle molecule clearance, learn how DaVita is thinking about unlocking next-generation dialysis to provide physicians tools and support for improved patient outcomes. 

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Collaborative Innovation

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i Wolley MJ, Hutchison CA. Large Uremic Toxins: An Unsolved Problem in End-Stage Kidney Disease. Nephrology, Dialysis, Transplantation. 2018;33(suppl_3):iii6-iii11. 

ii Fatigue in Patients Receiving Maintenance Hemodialysis: A Review. Bossola, Maurizio et al. American Journal of Kidney Diseases, Volume 82, Issue 4, 464 – 480