Hemodiafiltration: A nephrologist offers a comprehensive review
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When discussing dialysis physiology, I often make the joke that convection plus diffusion leads to confusion.
Unfortunately, it is so with American nephrologists. Our only valid experience with convective solute transport is during continuous renal replacement therapy using the hemofiltration mode. I visited nephrologists Charles Mion, MD, and Bernard Canaud, MD, in Montpellier, France, in 1990 as they were developing online sterile substitution (replacement) fluids for hemofiltration. Their strategy was to siphon off ultraclean dialysate from the inflow system, sterilize it by filtration and then use it as substitution fluid for a high volume of ultrafiltration during the hemodialysis (HD) session.
Thus, a simultaneous application of convection and diffusion occurs in a process called hemodiafiltration (HDF). The substitution fluid was produced online, hence the term “online HDF.”
For decades, nephrologists outside the United States applied HDF in clinical practice. A 2004 joint NIH-FDA dialysis water purity conference failed to convince the FDA that filtration is an adequate water sterilizing technique. However, through industry and other research efforts, the FDA eventually began to accept that online HDF might be an alternative to current HD. Fresenius Medical Care recently received 510(k) clinical trial clearance for its 5008X Hemodialysis System and companion FXCorAL dialyzer.
Acceptance
When available, will U.S. nephrologists accept HDF? I think the inexperience by dialysis providers and the cost of converting equipment and dialyzers to perform online HDF will be key factors.
The comorbidity burden of American patients on dialysis has historically been higher than that seen in other countries. We have attributed U.S. survival rates to this difference and complacently have not emphasized other explanations, such as water and/or technique quality.
The dialysis experience in Tassin, France, is an example. The approach of Bernard Charra, MD, was a long HD session that slowed the ultrafiltration rate, facilitating greater and more tolerable water and sodium removal. It also enhanced removal of larger solutes, for which dialysis is time dependent.
In the United States, we were doing the opposite, promoting efficiency as determined by dialyzing more patients with a shorter but aggressive session using larger surface area dialyzers, greater extracorporeal blood commitments, higher blood flow rates and shorter treatment times.
The greatest expense of an in-center HD treatment is labor. At a fixed treatment payment, reducing labor expenses became important and “high efficiency” achieved this.
Quality measures
Congress mandated that CMS determine metrics that would be considered as surrogates for demonstration of dialysis quality. We became preoccupied with achieving these metrics. Simultaneously, our international colleagues were investing in improving techniques, applying a Tassin lesson that removing larger molecules may enhance survival. Convective transport and time are known to relatively increase larger molecule removal compared with small molecules such as urea. Thus, hemofiltration and the hybrid HDF therapies were applied and have methodically evolved.
There are many variations to the techniques including the access blood flow rate, the source of the substitution fluid, the site(s) of its administration and the amount (volume) per session.
Most U.S. nephrologists have minimal experience with convective depuration. This reflects the inadequacies of dialysis science education during fellowship and provides a similar explanation for the underutilization of home dialysis.
However, there are still barriers even if U.S. nephrologists were anxious to utilize HDF (see Sidebar “Hemodiafiltration on American shores”).
High convective volume online HDF is a superior therapy to high flux HD. It will be more expensive in the short run but if hospitalizations are reduced, perhaps it will be less expensive in the long run. A cynical view is longer survival is expensive as well. A big problem is inexperience, and a starting point is to use medium cutoff membrane dialyzers. While that will mildly increase expenses, it may help convince the kidney care community that modern dialysis alternatives are actual advancements in medical care.
- References:
- Blankestijn PJ, et al. N Engl J Med. 2023;doi:10.1056/ NEJMoa2304820.
- Caskey FJ, et al. Trials. 2022;doi:10.1186/s13063-022-06357-y.
- Charra B, et al. Am J Kid Dis. 1998;doi:10.1016/S0272-6386(98)70164-7.
- Drüeke TB, et al. Kid Intern. 2023;doi:10.1016/j.kint.2023.07.012.
- Golper TA. New Engl J. Med. 2023;doi:10.1056/NEJMe2307709.
- Guimarães MGM, et al. Kidney Medicine. 2024;doi:10.1016/j.xkme.2024.100829.
- Hornig C, et al. Semin. Dial. 2022;doi:10.1111/sdi.13075.
- Mayne KJ, et al. Clinical Kidney Journal. 2023;doi:10.1093/ckj/sfad258.
- Nistor I, et al. Cochrane Database Syst Rev. 2015;doi:10.1002/14651858.CD006258.pub2.
- Shroff R, et al Nephrol Dial Transplant. 2023;doi:10.1093/ndt/gfad136.
- Strippoli GFM, et al. Clinical Kidney Journal. 2024,doi:10.1093/ckj/sfae035.
- Ward RA, et al. Clin J Am Soc Nephrol. 2018;doi:10.2215/CJN.12641117.
- For more information:
- Thomas A. Golper, MD, FACP, FASN, is emeritus professor of medicine at Vanderbilt University Medical Center and professor of medicine at Larner College of Medicine at the University of Vermont. He is also emeritus chair of the Editorial Advisory Board of Healio | Nephrology News & Issues. He can be reached at thomas.golper@vumc.org.
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