Hemofiltration

In medicine, hemofiltration, also haemofiltration, is a renal replacement therapy similar to hemodialysis which is used almost exclusively in the intensive care setting. Thus, it is almost always used for acute renal failure. It is a slow continuous therapy in which sessions usually last between 12 to 24 hours and are usually performed daily. During hemofiltration, a patient's blood is passed through a set of tubing (a filtration circuit) via a machine to a semipermeable membrane (the filter) where waste products and water are removed. Replacement fluid is added and the blood is returned to the patient.

The principle of hemofiltration
As in dialysis, in hemofiltration one achieves movement of solutes across a semi-permeable membrane. However, solute movement with hemofiltration is governed by convection rather than by diffusion. With hemofiltration, dialysate is not used. Instead, a positive hydrostatic pressure drives water and solutes across the filter membrane from the blood compartment to the filtrate compartment, from which it is drained. Solutes, both small and large, get dragged through the membrane at a similar rate by the flow of water that has been engendered by the hydrostatic pressure. Thus convection overcomes the reduced removal rate of larger solutes (due to their slow speed of diffusion) seen in hemodialysis.

Replacement fluid composition
An isotonic replacement fluid is added to the blood to replace fluid volume and electrolytes. The replacement fluid must be of high purity, because it is infused directly into the blood line of the extracorporeal circuit. The replacement hemofiltration fluid usually contains lactate or acetate as a bicarbonate-generating base, or bicarbonate itself. Use of lactate can occasionally be troublesome in patients with lactic acidosis or with severe liver disease, because in such cases the conversion of lactate to bicarbonate can be impaired. In such patients use of bicarbonate as a base is preferred.

Hemodiafiltration
Hemofiltration is sometimes used in combination with hemodialysis, when it is termed hemodiafiltration. Blood is pumped through the blood compartment of a high flux dialyzer, and a high rate of ultrafiltration is used, so there is a high rate of movement of water and solutes from blood to dialysate that must be replaced by substitution fluid that is infused directly into the blood line. However, dialysis solution is also run through the dialysate compartment of the dialyzer. The combination is theoretically useful because it results in good removal of both large and small molecular weight solutes.

Intermittent vs. continuous modes of therapy
These treatments can be given intermittently, or continuously. The latter is usually done in an intensive care unit setting.

On-line intermittent hemofiltration (IHF) or hemodiafiltration (IHDF)
Either of these treatments can be given in outpatient dialysis units, three or more times a week, usually 3–5 hours per treatment. IHDF is used almost exclusively, with only a few centers using IHF. With both IHF or IHDF, the substitution fluid is prepared on-line from dialysis solution by running dialysis solution through a set of two membranes to purify it before infusing it directly into the blood line. In the United States, regulatory agencies have not yet approved on-line creation of substitution fluid because of concerns about its purity. For this reason, hemodiafiltration, had historically never been used in an outpatient setting in the United States. However, on April 30. 2012, Nephros, Inc. (NEPH.OB), a medical device company developing and marketing filtration products for therapeutic applications and advanced water purification solutions, announced the Company had received 510(k) clearance from the Food and Drug Administration ("FDA") to market its Hemodiafiltration ("HDF") system for the treatment of chronic renal failure when used with UF controlled dialysis machines capable of producing ultrapure dialysate in accordance with current AAMI/ANSI/ISO standards in the United States.

The system is composed of Nephros's OLpur MD220 Hemodiafilter and Nephros's OLpur H2H Hemodiafiltration module. Nephros's OLpur MD220 Hemodiafilter is a dialyzer designed expressly for HDF therapy that employs Nephros's proprietary Mid-Dilution Hemodiafiltration technology. Nephros's OLpur H2H Hemodiafiltration module is intended for use with UF controlled dialysis machines capable of producing ultrapure dialysate in accordance with current AAMI/ANSI/ISO standards.

"HDF represents an alternative treatment option for chronic renal failure, and I am excited that patients in the United States will now have the opportunity to be treated with this important therapy," said Leonard Stern, M.D., Medical Director at Columbia University Dialysis Center, and Associate Clinical Professor of Medicine, Columbia University, College of Physician and Surgeons.

"Nephros can now offer the only on-line HDF therapy available in the U.S.," said John C. Houghton, President & CEO of Nephros, Inc.

Continuous hemofiltration (CHF) or hemodiafiltration (CHDF)
Hemofiltration is most commonly used in an intensive care unit setting, where it is either given as 8–12 hours treatments, so called SLEF (slow extended hemofiltration), or as CHF (continuous hemofiltration also sometimes called continuous veno-venous hemofiltration (CVVH)) or Continuous Renal Replacement Therapy (CRRT). Hemodiafiltration (SLED-F or CHDF or CVVHDF) also is widely used in this fashion. In the United States, the substitution fluid used in CHF or CHDF is commercially prepared, prepackaged, and sterile (or sometimes is prepared in the local hospital pharmacy), avoiding regulatory issues of on-line creation of replacement fluid from dialysis solution.

With slow continuous therapies, the blood flow rates are usually in the range of 100-200 ml/min, and access is usually achieved through a central venous catheter placed in one of the large central veins. In such cases a blood pump is used to drive blood flow through the filter. Native access for hemodialysis (e.g. AV fistulas or grafts) are unsuitable for CHF because the prolonged residence of the access needles required might damage such accesses.

Is on-line intermittent hemodiafiltration (IHDF) better than regular hemodialysis?
There is controversy about whether intermittent on-line hemodiafiltration (IHDF) gives better results than hemodialysis in an outpatient setting. In Europe, several observational studies have compared outcomes in patients getting dialysis with those getting IHDF.

Based on data from two studies, Fresenius Medical Care announced an increased effectiveness of online hemodiafiltration (OL-HDF) modality in the treatment of patients with renal failure. The findings of two multicenter trials were presented in a scientific symposium that took place during the 2011 European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) congress in Prague, Czech Republic (June 23-26). The evidence presented resulted from examining the survival rates of dialysis patients treated with OL-HDF, a treatment method recognized for higher efficiency in removing  uremic toxins from the blood of patients with renal failure.

In a study involving 782 patients in 10 dialysis clinics conducted in Turkey under the direction of Professor Ercan Ok at the EGE University in Izmir, patients treated with high-volume HDF displayed a better chance of survival compared to those treated with high-flux dialysis. Patients treated with substitution volumes greater than the median of 17.4 liters showed a 46% lower overall risk of mortality during the two-year study. Moreover, patients treated with OL-HDF required 20% lower dosage of erythropoiesis-stimulating agents (EPO) than patients in the high-flux group while maintaining the hemoglobin level at 11.5 g/dl. Ok’s findings, based on a prospective, controlled, randomized clinical study, confirm the results of two previous observations supported by data analyzed from thousands of patients.

Another multicenter trial (CONTRAST; CONvective TRAnsport STudy) presented in Prague compared OL-HDF with low-flux dialysis. Conducted in three countries, its results also showed that patients treated with higher substitution volumes displayed a survival benefit.

The use of OL-HDF is increasing worldwide, with 15% of dialysis patients in Europe already benefiting from the advanced treatment option to which numerous other advantages are attributed. Several publications report reduced morbidity and improved patient well-being. Improved anemia and blood-pressure control as well as reduced inflammation, the underlying mechanism of many chronic diseases, are just some of the reported benefits that may contribute toward improved patient survival with OL-HDF.

Fresenius Medical Care has been a pioneer in advancing HDF therapy and has developed its 5008 therapy system and new Cordiax dialyzers specifically to facilitate this treatment option. In Fresenius Medical Care’s European  dialysis centers, over 50% of the patients already receive HDF treatment.

“The positive results of these new studies validate our efforts to offer innovative dialysis products and advanced therapies such as hemodiafiltration. Based on the new study findings, we plan to further increase application of this therapy substantially in the future,” said Dr. Emanuele Gatti, Fresenius Medical Care CEO for Europe, Latin America, the Middle East and Africa. "We are proud that the study performed under the direction of Professor Ok used dialysis centers operated by  Fresenius Medical Care. And we shall continue to strive for improved outcomes of chronic kidney disease patients who depend on  dialysis therapies,” he added.

Fresenius HDF therapy, however, has not been approved by the FDA for use in the United States. The FDA has not determined their system to be safe enough for their standards. Alternatively, the Nephros OLpur MD220 Hemodiafilter and Nephros's OLpur H2H Hemodiafiltration module have been approved by the FDA. Nephros's OLpur MD220 Hemodiafilter is a dialyzer designed expressly for HDF therapy that employs Nephros's proprietary Mid-Dilution Hemodiafiltration technology. Nephros's OLpur H2H Hemodiafiltration module is intended for use with UF controlled dialysis machines capable of producing ultrapure dialysate in accordance with current AAMI/ANSI/ISO standards Source: PR Newswire (http://s.tt/1atlu)

A recent study asses the better outfit of patients treated with OL-HDF rather than standard HD http://jasn.asnjournals.org/content/early/2013/02/13/ASN.2012080875.full