I am always amazed how ‘comfortable’ I am in a dialysis center.

It no longer confounds me that we are taking a person’s blood out of his or her body and circulating it through plastic tubing and a dialyzer (which is really nothing but a plastic membrane, often in hollow “pipe” configuration or as a sandwich with blood at the center) for hours. In essence, because the patient’s kidneys are failing to do so,  we are circulating the patient’s entire blood volume through this circuit 20 complete times to remove the toxins of daily living.

That should give anyone pause.  But, after 50 years, I’ve become inured to the concept.  Except I know that the patient also gets a bolus of heparin each treatment, along with continued infusion of the blood-clotting-blocker.  This ensures the patient’s blood doesn’t react with the tubing or the dialyzer, blocking blood flow through the extracorporeal circuit.   And, as is true any time we add a drug to the mix, there are potential side effects.  In this case- lower platelet counts, higher cholesterol, and/or osteoporosis.

Which is why Evonik and Invizius, among others, have been developing technology to preclude adhesion onto extracorporeal systems and the activation of blood proteins or components- all to block the formation of thrombi (blood clots).  In so doing, either eliminating or reducing the need for the heparin infusions.

Back at the turn of the century,  Dr. Paul Senterre (U Toronto) began developing anti-thrombotic additives for polyurethane- which use he has since been extended to other plastics.  Using low molecular weight (fluoro-oligomeric) additives, infused into the plastic (1 to 5% of the total material), he developed what he termed “Endexo” technology to preclude the need for heparin.  These additives migrate to the top few nanometers of the device during curing [production]; in so doing, these additives afford the polymer significant surface modifications.

The modified surfaces achieve the results Dr. Senterre desired- they suppress the coagulation of proteins and platelet adhesion, plus they inhibit the activation of platelets.  That means that thrombosis and biofouling are precluded- without the need for heparin- or at least afford a significant reduction in heparin use.

Like any good professor-inventor, Dr. Senterre was instrumental in the formation of Interface Biologics, the corporate vehicle that would offer his inventions to the world.  Recently, Interface Biologics licensed their medtech technology to Evonik, with one market exception.

The Endexo technology is now licensed to three companies- AngioDynamics, which business relates to vascular access devices, Arkis BioSciences for neurology, and Fresenius Medical Care, the largest provider of dialysis in the world. (Interface Biologics retained this license arrangement directly with Fresenius.)

AngioDynamics received FDA clearance more than 6 years ago for its central venous catheters and ports.  Arkis BioSciences got the go ahead for their neurologic catheters.  And, now, Fresenius has demonstrated to the FDA that its employment of the Endexo technology is safe and effective for dialysis patients. So, that means folks using their dialysis circuit and dialyzers will still need heparin- but at much lower dosages for their four hour treatment.

Of course, there is another change required for the Endexo dialysis technology.  Bicarbonate dialysis relies on a small amount of acetic acid to control the pH properly.  The acetate component will now be replaced by citric acid (which becomes a citrate after reaction).  (Fresenius calls their hemodialysis solutions “Citrasate”.)  Citrate  is thought to be beneficial in precluding vascular calcification (compared to acetate), but with only 3-4 mEq/L (maximum) contacting the blood, it probably has little different effect on the blood- but may have more effect on the Endexo technology.

Invizius uses a different approach to reduce thrombosis.  This product is a spinoff from the University of Edinburgh (Scotland) under the direction of Dr. Andy Herbert (and his then PhD student, Dr.  Eliza Makou).  Their approach is to infuse a sticky-protein laden solution [which they call H-guard] into the dialysis circuit.  This then dampens the blood’s inflammatory responses during dialysis.

They call their solution H-guard because of factor H, a key protein component in blood.  This soluble factor supresses recognition of surfaces, so coagulation can be precluded.  Note that clinical trials have not yet started, but they have obtained funding to do so.  (They also hope to extend the use of the solution for stents, grafts, as well as heart and lung devices.)