I have been following this thread with interest for the past couple of months and based primarily on Debby’s comments, I now feel compelled to contribute regarding the comparison of the Aksys PHD system to the NxStage System One. I am a Certified Nephrology Nurse with more years of experience in the business of dialysis than I care to admit. I have worked for several different dialysis companies including Aksys for a short time but that was a while ago. First I’d like to tackle the subject of backflushes which Debby reports had an adverse effect on her.
To preface this discussion, the participants on this thread should understand that the NxStage product was not originally designed for daily hemodialysis. Rather, it was designed (and originally launched) first for continuous hemofiltration of acute renal failure patients in the ICU and later for daily home hemofiltration for chronic kidney failure patients. Hemodialysis and hemofiltration are very different. With hemodialysis, the nitrogen-containing waste products in the blood are removed primarily by diffusion, a process by which mostly small molecules “vibrate” their way through the dialyzer membrane from the side of high concentration (blood) to the side of low concentration (dialysate). With this process, the larger the molecule, the less likely it is to find its way through the membrane and less of it is removed. Consequently, pure hemodialysis has fairly poor removal of middle and large toxins. One of these is beta 2 microglobulin which is the culprit behind carpal tunnel syndrome (amyloidosis).
With hemofiltration, on the other hand, the toxins are “dragged” through the membrane with the water that is squeezed out of the blood under pressure. In this process, there is no diffusion because there is no dialysate being pumped through the dialyzer. Consequently, there is poorer removal of small molecule toxins such as urea and creatinine. In order to get adequate dialysis with hemofiltration, a large volume of water has to be removed from the blood in each session; much more than could be physiologically tolerated. Therefore, injectable quality replacement solution has to be continuously infused directly into the blood stream to keep the patient’s blood volume at normal levels.
In order to establish what volume of replacement solution would translate into adequate therapy on a daily basis, NxStage commissioned a theoretical analysis publication by some well known research nephrologists which concluded that 18 liters of replacement solution would be required for an average-sized person. They reasoned that this amount of hemofiltration on a six day per week schedule would provide about the same small molecule removal as three-day-per-week hemodialysis but better middle and large molecule removal. They also stated that daily hemofiltration would result in far less small molecule removal compared to daily hemodialysis and still less middle and large molecule removal compared to nocturnal hemodialysis. They also stated that accomplishing this amount of water removal in a short (2.5 – 3 hour) session would necessitate a blood flow rate of 500 ml/minute. The premise of NxStage’s marketing of daily hemofiltration was that the larger molecules were of greater clinical importance than the smaller ones and that having this component of large molecule removal more than made up for any shortfall in small molecule removal.
Performing this kind of treatment means that 100 ml/minute of replacement solution from bags would be required to be infused into a patient’s bloodstream continuously over a three hour treatment. That’s 1500 ml every 15 minutes which makes the PHD’s backflushes of 200 ml every 15 minutes look quite small in comparison. I guess Debbie should be glad that NxStage’s plans to commercialize daily hemofiltration were derailed when the FDA required their product to be recalled about six weeks after initiation of their clinical trial. If her cardiovascular system gets worn out with 200 ml every 15 minutes, she would have had great difficulty with daily hemofiltration.
She won’t have to worry about that, however. Although they had contacted every company that produces sterile solutions in flexible containers, NxStage was never able to convince one of them to make hemofiltration replacement solution for them. Since they had already committed lots of money to developing their hardware, they had to resort to hiring local pharmacists make up the replacement solution from where it was sent to the home patients participating in the clinical trial. It did not take long for serious bloodstream infections to occur since it is nearly impossible for a pharmacist to produce that volume of solution and assure complete sterility. This lead to the recall.
In order to salvage the company, NxStage hatched a strategy to market their device for daily hemodialysis instead of daily hemofiltration. Hemodialysis requires no sterile replacement solution and the dialysate doesn’t even need to be sterile. The problem with that strategy is that you need a lot more than 15-18 liters of hemodialysate in order to achieve even the minimum standards for adequate dialysis. By comparison, the PHD provides 53 liters of dialysate every day and can achieve a weekly standard Kt/V of 2.1 on patients weighing up to 275 pounds in three hours six days per week. The NxStage System One on the other hand can not achieve this same target with the same regimen using 15 liters of dialysate per day on anybody weighing more than 132 pounds. If you elevate the amount of dialysate to 20 liters per day, then the upper weight limit becomes 165 pounds.
I don’t know how much Debbie weighs, but if a 155 pound man were to convert from a PHD to a NxStage System One, and his daily intake of protein of 1.1grams/Kg body weight did not change, his average weekly BUN would rise from 44 milligrams per 100ml to 66 milligrams per 100 ml or 50% higher.
What is more likely to happen is the same thing that happened in the late 70’s with a modality called Intermittent Peritoneal Dialysis. This modality provided insufficient dialysis meaning insufficient removal of nitrogen from the blood. When the physicians examined these patients’ BUN (blood urea nitrogen) levels every month, the values seemed in a reasonable range. What was actually occurring, however, was not that the dialysis was adequate, rather the patients subconsciously self-regulated their BUN by reducing the amount of protein they were eating. In other words, the excess nitrogen in the blood signaled the brain to reduce the patients’ appetite for protein. The result was an alarmingly high mortality rate in these patients due to malnutrition.
Computer models tell us that if that same 155 pound patient switched from PHD to NxStage but his BUN stayed the same, his daily protein intake would have to fall by 40%. Since chronic malnutrition is one of the strongest predictors of mortality in kidney failure patients, this is an issue to be taken very seriously.
Of course, under-dialysis and malnutrition can be avoided by simply increasing the volume of dialysate that is consumed on a daily basis. This however, presents a different problem to NxStage and their patients. NxStage acquires their dialysate from Germany and due to the fact that water is very heavy and shipping costs are based on weight, their shipping costs are such that they have no possibility of making a profit even when only 15 liters per day is used. I know this from some previous experiences at yet a couple of other dialysis companies in the peritoneal dialysis business. For those companies, shipping costs were by far and away the major cost component of providing peritoneal dialysis supplies and they were only shipping 8 liters per day per patient. Not only is NxStage shipping more than twice that amount, they also have a dialyzer and a blood tubing cassette plus ancillaries to include.
So, to MMiller who admonished us to be concerned about Aksys’ financial health, I suggest that the bigger concern by far is for NxStage. Last time I looked, Aksys still had something like $30 million in the bank and is already a public company making raising more money easier. Acquaintances of mine who have left NxStage (which is financed privately) assure me that their nest egg compared to their burn rate leaves them in no better condition.
So how, you ask, does NxStage propose to stay in business? Why make the dialysate in the patients’ homes of course just like all the other home hemodialysis machines do. They have already applied for and received clearance from the FDA for their “Dialysate Preparation Module”. Here is the link to the actual application and response from the FDA: http://www.fda.gov/cdrh/pdf4/K043436.pdf
This device will require the same things as all of the rest of the dialysis machines do, e.g.:
Plumbing and electrical modifications to the home
Water pre-treatment filters and carbon canisters
A reverse osmosis membrane
Dialysate concentrates
Pumps, valves, heaters, sensors, etc.
A separate cleaning and disinfection regimen.
Dialysate made by this machine will then be fed up to the dialyzer on the current System One module.
Because using this dialysate prep module is the only way they can be profitable, it is likely that they will price the bags in such a way as to make their routine daily home use too expensive for the clinics to earn a profit on your treatment. This, in turn, will likely force the clinics to insist that the NxStage patients use the dialysate prep module in their homes and only use bags when they are traveling and even then, the clinics may require the patients to pay for the extra cost.
From the patients’ standpoint, the use of 25-30 liters of dialysate per day in bags has much different concerns. These solutions are stored in polyvinylchloride (PVC) bags. In order to make these bags flexible, the use of platicizers is required and the most common one is called DEHP. This is broken down into MEHP by the body which is more toxic than DEHP. There are also other chemicals used in the manufacturing process. To my knowledge, daily use of this much dialysate in PVC bags every week for the rest of one’s life is unprecedented and the consequences of infusing this much DEHP would bother me. That may be why we are hearing reports of patients having a funny taste in their mouths after dialyzing on this system.
However, the biggest long-term problem that all patients face in doing daily hemodialysis is chronic inflammation. Over the past 10-15 years more and more clinical evidence is being presented in the nephrology journals that this may be the biggest problem to be managed in all dialysis patients because chronic inflammation in turn leads to the two biggest contributors of mortality in this patient population; hardening of the arteries (atherosclerosis) and malnutrition. Furthermore, chronic inflammation also is likely the primary culprit causing amyloidosis which is like having carpal tunnel syndrome in most of your joints and is a disease that shows up slowly after 8-12 years on dialysis. You all may find the most recent issue of Newsweek very interesting in this regard since it has a major story on how inflammation is now being discovered to be a major cause or contributor to many of our most common health care problems. Here is a link to the article: http://www.msnbc.msn.com/id/8271053/site/newsweek/
Chronic inflammation in dialysis patients results from three things: being more uremic than less (i.e. being inadequately dialyzed), having your blood exposed to the foreign surfaces of the blood tubing and dialyzer, and having your blood exposed to dialysate that contains endotoxin, a byproduct of dead bacteria (which it is allowed to contain according to the American National Standard for dialysate purity).
The bottom line is, the higher your state of chronic inflammation, the sooner you will get amyloidosis, the less you will eat, the more muscle wasting you will experience and the sooner calcium deposits in your arteries will lead to a heart attack.
So, how do you lower your state of inflammation? First, use the highest purity of dialysate. The dialysate normally used in dialysis clinics is pretty “dirty” and has been shown to be a significant contributor to inflammation. However, it can be made “ultrapure” by passing it through a final filter called an ultrafilter just before it enters the dialyzer. Most clinics don’t do this because it adds extra cost to each treatment. However, they might consider it for a home patient since there are not many such patients and the cumulative costs would be more tolerable. The Aksys PHD actually makes dialysate that is twice as pure as ultrapure. It falls into a different category called “injectable quality” which means that it can be infused directly into your blood. It is the only machine in the U.S. that has been cleared by the FDA to do so. This is why the PHD can automatically prime the blood circuit, give you fluid during a treatment without using a bag of saline, and rinse your blood back while you just sit and watch. This also means that it is also the least likely to stimulate inflammation.
The second key to reducing your level of inflammation is not to expose your blood to the foreign surfaces of the blood tubing sets and the dialyzer membrane. This may sound impossible and still dialyze but actually it is not. During the first several minutes of dialysis when your blood is flowing through a brand new dialyzer and tubing sets, there is an immediate and strong inflammatory and immune system response in your body. After about 20 minutes, this reaction subsides for two reasons. One is that your body starts to send out down-regulating molecular signals that subdue the acute inflammatory response but the other is that your blood leaves behind a coating on these surfaces of its own protein/fat/carbohydrates that insulates it from further inflammatory stimulating effects.
When a new dialyzer and tubing set is used with each dialysis, the inflammatory cascade is triggered all over again. Doubling treatment frequency from three to six per week would obviously then result in doubling the inflammatory insult that daily hemodialysis patients suffer; unless you use the same blood circuit over and over and disinfect it in such a way that the protective coating is preserved. This is exactly what the Aksys PHD system does. It uses only hot water for disinfection and avoids the use of any chemicals such as bleach or peracetic acid which strip away this protective coating. Preserving this coating, along with the injectable quality dialysate, result in this machine providing the world’s most biocompatible dialysis. The ramification is that the machine is much more complex than most resulting in more service calls, and it is obviously not portable, but patients who use it for the rest of their lives can count on living longer with better nutrition, less atherosclerosis, and amyloidosis. It comes down to a trade off between short term convenience and the possibility of traveling with a device, versus long term health consequences.
This brings me full circle back to the topic of backflushes. Since Aksys wanted to preserve this protective coating, they also had to ensure that the coating did not clog the dialyzer’s membrane and reduce its ability to transport the toxic molecules out of the blood. The primary reason for the backflushes, therefore, is to keep the dialyzer operating at near its original state. By backflushing the membrane, the pores in the membrane are periodically cleaned out but the coating on the inner surface of the membrane is left intact; pretty clever. In practice, it appears to work very well since the urea clearance for most patients stays near normal throughout a full month’s worth of uses. The side benefit is that diluting the blood periodically has long been used as a method of minimizing the need for heparin.
I am surprised that it never occurred to Debby that she could completely turn off the backflushes. I wouldn’t, however, advise doing this unless your physician really thinks it’s causing a clinical problem. Not only will your dialyzer clearance suffer, but you won’t be taking advantage of the fact that every backflush is actually an instance of push-pull hemodiafiltration which will contribute to the removal of middle and large molecules such as beta 2 microglobulin. In fact, maximizing the backflushes, especially over an eight hour nocturnal procedure, would result in very significant middle/large molecule removal; about 50% more than NxStage would have achieved had they been able to market the daily hemofiltration modality but without giving up the small molecule removal since hemodialysis will be occurring simultaneously. I wouldn’t be surprised if Aksys doesn’t eventually begin seriously pushing this modality since they would be able to tout all of the advantages of middle molecule removal that NxStage originally based their sales pitch on. It doesn’t appear that NxStage will ever be able to get back to the hemofiltration technique since, even with their dialysate prep module, they will not be able to infuse the solution in a patient’s blood.
Of course there is a major additional benefit to automatically reusing the whole blood circuit for a month; the patients don’t have to tear down and replace the entire blood circuit with each and every treatment. Not only does that save them significant time and effort but it reduces the amount of supplies that they need to store in their homes and also significantly reduces the amount of garbage that is generated every week.
I understand that each individual is motivated by different things but as a nurse, I am often dismayed and frustrated by decisions made by patients that are motivated by short term convenience when I know that there will be long term negative clinical consequences. That is why I felt compelled to share what I have learned about the respective consequences of each of these systems since I didn’t see anyone else discussing them.
It looks from your most recent message that this may be a little late but I hope you will give it some consideration. I sincerely hope this helps.
