Vascular Disease Management Interviews Stephen R. Ash, MD, FACP

Please provide a brief overview of the history of kidney dialysis, particularly as it relates to vascular access techniques and management.

The concept of dialysis dates back to the start of the 20th century. It was known that you could pass blood with various chemical impurities in it, which are the type that occur with kidney disease, through cellophane membranes with a salt solution on the outside, and some of the poisons of kidney failure would pass through. Those experiments were successfully done using blood in animal kidney failure. However, the real implementation of dialysis, like a lot of new concepts, awaited a solution to various technical limitations. Membranes needed to be improved and become more efficient and less prone to leakage; an appropriate anticoagulant was needed; blood pumps that could be used with sterile tubing were needed; and finally, long-term blood access was needed that would allow a very high flow rate, as occurs in the kidneys. Thus, dialysis was limited in the latter half of the 20th century by blood-access issues. During World War II, physicians actually had to sew catheters into the arteries and veins; it wasn’t even possible to think of hooking a patient up to an artificial kidney for several months until Scribner developed a shunt that could be sewn into the artery and vein in the forearm and left there. The development of fistulas, finally, was a concept that allowed a clinician with reasonable skills to place a couple of needles for dialysis that would be implemented for months to years. For patients in whom fistulas did not work, grafts were developed. Around 1990, chronic dialysis central venous catheters were introduced. These were dual-lumen catheters cut with a cuff to make them permanently tunneled, allowing for 400 ml per minute of blood flow. We still have those latter options today, which have been improved and still mesh reasonably well. Fortunately, catheters can be placed and used for access the day a patient needs his first dialysis treatment. They can last months while the patient attempts to build a fistula, which is probably a safer, albeit more difficult access.

What can you tell us about your work with sorbent-based dialysis solutions? What is the state-of-the art of this technology?

One of the major problems of dialysis therapy, besides access, is the complexity and the relatively high incidence of side effects and other problems. This has limited dialysis mainly to an in-center therapy as opposed to a home therapy. One of the problems with this therapy is that large amounts of purified, very clean water — approximately 150 liters — are required. This water must be freed of all soluble components that are normally found in drinking water. It also must have the right temperature, the right salt concentration, the right conductivity, and so on. Much of the difficulty in implementing dialysis in the home has been to provide access to this type of water. Some measures have been taken to improve this situation such as supplying 5-liter bags of sterile fluid to the home, but these are not perfect solutions. The beauty of sorbents is that they are compounds that can bind other chemicals and compounds. I have always been fascinated by the success of the sorbent column — a simple collection of inorganics and a small amount of urease, which bind all of the kidney-failure toxins, while at the same time producing or allowing to pass all of the good stuff. The sorbent column was actually first implemented in-hospital for acute dialysis over 30 years ago and was then used extensively in-home. I became interested in the possibility of sorbent use in a simplified night-time home dialysis setting in the 1980s. I formed a company called Ash Medical in partnership with a very skilled local businessman, Bob Truitt. Ash Medical created a home dialysis system using a sorbent column and featured only one needle, which would pull blood out and put it back in. This machine was reasonably successful, but the home dialysis market sort of disappeared around that time and reemerged around the year 2000. Bob Truitt and I then formed a subsidiary of that original company called Renal Solutions. Our new subsidiary was given the task of bringing sorbent therapy back to market with more modern equipment. The project was successful and the device was FDA-approved, and that company was “absorbed” by a company called Fresenius Medical Care. They are still working to finalize the concept and versions of that part of the machine that will go to market. In the long run, the beauty of sorbents is that you can use 6 liters of tap water, pour it into the machine, push a button, and end up with nearly sterile, very pure dialysate and the ability to run that dialysate at very high levels, such that 6 liters have the same chemical effect as about 100 liters of purified water in a standard dialysis machine. Other groups are also working on this technology. If carried one step further, instead of the patient walking around with 30 to 40 liters of fluid during dialysis, sorbents chemicals would only weigh 1 lb. They can regenerate the dialysate that would be needed for a portable artificial kidney. Sorbents are somewhat more complex chemically to implement than standard dialysate, but in terms of physical implementation and physical steps to bring dialysis into the home or an alternate care market, they have tremendous potential. Research is currently underway on oral sorbents to remove potassium, urea, ammonia and so on. This may help patients with chronic kidney disease even before they go on to dialysis treatment.

What types of projects are you currently working on?

My own research efforts occur within several companies. The R&D operation for Renal Solutions, developer of home-based dialysis systems, is located in Lafayette, Indiana. HemoCleanse, another company, offers an artificial liver application; ZS Pharma has developed a pill that can be taken for various toxins; and Ash Access has done research leading to the development of new catheters and a catheter lock solution, which when put into a central venous catheter, greatly reduces the risk of infection and clotting. Zuragen™ is a unique combination of the antiseptic chemicals citrate, methylene blue and parabens. Citrate is used for anticoagulation of the catheter. Methylene blue is a weak antiseptic that is given intravenously in large doses to many patients. Parabens are preservatives that are frequently used in saline and heparin. Their combination of these three agents, we discovered, is tremendously synergistic in killing bacteria. We just completed a clinical trial which showed that using that particular mixture of compounds instead of heparin resulted in a 70% decrease in the incidence of catheter-related blood stream infection in patients with catheters used for long-term dialysis. This is a different direction than many might think to take for an antibacterial catheter lock — most would assume that an anticoagulant would be combined with an antibiotic, but it is very important these days not to use antibiotics for prophylaxis of infection because of the risk of resistant organisms. In Zuragen™, we have compounds for which there is virtually no developing resistance, are highly effective in killing bacteria and fungi and appear to be very safe, even when given intravenously. This represents a major project for Ash Access. Ash Access has also continued our work on improving central venous catheters for dialysis, the most recent improvement leading to the Centros™ catheter.

Tell us about the split-tip Centros™ Catheter and how it can improve dialysis efficacy and quality of life for patients.

As I mentioned, the success of dialysis therapy depends on how well the access works. With regard to central venous catheters, we think that an antiseptic catheter lock can greatly diminish infection. The other major problem vexing the use of chronic hemodialysis catheters placed in the central venous system is that over time, they tend to lose flow. They usually flow well the first day, but a week later, the flow may be less, and a month later, not only will the flow be less, but some days it may not work at all and enzymes may need to be added to get rid of clots. Over the long term, sometimes that doesn’t even work, and the catheter needs to be replaced. This loss of flow is principally due to sheathing, which is fibrous tissue that develops around the catheter and tends to develop wherever the catheter touches a blood vessel. When this sheath reaches the tip of the catheter, flow diminishes and clots form over the tip. There was some very good work done in a pig model about ten years ago by Dr. Ted Kohler in Vascular Surgery at the University of Washington, which showed that if a catheter is supported in the middle of the vena cava, it will not develop sheathing, since it is held away from the vein wall. Sheathing is actually the growth of a new blood vessel surface which requires vascularity from the vessel wall as well as growth hormones, white cells, fibroblasts, epithelial cells, etc., such that it incorporates the catheter into a structure that resembles the vein wall. If contact with the wall can be avoided, then sheathing will not occur. With the Centros catheter, we developed a tip featuring two curves, outward and inward, so that the blood access ports are held in the center of the vein, and there are only two contact points at the lower part of the superior vena cava. Thus, a sheath may develop at the upper part of the jugular vein where the catheter enters the vein, but it does not continue down to reach the tip and stop the flow. The Centros™ catheter was successful in the first limited clinical trials and in the first catheters of this type that were used, and it certainly makes sense that if you can keep the catheter tips in the middle of a flowing vein instead of touching the vein wall, then the catheter will remain much more open and free. A few other changes in the catheter have also been made: there are no side holes around the tip so that all the flow goes in and out of the tip. The side holes were removed primarily to prevent blood from flowing into the tip of the catheter between uses, thus maintaining the anticoagulant better within the catheter and helping to maintain patency. The major goal of the Centros™ catheter was to solve the problem of sheathing and covering the surfaces of the catheter down to the tip and blood entry port — problems that had not yet been addressed by any other dialysis catheter. Our goal is to have dialysis catheters that are flowing as well six months after they were placed as they did on day one. We expect to prove this via clinical trials and market feedback. These improvements are needed because even in studies where every care was taken to prevent infection and there was optimal use and locking of the catheters, over 50% of the catheters have ceased proper functioning by nine months. I am hopeful that our catheters will function twice that well — that more than 50% will still be functioning well at one year and perhaps even longer. If the Centros™ catheter’s design solves the problems of flow, and if antibacterial catheter locks can diminish infections, then it would be possible to have long-term use of central venous catheters for dialysis. Paradoxically, there have been some types of catheters used in some hemodialysis patients that have lasted five years. No one would suggest that a catheter is safer than a fistula, but there are patients, especially home patients in Italy, for example, who took very good care of their catheters, and with a little radiologic help, almost all of the catheters functioned five years later. However, most catheters today still need frequent replacement — and the more often catheters are replaced, the more tracks are formed in the vena cava and the more often other sites must be used for placement. Besides diminishing sheathing around the catheter, we hope that the Centros catheter’s design will minimize stenosis in the superior vena cava. About one out of ten patients with chronic central venous catheters for dialysis develops a clinically severe stenosis in the superior vena cava due to irritation of the vena cava wall by the catheter. Many of the catheters placed today have the tips going down into the heart. With the Centros, the tips do not have to enter the heart — and in fact should not enter the heart; there are only two very small points of contact in the superior vena cava instead of a long line of contact with the solid-body catheter. No long-term data are available yet for the Centros catheter, but the experiments Dr. Kohler conducted were very encouraging; there was much more stenosis and fibrosis in the animals that had a standard catheter versus his ringed catheter.

What are some of the techniques and complications involved with tunneled hemodialysis catheters?

There are two basic methods for placing a central venous catheter for dialysis: using a split-sheath and over-the-wire. A small incision is made in the skin over the lower part of the jugular vein, then a guidewire, dilator and sheath are placed — if that is the chosen method. The catheter is then tunneled from the right shoulder towards that same incision and the tip is brought out and placed down into the sheath and into the vena cava. In over-the-wire placement the catheter is tunneled, the tract around the guidewire is dilated, and the catheter is threaded onto the guidewire and advanced into position in the superior vena cava. Fluoroscopic imaging helps accomplish this placement, as it allows visualization of the guidewire’s position and ensures that the tip of the catheter is where it should be. With current catheters, in fact, the function of the catheter is highly dependent on where the tip ends up. If the tip ends up in the superior vena cava, it will be laying against the vein wall, resulting in poor catheter flow. So the tip must be positioned in the middle of the right atrium to get the catheter to work at all. Unfortunately, the way the heart and lungs are positioned when the patient is lying down on the X-ray table differs from when the patient is seated in a dialysis chair, which causes quite a bit of change in the position of the catheter tip. Thus, the placement of the catheter tip requires a considerable amount of judgment, because even with fluoroscopic guidance, the physician must try to determine where the tip will lay when the patient sits up — whether it will pull back, in which case it should be placed further down, and so on. With the Centros™ catheter, we aim to eliminate most of that uncertainty since the catheter will work with the tip positioned anywhere in the lower third of the superior vena cava. A catheter can be placed in the right internal jugular vein, which is the optimal place. The catheter can also be placed in the left internal jugular vein, although at this site, the bends of the catheter push the catheter tip against the right side wall of the vena cava and right atrium. Left IJ catheters, therefore, have a higher failure rate early on and oftentimes do not work at all. If they do work, however, they can do so for a long time. Other sites for catheter placement are the external jugular vein, and if that does not work, the femoral vein is an option, but it is less successful over the long term. In the old days, dialysis catheters were actually placed by surgical cutdown of the jugular vein, with strings placed under the vein and the catheter inserted and tied in — which of course was very limiting! The Seldinger needle technique, therefore, represented a major advance. In terms of complications, approximately two-thirds of the catheters are lost to infection, which relates to how much contamination there is of the lumens and connectors. When utmost care in catheter connection is used, infection rates can be minimized. The nurse and patient should wear masks, gloves should be worn by the nurse, and the connectors should be soaked in povidone-iodine or other disinfectant for five minutes before taking them off. The connection should be done as cleanly as possible. In spite of these types of precautions, the national average is about three infections per one-thousand patient days, which translates to about 9% of patients with infection in a unit every month. These infections can be very devastating, as the patients not only have fever and low blood pressure, but they can develop much more serious infections of the heart, bones, blood, and so forth. These patients often require hospitalization as well as removal of the catheter and placement of a new one. Some catheters can be salvaged with antibiotic locks. Good centers can reduce that infection rate to about one per one-thousand patient days, which is very encouraging, but that is still about 3% per month, or one out of thirty patients. But even if the infection rate is minimized in some patients — and by the way, home patients tend to do very well in terms of avoiding infection — the problem of reduced flow rate may still occur, and after one or two months, enzymes are added to try to open up the catheter. When the catheter fails, a new catheter must be placed through the same site or a different site. X-rays taken through the catheter tract usually indicate sheathing of the old catheter site.

What role does stenting play in treating vascular access dysfunction?

First of all, approximately one out of ten patients with central venous catheters will develop a significant stenosis in the lower vena cava. Blockages can also occur in the subclavian vein area due to the catheter’s placement or sometimes due to a smaller catheter’s placement in the subclavian vein. In the superior vena cava, stenting is very much the last resort, because not only is it difficult to do, it is somewhat risky as well, since appropriate-sized stents are often not available and most are not approved for central venous use anyway. Many times, stenoses occur in the innominate vein and stenting has been fairly successful in this area. Unfortunately, catheters are usually the culprit in these types of stenoses. We therefore try to avoid placing central venous catheters through veins on the same side as an existing or planned fistula. When a stenosis occurs in the subclavian or innominate vein, and a fistula is then placed, that same vein will have three or four times the normal blood flow, often resulting in swelling of the arm due to the stenosis. Before making a fistula, the status of the central vein must be checked in patients who have had a catheter. In terms of the access work related to fistulas and grafts, stenting has shown some definite benefits, but it also has some limitations. Some stenoses within a fistula cannot be opened with angioplasty in a permanent way, and therefore, placing a stent there will help. More importantly, veins going from the fistula section up towards the chest, and the basilic and cephalic veins have benefitted from stenting. The downside of stents within a fistula is that wherever a stent has been placed, except through a stent, needles cannot be introduced as easily, so the X-ray images may be beautiful, but there is nowhere to place the needle in a completely stented fistula. Some practitioners place needles through covered stents, but the outcomes are still less than optimal. Thus, many accesses can be saved with stenting, particularly with stenoses in the upper arm veins, and less frequently in the central and innominate veins, but stenting is definitely the last resort for vena caval use. It is much more important to try to minimize stenosis in the these veins. One way to ensure that is to have the first catheter work for a long time, and another way is to avoid causing irritation in the lower third of the superior vena cava.

What are your thoughts on renal artery angioplasty and stenting versus medical therapy for renal artery stenosis treatment?

I don’t consider myself an expert in this area, but I am a practicing nephrologist here in Lafayette, Indiana, with a very large medical group. Thus, we do see patients for whom stenting of the renal arteries is considered. A large, prospectively randomized study conducted recently showed that renal artery stenting did not preserve kidney function nor have a long-term beneficial effect on hypertension. Every practicing nephrologist has come across patients in whom the progression of kidney disease is so clear and the cause so obviously due to renal artery stenosis that it is very difficult not to try stenting — and we have found that stenting failed in some patients, while in others, it was truly the turning point in their disease course. Thus, on an average scale, especially in trials with somewhat modest inclusion criteria, stenting has not proven to have a demonstrably significant effect. However, if used judiciously and in patients in whom the course of renal disease is clear, stenting can be beneficial. I think that renal artery stenting may be somewhat overused, but it is not going away and can be a valuable tool when used in the right patients.

What proportion of today’s permanent hemodialysis operations are autogenous AV fistulas versus prosthetic AV grafts and catheters?

The CMS (Centers for Medicare and Medicaid Services) and the NKF (National Kidney Foundation) have developed a program called “Fistula First” to improve the percentage of fistulas used in the United States. By all measures, this program has been successful, but a difficult concept to sell. It requires getting practitioners who are used to doing the easy and practical thing such as putting in a graft or catheter to switch to something that is considerably more difficult in many patients, creating an AV fistula. Today in the U.S., approximately 54% of all patients have fistulas as their chronic access, which represents a slow but linear increase in the past ten years. Use of grafts, however, has fallen from 40% to about 20% today. The percentage of patients with catheters used at any one time has remained the same, especially because fistulas have not been able to be created in many patients before they begin dialysis. Eighty-two percent of patients begin dialysis without a suitable graft or fistula formed and must have a tunneled dialysis catheter placed. Incidentally, it is definitely better to have that patient — even if hospitalized — receive a tunneled catheter from the very beginning rather than an acute catheter, which has more negatives than a chronic catheter and none of the positives. According to USRDS data for 2010, the prevalence rate in the U.S. is about 54% for fistulas, 20% for grafts and 26% for catheters.

Has the U.S. caught up to Europe in recent years with regard to the use of native AVD fistulas for dialysis access?

Europe generally does a better job of creating fistulas early on in patients. Approximately 80% of patients in Europe have fistulas, 10% have catheters and 10% have grafts. It is important to note that there is an older dialysis patient population in the U.S. Dr. Mark Glickman and his group in Virginia recently published a paper evaluating the success of implementing fistulous grafts and catheter use in patients > 70 years of age. They found that the success of fistulas in that age group is much lower than the average. The primary failure rate of fistulas in all patients is about 30%, but the failure rate of a fistula in a patient > 70 years old is 65%. Thus, two or three attempts often need to be made to get a fistula started in this older patient population. The Europeans are somewhat better at getting fistulas started and identifying patients early; they also have more nephrology input in the fistula planning process. In fact, in Italy and Germany, a large number of nephrologists still place their own fistulas. Also, the Europeans tend to look at grafts as the last resort. In Glickman’s paper, grafts and catheters performed much better in elderly patients, with early functionality at nearly 100%. Some practitioners have said that they would rather have one good graft than three failed fistulas — and they may be right. The Europeans, thanks to the interest of nephrologists like Klaus, Conner of Cologne and others, have become very creative in how they make fistulas — mid-arm fistulas, median antebrachial veins rather than the standard cephalic, even basilic veins, some transpositions, etc. The U.S. is making progress with the “Fistula First” goal, which aims to achieve a rate of > 65% fistulas within a couple more years. However, there are significant costs in terms of surgery, radiology procedures, follow-up, vein mapping, and so on.

Where do you see vascular access techniques and technology headed in the next decade or so? Will patients with acute kidney disease live longer?

First of all, we need to evaluate each of these available access devices and determine how they can be improved. Most recognize that a well-functioning fistula offers a very safe, long-term access, though it may not be the easiest in terms of needle cannulation or use. One development that seems fairly simple and potentially very helpful is the concept of using a small catheter to create a track into the fistula for about ten days and then following that catheter track with a blunt needle called a “button hole”. The “ClampCath” was first tested at St. Michael’s Hospital in Canada with publication about two years ago and is now beginning to grow across the U.S. Once the fistula needs to be accessed, instead of sticking it with a brand-new sharp needle in the first four to five dialysis sessions, this plastic catheter is inserted and taped in the arm and after removal of the catheter ten days later, a fairly good track has been formed to allow for the introduction of a blunt needle into the fistula. The use of button-hole fistulas has considerably prolonged fistula life in many patients since the same site is being entered, and there is no need to cut a new hole in the vein each treatment. The alternative is hundreds or thousands of needle-sticks in a couple of inches of vein, which tends to result in leakage in the vein wall, aneurysm formation, clotting and swelling. If an antibacterial catheter lock ended up cutting infections by 70% and and a new catheter designed provided flow rates of 400 ml/minute for months or years — catheters would be a much more practical option for those patients in whom other types of access are not possible. Some improvements have been made in the area of grafts such as reinforced Dacron grafts, a tapered approach to the vein wall, and the ability to stick the graft early. Also, a new graft-cath device called the Hero is very clever and will probably have a place in the market, but it has some of the same disadvantages of catheters and grafts. I think that an entirely new fourth alternative is needed in order to truly respond to the needs of dialysis patients. One idea is to replicate the way mother nature makes connections in arteries and veins. We should also test new locations for access, etc. Fistulas were first created about 40 years ago, grafts 30 years ago and catheters have been used for about 20 years, but a fourth option still eludes us.

Which medical specialties are involved in the treatment and management of your patients? Is greater collaboration needed?

It is becoming increasingly clear that the success and health of our patients do not just depend on the dialysis procedure. All nephrologists realize that the more continuity, cohesiveness and attention that can be built in to the care of their patients who have comorbidities, the better they will do. Sometimes the nephrologist takes on the role of primary physician by default, which then requires management of the patient’s other comorbid conditions such as heart disease, diabetes, peripheral vascular disease, vascular access maintenance, and so forth. There are occasionally skilled internists or primary physicians who stay involved with the patient, which is ideal. A host of other specialties are often involved in treating the concomitant diseases of these patients. Interventional radiology and nephrology are very important specialties for dialysis patients. Many physicians within the nephrology specialty have learned the various interventional techniques for graft and fistula maintenance. In fact, a dialysis patient with a graft or fistula will undergo, on average, at least one maintenance procedure per year. Stenoses, thromboses and aneurysms can develop, and if not diagnosed in a timely manner by careful physical examination and treated immediately in the interventional suite, the problem can become more serious. Aside from nephrologists, interventional radiologists and internists, these patients will likely also need the care of cardiologists, vascular surgeons, endocrinologists, infectious disease specialists and mental health professionals.

You first earned a degree in physics. What then inspired you to pursue a medical degree and how did you decide to pursue nephrology as a specialty?

I was always very interested in science and the more complex and challenging, the better. On the other hand, I was also drawn to working with people. Although I loved physics, one of the reasons I decided to pursue medicine is that I wanted the opportunity to support people in need. And the second reason, which was more obvious to me, was that, quite frankly, I did not see myself making any major contributions in the field of high-energy physics! Instead, I was attracted to the challenge of applying basic science principles to solve questions that arise in physiology, anatomy and surgery. I needed to scramble when I was a Physics major at Northwestern in order to complete the requirements for medical school. I have found the practice of medicine to be rewarding both intellectually and emotionally. Dialysis is a very rewarding practice because it is not often in medicine that you see patients suffering from a serious acute or chronic disease improve greatly with the use of a machine — not just acutely, but over the long term as well. Mortality in dialysis patients is not so much dependent on the artificial kidney or the efficacy of the dialysis as it is on how well we manag comorbid conditions of the patient. It is quite rewarding to be able to buy even a few years of life for a patient and improve his quality of life. My interest in nephrology in particular stems from two things. When I was in medical school, I was absolutely fascinated by regeneration — the ability of the kidney to heal itself. I was conducting basic science research in regeneration of kidneys following acute kidney injury and I published a couple of papers on the topic. My life changed the first time I saw an artificial kidney. Here was a simple collection of cellophane, roller pumps, salt, water and a heater that worked to remove toxins and bring patients out of uremic coma. It amazed me for two reasons: first, it replaced such an incredibly complex organ with fairly simple components, and second, I found the artificial kidney machine to be amazingly crude and was interested in contributing to its improvement. I thought that with the right concept, the artificial kidney could be made more practical, easier to implement and less cumbersome. As a medical resident, I learned how effective sorbent chemicals were at removing toxins and how they do so in a much more sophisticated manner than just passing a dialysate of water and salt. I find the nephrology field ideal because I like people, machines and the scientific discipline it takes not only to properly design a device, but to test it clinically as well.

How do you divide your time between patient care and product research and development?

I came to Lafayette in 1975 before which time there were no dialysis centers in the state of Indiana. I joined the Arnett Clinic, a 40-person multispecialty group, which has grown to 200 physicians and nurse practitioners today as Clarian Arnett Health. There are now dialysis centers located in all of the surrounding towns, two of which are here in Lafayette, and two home programs as well. When I joined the Arnett Clinic in Lafayette, they agreed to let me spend half of my time in clinical practice and half of my time doing device research. My goal was to work on a portable artificial kidney, new types of blood access, applications in liver failure, etc. This time ratio can vary from 60%/40% or 70%/30% some weeks, depending upon how heavy my clinical workload is. I have established a wonderfully skilled team of researchers. Dave Carr, a biochemical engineer, has been with me for twenty-five years. A biochemist Janusz Steczko, has been with me for ten years, and Tom Sullivan, an electrical engineer, has worked with me for eight years. This team allows for the proper amplification of my skills and they are able to manage projects on their own, which keeps the research on a steady keel and frees up my time for clinical work. Our nephrology department is wonderfully supportive, with Dr. Jim Sutton and Dr. Akram Al-Makki, Amy Allspaw, CNS, and a group of excellent nurses. In terms of device development, collaboration is crucial. Purdue University, here in West Lafayette, is an excellent research partner and conducts all of our animal trials. We go through their animal care and use committee, and they are very skilled at conducting trials with minimal discomfort to the animals. The key to device innovation is to start with a plan, find the right mix of people to work with, identify the projects that are most needed and, more importantly, which ones are feasible. We have also done very well with N.I.H. funding, and the State of Indiana has been helpful as well. I have one long-term partner in Bob Truitt, our CEO, who has kept the whole operation together while we pursue these projects. When I am approached by other nephrologists and physicians who often have excellent ideas, I ask them, “How serious are you about this?” — because an enormous amount of work is required to move from concept, to benchtop work, to animal work, then pre-clinical testing, clinical trials, FDA approval, and then finally, finding the right marketing partner. AngioDynamics has been a great partner for the Centros catheter. This company is making a significant contribution to the field of vascular access.

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Dr. Stephen Ash can be reached at sash@ashaccess.com

Dr. Ash is a practicing Nephrologist at Clarian Arnett Health in Lafayette, Indiana and also Medical Director for Wellbound of Lafayette. He is past President of the American Society for Artificial Internal Organs and the American Society of Diagnostic and Interventional Nephrology and serves as Editor of the ASDIN section of Seminars in Dialysis. He is co-founder of several biomedical device and drug companies including Ash Access Technology, HemoCleanse, Renal Solutions, and ZSPharma. He holds numerous U.S. and worldwide patents and has published over 100 peer-reviewed articles. Dr. Ash is fortunate to have a caring and tolerant family of professionals. His wife Marianne is a veterinarian, his daughter Emily a physician, and daughter Sarah a lawyer.