ANNA 36th Annual National Symposium
Complications of Anemia and the CKD Patient
Part Two of Two
Treatment of anemia
How have we been treating anemia? If you look back, we started treating in the 1600s with animal blood. I am sure some of my husband's relatives have some bull in them some place. It was not until about 1901 that they started checking blood groups and then they finally discovered the Rh factor in about 1940s. In about 1945 is when the American Red Cross came into being so they could distribute blood. About 1990, the timeline says: blood substitutes, and then the EPO stimulating agents, as well as the new kid on the block, darbepoetin, in 2000.
Treatment options for anemia
The erythropoietin stimulating agents that we have are based on recombinant DNA. It is a technology that stimulates the production of red blood cells. We have epoetin alfa here in United States. There are other variations of epoetin that are available in other countries, and we also have darbepoetin alfa.
The other treatment for patients not on dialysis of course is transfusion. We mostly try to reserve that for patients who are severely anemic and for acute anemia, especially when you are dealing with patients with CKD. Lots of time you are dealing with extra volume, you have to think when you are giving extra volume to these patients, about how you may have to then diurese them. Another important piece is that, if you are dealing with a younger population, you want to limit the amount of transfusions that you are going to be giving, especially if they are going to be transplant candidates.
Maintaining iron stores
The other way of treating anemia focuses on iron stores. If you want to get a good response to the medications that you are using, I cannot stress this enough. People think that they are failing treatment because they are not getting the blood counts that they want or the response. Look at what you are doing in your iron management. There are newer forms of iron. They can be given in non-hospital settings. We most certainly do. We give iron infusions. There is iron sucrose and ferrous gluconate, and these can be given IV push.
Let's look at erythropoietin - the chain up there. This is erythropoietin alfa. There is also darbepoetin alfa which has two additional chains of carbohydrates. Because of the increased chains of carbohydrates, you go from a 40% to a 52% content in carbohydrates, and that gives you a different weight, and so darbepoetin is a heavier molecule, 30,000 (epoetin) to 38,000 (darbepoetin) daltons, and darbepoetin also has some changed amino acids.
What does that mean? If you look at the pharmacokinetics of epoetin vs. darbepoetin after an injection - and here you are looking at blood half-lives - you can see that darbepoetin stays around longer than epoetin alfa.
Increasing carbohydrate content
What does this mean? In animal models, as you increase the carbohydrate content, you also are able to increase the serum half-life, but there is some data that shows that EPO receptor binding affinity tends to decrease.
Studies comparing epoetin alfa and darbepoetin
This study compared epoetin alfa and darbepoetin. They brought the hemoglobins up into the 14 g/dL range and then withheld these medicines. After they withheld the medication, they watched to see how fast the hemoglobins would fall, until the hemoglobins got below 12. After stopping darbepoetin, the hemoglobin values fell at a faster rate; to reach the under 12 cutoff took about 7 weeks versus close to 9 weeks for epoetin alfa. There are studies that are still underway in this area, and we do not most certainly have the answers, and we do not know all the reasons why, but that is an important graph.
Indications for erythropoietin
When you look at the package insert you see that epoetin alfa is indicated for patients who are not on dialysis, as well as for patients with non-myeloid malignancy. It is indicated for dosing 3 times a week and then once a week afterwards.
Indications for darbepoetin
This is from the darbepoetin insert. Darbepoetin is indicated for patients not on dialysis and it can be given to patients once every two weeks. It is also indicated to treat anemia in patients who are being treated for cancer.
Once weekly epoetin alfa dosing
This is looking at once-a-week dosing of epoetin alfa. You can see that when the patients were being dosed once a week, their Hb went from baseline right up to a target of greater than 12 by using 10,000 units once a week.
Poster presentation summary
This is our poster presentation from several years ago, and I will show you what I have for update, but this is what we use for our dosing guideline in our clinic. We start the patients somewhere between 100 to 150 units/kg. If their hemoglobin is 11 to 12 g/dL, we then increase their dose of epoetin by 50% and dose every 2 weeks. Once patients are able to maintain that hemoglobin, we then go to every month dosing.
Epoetin dosing data
This is what our data was a few years ago. At the end, I will be showing you what our data looks like now. We have a large population of our patients who are dosed with epoetin every 4 weeks, and they are able to maintain a hemoglobin with an average dose of about 17,000 IU. We found that after 6 months, once patients have been treated with epoetin for greater than 6 months, 90% were able to be dosed less frequently than once a week, and more than 50% could be dosed every 4 weeks.
This was a study that looked at 97 patients and they looked at extending the dosing interval out to 4 weeks. The baseline hemoglobin was 10 to 12 g/dL in patients being treated every 2 weeks. So the patients had been established on dosing every 2 weeks. The creatinine clearance was between 15 and 40 ml/min. The investigators then doubled the epoetin dose and extended the treatment interval to once a month and watched the patients for 29 weeks. The result was, that they were able to maintain the patients with a hemoglobin of 10 to 12 for 79% of the cases. Only 82/97 patients completed the study, so that was 79% of 82, or 65 patients.
PROMPT Study: Objective
Here we are looking at the PROMPT study, which looked at extending dosing interval for epoetin alfa.
PROMPT Study: Methods
What they did was, patients were randomized, in an open label fashion. They were randomized to receive epoetin according to different treatment intervals and doses. The treating physicians were able to reduce the initial epoetin dose during follow-up, but they were not able to increase the dose. There were four dosing groups.
PROMPT Study: Randomization
Patients were randomized to either 10,000 of epoetin once a week, 20,000 every 2 weeks, 30,000 every 3 weeks, or 40,000 every 4 weeks. The patients were followed for 16 weeks.
PROMPT Study: Inclusion criteria
At entry, patients had already been treated with Procrits™ (epoetin alfa) for longer than 2 months.
PROMPT Study: Hb values
What this means is that if you looked at the once a week group and at their baseline and final hemoglobin levels they were able to accomplish that the same with the 2-weekers as well as the 4 weeks.
Midpoint summary: CKD and anemia
The summary, at the midpoint of my talk, and I am guarding you so you cannot leave, is that with anemia management in CKD patients, we can decrease cardiac damage. We can decrease the mortality and hospitalizations. We can improve patient symptoms. We also know that we are not meeting NKF K/DOQI targets.
Less frequent dosing
We also know that we can safely dose patients once a week, and there are studies suggesting that we can dose safely every 2 weeks, 3 weeks, and 4 weeks for both agents (epoetin and darbepoetin alfa).
CKD care plan
Back again to this comprehensive plan. We know that this is one of the keys, managing anemia. We know that we are not doing a good job.
What is the answer? You are. Nursing is the answer, folks. I know you are all nurses, but you know what, you could be the answer to all that is going on with CKD. We know there is an interest. You have been attending all the CKD programs. This is such a good fit for nursing. Develop an anemia management program. I am not asking you to going and change your career, but you must have some free time. As we go forward, I am going to show you how we put this piece together. If you can do the anemia piece, you could also do the CKD piece. If you cannot do either one of them, then there is plenty of work to do for community outreach. We have had some wonderful presenters in this symposium. We had a keynote speaker that talked about the passion of getting involved with things that mattered. We are nurses and this matters. This is such a good fit for everything that we do.
Gallup poll - how people see us
Why should we even get involved? This is a Gallup poll that was done this fall. They telephone interviewed over a 1000 adults, asking who are the most honest and ethical professional. Nurses are at the top! Not only are we at the top, but we have been at the top since 1999. We did lose 9/11 to firemen, but we have been at the top. Why is this important? It is because when you look at patients, we have patient trust.
Alleviating anemia symptoms
What other way do we get patient trust? When you start taking care of the symptoms of anemia, you become a god or a goddess, when the patients come in after they are feeling better. They are getting out. They are walking around. They are not taking naps. They are not sleeping. You see a lot of smiles on patients. In fact, Phyllis, one of my anemia nurses gets more candy on Christmas than I have ever seen in my whole life.
Why get nurses involved?
Why do you want to get involved? Because you have the opportunity. Become a nurse leader. You can be valuable to a Nephrology office. You can be valuable to patients. You can improve patient outcomes. You can implement new tools or education-type programs. You can create your own, make things your own. You have the ability to take all of this information that we have been learning about during this whole symposium about how to empower and motivate and educate patients.
How to start an anemia/CKD program
How can you even start? I have a few suggestions. You can go and approach a nephrologist if you have a good relationship with a nephrologist or a nephrology practice out there. I would suggest approaching somebody who has power within, especially if it is a large practice, but approach them and find out how are they caring for their anemic patients. Are they doing it in the office themselves or are they outsourcing?
A lot of nephrology practices send patients over to the hospital to get medications. Is the nephrology practice interested in starting an anemia/CKD program? Maybe they will be interested if you want to see how they are doing.
You can audit a few charts to see what some of the problems are within that practice; maybe they wait until the labs come back 3 months later, wherein they send a patient to the hospital, by then it is 2 months late. What are some of the issues about starting a program and how well are they doing? We have to audit a few charts and look at how well anemia is being cared for in the office.
Anemia / CKD team
How do you put a team together? If someone is interested, identify whom a core team might be composed of. It might be the nephrologist, it might be a nurse, if you have nurse practitioner in the practice or even the practice manager. You want to find out who is the leader. Once you start getting this together, you want to see who is going to be running the protocols. How are they going to be developed? There are some wonderful resources out there, whether from RPA or NKF, they all have a whole big book for CKD resource, and you can consult other programs. We have had multiple programs from across the country come and see how we are doing and how we put our program together. Then you can establish some of your guidelines or your protocols. You know what medicines you are going to be using, how you are going to be dosing, and how you are going to conduct your protocols, and maybe some CQI.
Effect of the team leader
The team is only effective as its leader. I put the leader there at the core because that is going to be the person who is going to keep the program together. Especially for nursing, many times when a program falls apart, it is because you have too many leaders. In fact, it reminds me of a good joke. What is the difference between a nun and a nurse? A nun only has to answer to one God. I have great relations with the doctors that I work with. I mean that you have to have support. You cannot run a program where different people are saying, "Well I don't why you dose this way? You should be doing it this way." It will pull a program apart if you get this sort of response. You have to identify the core that is going to help support you and the program.
The keys to a good leader are that they have to be creative, they have to be knowledgeable, they have to know what is going on out there, you have to know about some of your reimbursement issues, and you have to have the support as well as a way to bring the whole team together.
Medications: Cost issues
You might have to research what distributors are out there and some of the costs that are associated with your anemia meds, because somebody else in the program has chosen to buy a medication from x, y, and z, you have to resource, go and see what are some of your other options, because a source has been established before does not mean that they are the best company to go with.
You have to look at how you do contract purchasing, maybe volume or market share, and your billing. Look to see who is doing your billing. This is very important, because this is going to either make or break you. If this task has been outsourced to somebody, does the company that has been hired know to do this? Or if it is somebody in the office, do they have an idea of how to do the billing? They are They may not be checking out the things that you need to check, and then the next thing you know, you are losing money with these medications, and so that is truly the key. If you are going to put a program together, have a good relationship with your billing people because as you are implementing your program, you are going to want to go back and look and see how you are doing and what are the things that are falling through the cracks.
Patient education and empowerment
Patient education and empowerment, each patient carries his own doctor inside of him. They come to us not knowing that truth. We are at our best when we give the doctor who resides within each patient a chance to go to work. When you are building a program, that is an important part. If you are going to have someone coming into the office every week or every other week, they are going to want to feel like they are getting something out of your program.
This cartoon says, "Does it look like a happy chart to you?" It is not only very motivating, so you are going to think of ways of how are we going to motivate these patients?
This is an interesting study. It came out of Texas. What they looked up was that patients with bad heart disease. They did a PET scan in the very beginning to look at their blood flow and then they did it 30 months later, and they then did an analysis of how well those patients were doing. By the patients' motivation, they broke them into 3 groups. The patients who were highly motivated had a much better outcome to those who were not, and surprisingly, this study had the data to show that. In fact, the highly motivated patients, the ones that maintained less than 10% fat, that exercised 3 to 4 times a week, that kept their LDLs less than 90 whether they took the lipid medicine or not, after 5 years only had a 6% risk of a cardiac death or an intervention. Those that were in the moderately motivated group - they only exercised a little bit, they did not take their lipid medications, but they still did a little bit better. This group had a 30% risk of having a cardiac event, and those that did not do anything, they had a 60% increased risk of a cardiac event.
The reason why this study is important is because it looked at motivation. So many times when they do randomized studies, they put the patient in one group or the other, but they do not look at the patient and how motivated they are to affect their health.
This was a study that looked at the perspective from the patients point of view: Some of the reasons that the patients are not happy are that they feel that their opinion might be ignored or their preferences not respected. Patients felt disrespect from the people that they were dealing with; not good communication, like that patient who said, "I can't afford the medicine."
How adults learn
A key point, and you have seen lots of good information during this conference about patient education, is that how patients learn is many times not considered. When we are developing a plan we often decide what a patient needs to know and we simply hand them some information. That is not how adults learn. When you are building a plan, if you can incorporate things that the patients can take home with them where they can see some of their own information, then you get a better reception.
Avoid pointing fingers
This is a cartoon that says, "Yes! I exercise daily. Yes! I cut down on fatty foods. Yes! I watch my salt intake? Now let me ask you a question?Do you?" It is hard for patients. You sit there and point that finger and whatever, but that is not how we motivate patients. When developing programs, you have to think about that.
Helping adults learn
This is another way of looking at patient education, is that adults learn differently than children. They bring a wealth of past experiences. You have to get to the doctor inside of everyone's head.
Obstacles to learning
These are some of the obstacles to learning. Of course, you have to take in consideration different cultures. Sometimes the best way of doing that is whether it is a patient with a different culture or not, to try to understand where that patient is coming from.
Perspectives of chronic illness
Then you can get a better aspect of where they are coming from.
Whether you want to volunteer or not, I think that CKD awareness is an important aspect of the care that we give. If we can develop a good relationship to all the patients out there and help identify the patients early, that is the key.
Recognition of CKD is key
This study looked at a regular internal medicine practice, and they looked at the identification of CKD patients in that practice. The caregivers identified only 22% of their CKD patients as having CKD. After they received some education about CKD and looked at patients who were at risk and helped to identify them, it turned out that they could identify 85% of their patients with CKD. So this is also a way for us to get out there and talk to other practices.
I do not know if anyone has been involved with KEEP programs. The National Kidney Foundation is down in the exhibitors' hall if you want to approach them and talk to them about that, but if you have not been involved with this, it is a wonderful way of being involved. This is a way of screening in a population that is at an increased risk for chronic kidney disease.
In our practice now, we have over 4000 CKD patients. We manage them at 8 different dialysis units in our formalized CKD program that has about 300 patients. In our anemia program, we have 200 to 300 patients where we take care of those patients at about 48 hours of RN time, and our average hemoglobin is about 11.8 g/dL. We see patients in 8 different dialysis units, that is about 700 patients. The reason why I am going through this is because we talked a lot tonight, but what I am going to do is bring it home. Bring it down to the reality. We learned a lot of information but I am going to try to bring it to how we can make this happen.
History of the WNERTA anemia program
The history of our anemia program: We started in 1997 and there were 8 patients in May. As that population grew in 1999, we had about 40 patients and what we did is that we then contracted nurses. We paid them per injection and had them come for half a morning a day. That is how we started our program. You don't have to change your whole job. If you are working 24 hours, you might want to do a part-time arrangement and approach a nephrologist.
In 1999, we then developed our formal CKD program, and those patients get referred in by MDs. I also utilized my anemia patients who were already in the office. We developed guidelines and tracking tools.
By 2002, for our anemia patients, we were up to 140 patients with 20 hours of nursing time.
WNERTA: Epoetin dosing frequency
And this is where we are now. This is my graphic, so it is not that wonderful. These are all of our patients from the patients who have started initially to what patients we have now. There are 274 patients. If I break that down, 40% are the 1-weekers, 21% are the 2-weekers, and the number of 4+ weekers is about 36%. The 1-weekers are the patients who we also have coming in and getting IV iron. That is why they are assigned to a once-a-week dosing schedule. Three of those patients who were dosed once week have now started dialysis, and there are also 10 study patients, where it is required that they come in once a week.
WNERTA: Epoetin after 4 months treatment
If I look at my population after 4 months, only about 23% are 1-weekers, 2-weekers are at 20%, and 4+ weekers are at 54%. So close to 79% of the patients are 2- to 4- weekers. If I had gone back and done 6 months, which I probably should have done, I am sure there is a population of the 1-weekers who have now bumped up into the 2 weekers. The benefit of this is that it is a benefit to the patient. The clinic would make a lot more money if I had those patients come in every single week. But for the patient's benefit in terms of quality of life (they are elderly) this is a benefit for them.
Suanne, get me some help.
This is Phyllis, our anemia nurse, ready to do a stick on a patient. We are going to test her own blood count right then and there. This way it makes it easier to add medications and it only takes a couple of minutes before we get the results and then we can add to a patient's epoetin dose accordingly.
This is a tracking tool that we utilize to track the dose of the epoetin they are on as well as some of their iron store measures, when they were last given iron and what the results of their tests of their HemoCue.
Happiness of once-a-month dosing
This is a little lady that is 87 years old that wanted me to say "hi" to everybody. Very happy coming in once a month.
Quality control and monitoring inventory
You most certainly have to have quality control. You have to have mechanisms to go and monitor your inventory and your stock. We are now looking at a computerized type of system. We do have everything on tracking tools, but they can be an expense and you to account for every drop.
Patient empowerment tools
Patient empowerment - what we utilize for patients and getting the patient into the system for teaching. I have a big 17-inch screen laptop and I am able to show the patients there our recent data that also gets incorporated into their charts.
This is a flow sheet that I am able to have in the chart. It is broken into the different stages of CKD. There is QI on the side here, so that over one year's time I can tell what my average hemoglobin is, what my irons are looking like, what the kidney function is, and so it is a good tracking-type tool. I have that for all stages of CKD. The most important part is I have that chart enlarged. I show it, sitting with the patients. The patients buy into it, so they can flip back and forth. We can look at their data. It is a simple excel spreadsheet.
Over here, I know it has it all typed in, but that information is usually not typed in. That is what we call the negotiated plan. Over here, there is a segment for their blood pressure for what their anemia is, for what their bone disease is. It goes by color code: green is good, yellow is caution, red is bad. I take their recent lab data. We plug it all in before their visit and then it gives us something to talk about or to negotiate during the visit. If let us say the patient's blood pressure is elevated and I want to increase their Diovan (valsartan) and they say, "No! I didn't take the medicine today." It is like "Okay. Well, why don't you come back in 2 days, we will see how your blood pressure is." That is why it gets the patients' input. We are able to then take this home as a reference tool. This is what I have done with patient education. If you are in the outpatient world, you have wonderful information out there, but you get stuck in the different cupboards. No one hands the patient the information right and you know someone is not going to go run across the office to get that right piece of information.
Patient education tools
What I have done is I put this big huge book together, I call it Kidney Klass, and yes it is spelled with a K, and the doctors do not like that. What we have done is put each of those pieces of information in like a plastic-type sheet with a number associated to it. This is out in the waiting room so the patients can sit there. They can flip through it.
More patient education
They say, "Oh, maybe I want some more information about anemia," and so they can to go the secretary and ask for whatever number, and so she will get that from the file cabinet. Why does this work? Because patients learn when you give them information what they want. If they are not going to learn, if I am giving them patient information about anemia and that is not what they want at that time. If they want to know about exercise and they find that, that is when learning occurs.
Vascular access teaching
This is where we bring in some of the modality type of teaching we do about vascular access. We do some vascular vein mapping preemptively to get an access in.
Communication - we developed some communication tools that are not used there in the office but also are used to help educate the primary care doctors that we work with.
That is one of our nephrologists.
Here we are doing some community outreach. We have been involved with formal fairs where we do KEEP screenings. We have done 5 of those, I believe, but we also do health fairs. If there is some high risk populations we have done it with a lot of churches. We will go and do some screenings.
Nursing is the answer
Nursing is the reality. Nursing is the answer.
So thank you very much.
Moderator: Let us give a hand for Suanne and thank Suanne for an excellent presentation.
- IV. NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease: update 2000. Am J Kidney Dis. 2001 Jan;37(1 Suppl 1):S182-238. Am J Kidney Dis 2001 Aug;38(2):442.
- Macdougall IC. How to improve survival in pre-dialysis patients. Nephron. 2000;85 Suppl 1:15-22.