ANNA 36th Annual National Symposium

Complications of Anemia and the CKD Patient
Part One of Two

Suanne Petroff, RNCS, FNP, CNN
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This offering for 1.5 contact hours is being provided by the American Nephrology Nurses Association (ANNA), which is accredited as a provider and approver of continuing education in nursing by the American Nurses Credentialing Center-Commission on Accreditation (ANCCCOA). This educational activity is approved by most states and specialty organizations that recognize the ANCC-COA accreditation process. ANNA is an approved provider of continuing education in nursing by the California Board of Registered Nursing, BRN Provider No. 00910; and the Kansas State Board of Nursing, Provider No. LT0148-0738. This offering is accepted for RN and LPN relicensure in Kansas.
Date of Original Release: October, 15, 2005
CE Credit Eligible Through:October 15, 2006
CE Credit Hours/Completion Time: 1.5
Target Audience: Nephrology nurses and technicians.
Method of participation: Listen to the talk, read the PubMed abstracts of linked slides and references, take the post-test, and complete the evaluation form.
After participating in this program, the learner should be able to:
  1. Discuss the scope of chronic kidney disease (CKD) and its comorbidities
  2. Implement new approaches to manage the anemia associated with CKD
  3. Describe the role of the nephrology nurse and other members of the collaborative team in the screening, diagnosis, and management of anemia
  4. Examine ways to partner with patients in self management of CKD
  5. Improve the awareness and decision-making of patients with CKD
Suanne Petroff: Advisory Board: Ortho Biotech; Grant support: Ortho Biotech; Speakers Bureau: Ortho Biotech.

The CE policy and disclosure statements of ANNA are given in detail on the Symposium Home Page. The CE policy statements of HDCN are listed on this page.


Complications of anemia and the CKD patient
To begin with, I want to thank everyone for being here tonight. I know it is the last night of a wonderful conference. ANNA has done a wonderful job and I have really enjoyed all the programs that I have gone to. Patient empowerment and patient education is something near and dear to my heart, and so I have really enjoyed that. I would like to also thank Ortho Biotech for sponsoring this program and once again they have been a real support for all of us nurses out there who are practicing.


If we can get going, I would like to say, once again, welcome!


Learning objectives
The true learning objectives tonight are that we are going to discover or discuss the scope of practice with CKD. We are going to implement new approaches in anemia management and learn how that is associated with CKD. We are also going to describe the role of the nephrology nurse and other members of the collaborative team because that is what we are all about. We are also going to examine ways to partner with patients in self-management, and improve awareness and decision-making for patients with CKD.


This is what United States looked like in 1996. You do not really have to see all the little demographics, but just think about it - CKD = dark = bad.


Geographic distribution
This is what we look like five years later - kind of scary.


Mokdad AH. et al. Diabetes Care. 2000 Sep;23(9):1278-83.
Prevalence of type 2 diabetes
At the same time, look at diabetes, once again dark = bad. This is from 1990 to 1998. We are definitely growing.


If you look at the weight of our population, men and women, we are being super-sized. We are seeing this more and more in our CKD practice. You are seeing teenagers coming in with proteinuria, getting heavier.


Incidence of ESRD
Let us look at the incidence. We have all seen this graph a lot of times. It shows that there is a rising prevalence of patients with CKD. Causes of CKD: Diabetes and hypertension are the main two causes of CKD. Although our diabetic population is growing, you can see that the CKD rate the nondiabetic population is growing also.


Measures for defining CKD
Let us look at measures that we measure kidney function with. I know there have been some really wonderful CKD programs here throughout the whole symposium. If I am repeating the message of some of the other wonderful programs, I am sorry.

Just to get a base for everybody - measures for CKD. We are looking at GFR, called glomerular filtration rate. This is actually the blood filtration rate through the glomeruli. It is the best way of measuring kidney function. NIH has defined CKD for a woman as a serum creatinine greater than 1.5 mg/dL, and for a man, greater than 2.0. They have now gone to propose lower limits, for a man less than 1.5 mg/dL, and for a woman, less than 1.2, so a creatinine clearance less than 70.


Epidemic of kidney disease
Question: How many people have seen this throughout the whole couple of days? No? This is looking at what the GFR is in the different stages of CKD according to the K/DOQI guidelines. Over here is what the GFRs are as well as your stages. You will notice that the millions of people, when you are looking where most of the patients are, are right here in stages II through III. If you get a visual of this, thenthis is what it looks like. I love this visual because it really gives you a good idea of the population of patients with CKD, and granted it can be very scary thinking that this population underwater is then going to make it to the top of the iceberg, but in reality the number of patients who are on dialysis lessens in stage V, because a lot of those patients in stage III and stage II are going to die before they even end up getting to stages IV and V. That is what we are talking about today, what things can we do to prevent patients from dying before they get to stage V?

This is looking at some of the comorbidities in patients with predialysis or CKD and we have already talked about hypertension and diabetes, but also CHF, angina, chest pain, and you will know that that is often related to anemia; most of those problems will be associated with anemia.


Adjusted hazard ratios
Hospitalizations. This is very interesting to, of course, a lot of insurance companies out there. If you look at the risk for these patients as your kidney function goes down - I believe this was done using patients from Kaiser - they are at greater risk for hospitalizations, cardiovascular disease, and also death. This is your stage V, this is your stage IV, and they actually broke apart stage III because there is a higher risk in that population.


Medicare CKD patients
Sometimes we think the worst thing that can happen is, I have heard it described as, protecting my patients from the D word. Actually the D word means death. If you look, right here is your risk for going onto dialysis, ESRD. Here is your risk for death. If you take a patient that is not a diabetic, but has CKD, their risk for dying is 2.4 versus starting dialysis at 2.25. Diabetes, greater risk 29% of the patients will go and die before they on to dialysis, so that is striking.


Reducing mortality
What is our goal here? This is what we are all talking about - how do we reduce the mortality in patients with CKD?


Pereira BJ et al. Kidney Int. 2000 Jan;57(1):351-65.
Comprehensive CKD care plan
This is one of my favorite slides. I use this all the time. For the sake of this talk, I would love to be able to be here all night. All these other aspects of prevention are very very important and we most certainly have incorporated those into our CKD program. For the purpose of this talk, when we are talking about ways to educate and empower the patient, we are going to be focussing on anemia. Anemia comes under ways to prevent complications. Of course, that is going to tie into cardiac and vascular disease.


Am J Kidney Dis 2001 Aug;38(2):442.
What are some of the factors that cause anemia? We know there are lots of factors that causes anemia, but most of the two top are endogenous erythropoietin and iron deficiency. Most certainly when you are working your patient up for anemia, you really have to make sure that is not because of severe hyperparathyroidism or aluminum toxicity or hypothyroidism. If they are not responding to medication, make sure you are also looking for those, but really the top two are endogenous erythropoietin and iron deficiency.


How does this work? When the kidney is functioning well, it senses the blood flow through the kidneys. If it does not have enough blood flow, then what happens is that it goes and stimulates erythropoietin to go and act on the cells to produce bone marrow and develop new red blood cells. When you have an adequate amount of blood, that then induces the kidney to turn off the production of erythropoietin.


Normal erythropoiesis
The same thing is going on with the liver - you then have the liver and other ways too of releasing the iron that also you will need in the bone marrow to develop new red blood cells.


RBC development
This is a new red blood cell. Red blood cells take 25 days to completely develop. They start from stem cells from the bone marrow. They then develop into burst-forming erythrocytes. At that time, they need erythropoietin to then stimulate them to become colony-forming erythrocytes, and at the proerythroblast stage is where they then get exposed to iron. We bring in the iron into the red blood cells and make the hemoglobin, and then you have a mature red blood cell. You need both erythropoietin and iron to really make red blood cells.


Prevalence of anemia in the general population
What is the prevalence of anemia in United States? This is the general population. You always think that it is the women who are anemic, yes. We have it rough ladies, but we only have it rough until about we are 74. We win the anemia prevalence contest until about age 74 and then from the ages of 75 to 85, men are more anemic than we are. It is predicted that, by the year 2030, this group will increase by 20% and this group, 85 years of age plus, by threefold. There are going to be a lot of anemic people in United States!


Anemia in the US population
What are some of the etiologies for anemia in the elderly? There is a large percentage that is due to chronic kidney disease or EPO deficiency. Here they have kind of interwoven chronic disease and chronic kidney disease. When they show ACD (anemia of chronic disease) which also means that iron status is okay but patients still have low hemoglobin, they have kind of lumped theses patients with patients who have CKD. There is a large population who have anemia due to chronic disease - what does that matter, whether it is an elderly without a chronic kidney disease, whether it is your dialysis patient, or whether it is our CKD patient?


Risk of falls
This is a study that was done in a New York hospital, and it looked at hip fractures. Everyone that is over 65 years old that came in and that had a hip fracture, they divided them up into whether it was caused by a fall or if it was not caused by a fall. Then they broke it down whether it was because the patient was anemic or not anemic. You can see that falls occurred in 30% of anemic patients versus in 13% of patients who were not anemic. This means that the anemic patients had a threefold increase in the risk of falls. If you just increased your hemoglobin by 1 g/dL, you had 45% decreased risk of falls, so that was pretty significant. Think about it. Your dialysis patient with a low blood count, they fall, they are in the rehabs, or CKD patients that are elderly and taking care of somebody else at home. These are the patients that are at risk.


Stump TE et al. J Am Geriatr Soc. 2001 Jul;49(7):934-40.
Cognitive impairment
What about cognitive impairment in the elderly? What they did is that they went and they gave elderly patients a test. There are over 4000 patients in this study; they were 65 years or older. If you answered all but two questions right you were declared to have no impairment. If you had greater than five questions wrong, then you were defined as having moderate-to-severe impairment. You can see here that those patients that had moderate-to-severe impairment were more anemic. What we are expecting our patients to do that are anemic is to care for themselves, to take the medications like we want to, to come to the doctor's office like they are supposed to.


Thomas MC et al. Diabetes Care. 2003 Apr;26(4):1164-9.
Anemia in diabetics
The prevalence of anemia is definitely higher in patients who are diabetic versus the regular population.


Anemia in CKD
When we look at prevalence of anemia in CKD, this was a study where they looked at 237 sites, there were over 5000 patients, the mean average age was 68 years old, 53% women, 22% black, and the primary comorbidities were diabetes and hypertension.


PAERI study
About 50% of these patients had a hemoglobin less than 12 g/dL, and 8.9% had a hemoglobin less than 10 g/dL. What does that mean when you break it down by GFR? If you looked at their stages of kidney disease or their GFRs, as these patients' kidney function got worse, they were at much higher risk for anemia. So as your GFR goes down, you are at a much higher risk for having a hemoglobin less than 12 g/dL, and also to be in the lower group, with a hemoglobin less than 10. Also, women and blacks were found to be at much higher risk to be anemic than the general population.


Reducing mortality
Reducing mortality in patients with CKD is really what we all are here about. Anemia is associated with increased morbidity and mortality. We want to look at ways that we can improve our outcomes. We want to look and see if we do improve patient hemoglobin, is it really going to make a difference.


Thomas MC et al. Diabetes Care. 2003 Apr;26(4):1164-9.
Cardiovascular mortality
This is looking at cardiovascular mortality as a function of GFR when the patient's GFR was relatively high - we are talking between 90 and less than 70 ml/min. I think these patients were followed for 16 years. A patient with a GFR less than 70 ml/min had a much higher risk for mortality than a patient with a GFR between 70 and 90. So mortality risk increases with lower GFR, and it does not even have to be a low GFR.


Sarnak MJ et al. Am J Kidney Dis. 2000 Apr;35(4 Suppl 1):S117-31.
Kitiyakara C et al. Curr Opin Nephrol Hypertens. 2000 Sep;9(5):477-87.
Cardiac disease in CKD
What are some of the traditional risk factors for cardiac disease in CKD? We all know these - we have all learned these before in nursing school a million times, diabetes and hypertension. When we look at some of the nontraditional causes we find anemia, inflammation, and reactive oxidative stress, which is really difficult to evaluate. We most certainly can be looking at PTHs in patients who are at risk for hyperparathyroidism, but anemia is a very measurable risk factor for cardiac disease in CKD.


Silverberg DS et al. Eur J Heart Fail. 2002 Dec;4(6):681-6.
Cardio-renal anemia syndrome
What you have going on is kind of like a triad, where congestive heart failure makes chronic kidney disease worse, and this makes anemia worse, and vice versa, back and forth. We see this all the time.


Erslev AJ et al. N Engl J Med. 1991 May 9;324(19):1339-44.
Consequences of anemia in CKD
When we are looking at some of the cardiovascular effects of CKD, we look at LVH and some of the factors that can cause CHF. We most certainly know with our patients that their anemia gets worse and that they are more likely to have angina. Also, we have to look at the reductions in functioning of these patients and how they are functioning. You have heard from some of the programs today that the patients who are anemic are not able to perform their normal activities - they have to take naps all the time, and their general well-being is decreased. Sometimes patients associate this with getting older, "I am just getting older, I cannot do as much as I used to."


Coresh J et al. Arch Intern Med. 2001 May 14;161(9):1207-16.
Cardiovascular care in CKD patients
When we look at some of the cardiovascular care aspects of LVH, we know that decreasing hemoglobin by 1 g/dL puts one at a 6% higher risk for worsening LVH. We have always heard about high blood pressure as a risk factor for LVH; however, by increasing blood pressure by 5 mmHg you only get a 3% rise in risk. Most certainly that puts you at a higher risk. We know that as someone's kidney function gets worse and when they start dialysis, they are at much higher risk for LVH. We know that 11% of CKD patients on blood pressure medicines are not even achieving target blood pressures, and the target BP according to JCN-7 is now 130/85; of course that is even lower for your diabetic patient. LVH is definitely a risk in CKD.


Risk of cardiac death
This shows that the risk of cardiovascular death as a function of anemia. As your hematocrit goes down, you are at a higher risk for cardiac death.


You are not doing any better with strokes either. If your kidney function goes down less than 60 ml/min and if you are anemic, then you are at a much higher risk for strokes.


Anemia is costing you, it is costing me, and it is costing the insurance companies - lots of money. They talk about cost of medicines and cost of hospitalizations, but look at this, just with a hematocrit less than 33 you have a much higher risk for getting into the hospital and much higher risk for dying.


Gouva C et al. Kidney Int. 2004 Aug;66(2):753-60.
Anemia treatment and CKD progression
This looked at anemia treatment and CKD progression. Does it really make a difference? Is it going to help preserve residual kidney function? A lot of our patients are going to ask us that. They ask sometimes when we are giving them medications - does it really make a difference?


Gouva C et al. Kidney Int. 2004 Aug;66(2):753-60.
Early initiation of EPO
This study looked patients with early initiation of EPO versus patients who were not started initially on EPO. These were predialysis patients. They did not use diabetic patients. The reason why they did not use diabetic patients is because they did not want to have the confounding effect of ACE inhibitor usage, because of the correlation sometimes found between use of ACE inhibitors and anemia. Since ACE inhibitor is a goal standard to use in diabetics, the people who designed this study did not want to skew the results.

Patients entered this study when their hemoglobin was 9 to 11.6, and their target hemoglobin was 13. The investigators followed these patients for 12 months. The endpoint of the study was when patients doubled their serum creatinine, started on renal replacement, or died.

Conclusion: After 12 months, they found that in the patients who were treated with EPO, the serum creatinine clearance was 12.9 mg/dL versus 16.1 in the untreated patients. In the patients treated early with EPO there was a 60% reduction in risk of starting renal replacement or death.


NKF-K/DOQI target hemoglobin levels
We all know the NKF-K/DOQI target hemoglobin value is greater than 11 g/dL. It does not matter what ethnic background you are - no one is achieving this goal among CKD patients.


Kazmi WH et al. Am J Kidney Dis. 2001 Oct;38(4):803-12.
Anemia at first nephrology visit
How about the patients who start treatment in a nephrology practice in a CKD program? How are they doing? At their first visit 60% of them had a hematocrit less than 36% (and 40% had a hematocrit less than 33%). So how did they do afterwards?


Kazmi WH et al. Am J Kidney Dis. 2001 Oct;38(4):803-12.
Anemia followup
These were patients being followed in the Boston area. Eighty percent had hematocrits below 36%, and 60% were not meeting a target hematocrit of 33%, so even the nephrologists have not been doing a good job.


Kausz AT et al. Am J Kidney Dis. 2000 Dec;36(6 Suppl 3):S39-51.
Anemia care
This study looked at over 65,000 patients. Once again looking at K/DOQI target hemoglobins and those patients who have been treated with EPO. Only 28% of CKD patients are actually treated with EPO and their hemoglobins average 10 g/dL. In the other 70% who have not been treated with EPO, the average hemoglobin is about 8 g/dL.


Macdougall IC. Nephron. 2000;85 Suppl 1:15-22.
Undertreatment of anemia
We know some of the factors that contribute to undertreatment of anemia. Severity of anemia is unappreciated. You can see that if the patients are going to their primary care doctors or internal medicine. There is a large group of elderly patients and many elderly patients are anemic. What is the big deal? The cost. Sometimes people worry that if I start the patients on a medication it is going to cost the patient too much. Sometimes there are concerns about hypertension. I am going to start someone on medication and increase their blood pressure.

Also, I think there is lot to the logistics of drug administration: How many people have seen that? Nobody? I will give you some examples because I have seen it. The patient who goes into the hospital, is started on medication, and then the resident or the doctor goes and gives them a prescription for Procrit (epoetin alfa) - "Take it to the pharmacy, get this medicine". They have Medicare, they go to the pharmacy, and the pharmacist says, "Oh, that will be a 1000 dollars" or whatever it is.

I have just learned on the trip here of an interesting story too. This is the benefit of nursing and listening to patients. There is a patient who came in - it could have been the same type of situation. I do not really know if the patient was my patient. I do not know whether I will have to go back and check how she came into the program - but she had been started on epoetin when she was in the hospital. Then someone wrote the prescription and then she actually went out and purchased medicine. Her insurance did not pay for the medicine, but you know what? The doctor wrote the prescription! For three years she has been paying for the medication out of her own pocket. She goes to the doctor's visit time after time saying, "You know, the medicine is really expensive." Doctor says, "You need it." She keeps on paying for her medication. I really think there is a lot in the logistics, whether it is the communication and the caregivers just write something and think the magic just happens. This is a really important issue.

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  2. Pereira BJ. Optimization of pre-ESRD care: the key to improved dialysis outcomes. Kidney Int. 2000 Jan;57(1):351-65.

  3. 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.

  4. London R, Solis A, Goldberg GA, Wade S, Ryu S. Health care resource utilization and the impact of anemia management in patients with chronic kidney disease. Am J Kidney Dis. 2002 Sep;40(3):539-48.

  5. Stump TE, Callahan CM, Hendrie HC. Cognitive impairment and mortality in older primary care patients. J Am Geriatr Soc. 2001 Jul;49(7):934-40.

  6. Thomas MC, MacIsaac RJ, Tsalamandris C, Power D, Jerums G. Unrecognized anemia in patients with diabetes: a cross-sectional survey. Diabetes Care. 2003 Apr;26(4):1164-9.

  7. Muntner P, He J, Hamm L, Loria C, Whelton PK. Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol. 2002 Mar;13(3):745-53.

  8. Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis. 2000 Apr;35(4 Suppl 1):S117-31.

  9. Kitiyakara C, Gonin J, Massy Z, Wilcox CS. Non-traditional cardiovascular disease risk factors in end-stage renal disease: oxidate stress and hyperhomocysteinemia. Curr Opin Nephrol Hypertens. 2000 Sep;9(5):477-87.

  10. Erslev AJ. Erythropoietin. N Engl J Med. 1991 May 9;324(19):1339-44.

  11. Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med. 2001 May 14;161(9):1207-16.

  12. Silverberg DS, Wexler D, Iaina A. The importance of anemia and its correction in the management of severe congestive heart failure. Eur J Heart Fail. 2002 Dec;4(6):681-6.

  13. Gouva C, Nikolopoulos P, Ioannidis JP, Siamopoulos KC. Treating anemia early in renal failure patients slows the decline of renal function: a randomized controlled trial. Kidney Int. 2004 Aug;66(2):753-60.

  14. Kazmi WH, Kausz AT, Khan S, Abichandani R, Ruthazer R, Obrador GT, Pereira BJ. Anemia: an early complication of chronic renal insufficiency. Am J Kidney Dis. 2001 Oct;38(4):803-12.

  15. Kausz AT, Obrador GT, Pereira BJ. Anemia management in patients with chronic renal insufficiency. Am J Kidney Dis. 2000 Dec;36(6 Suppl 3):S39-51.

  16. Macdougall IC. How to improve survival in pre-dialysis patients. Nephron. 2000;85 Suppl 1:15-22.