Taking Control of Chronic Kidney Disease: Beyond the Kidney
ANNA Meeting - Orlando Florida, May 25, 2002
The Scope of the Cardio-CKD-Anemia Triad
Sally Campoy: I’m very pleased and proud to announce a panel of distinguished professionals that are going to talk about their experiences with a proactive approach on how they took control of chronic kidney disease, and applied a multidisciplinary approach for better outcomes for their patients. I’d like to introduce Dr. Anton Schoolwerth, he is the Sir Hans A. Krebs Chair of Nephrology at the Virginia Commonwealth University and Vice-Chairman of the Department of Internal Medicine. He serves as the Medical Director of the Clinical Trials Institute of Virginia Commonwealth University and is also the Medical Director of the GAMBRO Downtown Dialysis Center in Richmond. Dr. Schoolwerth received his Doctor of Medicine degree from Harvard Medical School in Boston, Massachusetts, and his Master of Science degree in health administration from Virginia Commonwealth University. Please join me in welcoming Dr. Schoolwerth, who’s going to talk about the medical aspects of CKD.
ANTON SCHOOLWERTH: Thank you very much. Good evening everyone. As those of you working in dialysis know, there's no lack of patients for us to deal with.
Population of patients with end-stage renal disease (ESRD) is growing
These are the numbers that were generated from the USRDS and extrapolated to the future. In the year 2000 there were over 300,000 Americans on dialysis in the United States, and the projections are that this number will almost double by the year 2010. The is an increasing number of patients coming onto dialysis each year, and the only reason the prevalence, the total number, is not higher, is that we still have a remarkable problem with how poorly our patients do.
Primary diagnosis for patients who start dialysis
As you know, the majority of our patients have diabetes. Hypertension is the second leading cause of end-stage renal disease. And as you see glomerulonephritis, cystic disease, and other conditions comprise the remainder.
Survival in ESRD
If you look at the longevity of a 55 to 64 year old patient starting on dialysis in the United States compared to individuals of that age from the population at large, who have a lifespan of approximately 21.6 years of additional life to go. End-stage renal disease does a little bit better than lung cancer but worse than colon cancer in terms of its survival. The average end-stage renal disease patient lives five years from starting dialysis if that individual starts in his late 50s. So we have a mortality rate, as many of you know that's about 20 to 22 percent per year. And the majority of our patients are dying from cardiovascular complications.
Many of you may have seen this slide; this plots the annual mortality rate from cardiovascular disease as a function of age, starting at the left in the 20s, moving up into the 80s. And we see on the yellow lines that not surprisingly our mortality rate from cardiovascular disease increases as we age. There are slight differences based on gender and race, but we all have a higher risk as we get older. But contrast the general population with the dialysis population which is shown in green, and you see a much flatter line and what's disturbing is that the young dialysis patient, the 30 year old dialysis patient has the same annual mortality rate as a 75 to 80 year old individual from the population at large.
Still too much emphasis on the tip of the iceberg
It struck many of us in the nephrology community recently that perhaps our emphasis, if we were going to impact on this, should be to look earlier than at the end-stage. Rather than looking at the tip of the iceberg, with the implication that our patients' cardiovascular risk began the day they had their first dialysis, it was likely that this began much earlier, at an early stage, perhaps at the stage when they first developed the risk factors that led to their progressive kidney disease. And so with that kind of background, there has been a great movement that was spearheaded by the National Kidney Foundation to look at chronic kidney disease.
Goals of CKD therapy
I'll take a quick aside for those of you who are wondering why we're calling this chronic kidney disease instead of chronic renal failure, chronic renal insufficiency. This was the recommendation that came out of the K/DOQI advisory board, the publication that came out of the ... in the American Journal of Kidney Diseases in February that we use the word 'kidney' rather than 'renal' or 'nephrology'. This is a word that's recognized by the population at large to a much greater extent than renal. At least we can get people thinking about what organ we're dealing with. But the terms of our goals in chronic kidney disease is not only to delay the onset of end-stage renal disease, but really to decrease cardiovascular risk, because that actually has a much greater impact. As I'll show you in a few moments there are many more people who have chronic kidney disease, and are at risk of developing end-stage renal disease. But many of these are going to die of cardiovascular disease even before they reach end-stage disease. So if we can identify these people that's a major plus. To do this will involve empowering and educating patients, and as we collectively approach this, the hope is that we'll improve the overall quality of life of our patients.
Chronic kidney disease(CKD)
Now chronic kidney disease is common. I'll show you some data on that in a moment. It has significant morbidity. The treatment is expensive and it's particularly expensive if the patients are not identified and treated early. And what's particularly important is that we now have effective treatments that can slow the progression of disease, and can reduce cardiovascular morbidity. But to do that entails a team approach. And you're going to hear this evening how at least at one institution we've tried to address this using a team of effort to help our patients.
Stages and prevalence of CKD
Now this is a similar slide to what Sally showed you a few moments ago, and this is I think a very important slide because it comes from the CKD guidelines from the K/DOQI advisory group, and what I want to start with is over on the right and then I'll come back to the left part of the slide. Based on some epidemiological data that have been collected through the so-called NHANES study on a periodic basis, we have information on the number of individuals who have chronic kidney disease. There are a lot of different numbers here and it's based a little bit on how the screenings were done. But it involved a cross-section of the population who had among other things, creatinines measured and protein measured in their urine. If one urine was tested and used as the sampling, it led to a higher prevalence. But the point here is these numbers are in thousands. And in contrast to 300,000 Americans on dialysis, we're talking about millions of Americans who have chronic kidney disease.
And to summarize this figure, the National Kidney Foundation estimates that there are 20 million Americans who have chronic kidney disease, most of whom do not know they have it, and another 20 million who are at risk.
Now in order to develop a more systematic approach to not only identifying but then treating these patients, the NKF has recommended that we stage these patients based on their glomerular filtration rate. And if we use a value above 90 as normal, people can still have chronic kidney disease, if they have evidence of damage to the kidney, such as protein in the urine, albuminuria, proteinuria, and that would be at stage one. But as the glomerular filtration rate decreases, as the disease progresses, the stage increases and they have proposed five stages down to level five, which is when the glomerular filtration rate is below 15 mLs per minute. And that's the level at which patients are very close to if not already needing dialysis. So the goal is to reduce the number of people that reach stage five by finding them, by identifying their disease at an earlier stage where we might have a good way to impact their progression as well as their cardiovascular risk.
Why classify severity bylevel of GFR?
Now, why classify according to the glomerular filtration rate rather than just the serum creatinine? First of all, the GFR is accepted as the best overall measure of kidney function. The kidneys filter blood, they remove impurities, and they pass them into the urine. The rate at which the kidneys filter is a good measure of kidney function. It's easier to explain to our colleagues, both professionals and public and patients that the kidney acts as a filter. Conceptually we have a better chance of explaining that than by trying to explain this creatinine test goes up when the kidney function goes down. So when the filter goes awry, we filter at a lower level. And, ultimately the goal is to have patients know their number, know their glomerular filtration rate in the same way that patients through other education programs have come to know what their cholesterol is, what their blood sugar is, what their blood pressure is. Our goal is to have them become as familiar with their GFR as with these other numbers.
Patients at risk
Now who is at risk for chronic kidney disease? We have excellent information to indicate that there are well known risk factors in these patients, the patients at risk, that are the ones that need to be screened and looked for. Diabetes, hypertension, remember those are the leading causes of end-stage kidney disease, are also the leading causes of chronic kidney disease. A family history of diabetes, high blood pressure, or kidney disease is itself a risk factor for developing CKD in an individual. And we know that given those factors if one is above 60 years of age or of a minority group that the risk is even higher. Now these risk factors do not negate other risk factors that are also important. High protein diet may impact obesity, hyperlipidemia. The kidneys now have been added to the list of conditions that are affected by smoking. We have excellent epidemiological data that smoking poses a risk factor for kidney function. And, of course, drug use, both illicit drug use and nephrotoxic drugs such as over-the-counter pain killers, non steroidal inflammatory drugs for example.
Recommended screening tests for patients for CKD
Now, the recommended screening tests for patients at risk is shown on this slide. The test that will allow us to estimate the glomerular filtration rate remains the serum creatinine. Serum creatinine normally runs between 0.5 and 1.2 milligrams per deciliter but as I'll show you in a moment, that narrow range is not very sensitive at picking up early stages of kidney disease; the stages at which our goal is to find the patients. Blood pressure, blood sugar, urinalysis, and particularly as part of that urinalysis, a measure of albuminuria or proteinuria is essential.
Improving on the serum creatinine screening
Now, this is one of several formulas. Sally mentioned the MDRD equation. This is the so-called Cockcroft-Gault equation. We'll find out I think in the next year or two which of these equations becomes the primary recommended one, but at least for those of you who just do things arithmetically with a calculator, this is a little easier to work with. But it estimates the creatinine clearance from the serum creatinine, but adjusting for the patient's age, body weight, and it really should be ideal body weight, and then the gender, male or female. And I have an example here at the bottom just to show you how a marginally elevated serum creatinine or in some cases a serum creatinine that's even with the normal range can be misleading if one does not calculate the creatinine clearance or GFR; an 80 year old woman, 50 kilograms in weight, with a serum creatinine of 1.5 milligrams per deciliter. One would say 1.5 is just a little bit above normal, but if you factor that into this equation, this individual has a creatinine clearance of 24 mLs per minute. This is stage 4 chronic kidney disease. This is advanced kidney disease, but because this individual is elderly and a female, she has less muscle mass to generate the creatinine, and so it's easy to be misled if we just look at the serum creatinine. The same individual with a serum creatinine of 1.2 would still have stage 3 chronic kidney disease.
So, the goal is to have everybody calculate this, and actually the Kidney Foundation has recommended that clinical laboratories begin to report whenever serum creatinine is ordered, report a glomerular filtration rate that corresponds to that much as an INR is reported when someone orders a prothrombin time. And that's going to take a little while but I think that should get peoples' attention.
Assessment of early kidney damage
Now in addition to measurement of function like calculation of the GFR or creatinine clearance, we can look for damage, and the best way to do that is to look for the presence of albumin or protein in the urine. Twenty four hour urines are still the gold standard, but it's appearing that we can get just about good information much more conveniently if we measure albumin or protein and factor it by the creatinine in the urine, which corrects for the dilution or concentration of that urine sample. And if that's done on a widespread basis, we're going to pick up the presence of albuminuria and proteinuria, a sign of damage to the kidney, and this will allow us to detect the presence of chronic kidney disease at an earlier stage.
CKD Detection strategies targeted at high-risk populations
So there are major movements toward for early detection, and there are several ways that this is being done, and I just have a few examples on this slide. And I'll mention the first two in a little bit more detail. The program of the National Kidney Foundation called the KEEP Program, which is targeted particularly at first degree relatives of patients with kidney disease; the relatives of dialysis patients, for example. I'll show you in a moment what's come out of that. Ortho Biotech has sponsored a study called the PAERI study, and I'll show you some more about that. That's prevalence of anemia in early renal insufficiency, that was before we came up with the CKD name. But, very interesting data.
And finally, in hospitals, where there have been a number of studies showing that patients discharged from the hospital with diseases which we know, placed in that increased risk for kidney disease, are not having urines tested, are not having creatinines much less GFRs calculated; cardiovascular risk is not being assessed. And for those of you who work in a hospital environment this is a tremendous opportunity for you to suggest to your physician colleagues that perhaps these tests ought to be ordered if they haven't been, because these patients are at increased risk for developing or having chronic kidney disease.
So let me say a bit about the KEEP Program. This stands for Kidney Early Evaluation Program, and it's now moving into several different stages.
NFK kidney early evaluation program (KEEP)
The initial plan was to screen first degree relatives. First degree relatives being parents, siblings, or children, of individuals with hypertension, diabetes, and kidney disease. The vast majority of these patients were actually recruited through the dialysis units, getting dialysis patients to get their relatives to come in for screenings. These screenings were held in churches, community centers, other places, staffed entirely by volunteers.
KEEP complete health screening
And as part of the screen, these tests were performed. Individuals had their blood pressure measured, they were weighed, and they had a blood sample obtained for glucose, a hemoglobin and a serum creatinine. They gave a urine specimen which was tested for microalbuminuria, for white cells, and blood. And, because we had a creatinine, we had a weight, and we knew their age, and race, we were able to calculate their creatinine clearance.
Now, the first widespread KEEP Program called KEEP 2 done in many parts of the country involved the screening of over 7000 individuals at 150 sites. Not all of the data is available, at least to me, but what we can tell you is that of the data that has been analyzed to this date, this is a remarkably successful program. My public health colleagues tell me if you do a screening program, the population at large, and you achieve the five percent yield you're doing pretty well. Ninety percent of individuals who came in for KEEP screening had one or more abnormalities on the six tests that I mentioned in the previous slide, outside of the normal range. And, over half of them learned of at least one new condition that they did not know about from this. This is a very high yield program, and it's extending now to the KEEP 3 where we're also looking at what happens to these individuals once identified, and suggested that they be referred for further testing. We'll find out more about the success of this program. But, this looks like it's going to be a winner.
Comorbidities of CKD
I'd like to now move on a little bit to some of the comorbidities that patients with chronic kidney disease have. And this is familiar to all of you who care for patients once they reach dialysis units, but the conditions, the comorbidities don't start there. They start much earlier, and they need to be treated earlier. Hypertension, anemia, bone disease, metabolic acidosis, and nutritional problems are the ones I'd like to briefly mention now.
Hypertension and CKD
Let's start with hypertension. As I mentioned earlier, hypertension is the second leading cause of end-stage renal disease, and chronic kidney disease in the United States. We know that hypertension can damage the disease and lead to chronic kidney disease, but we also know that patients with chronic kidney disease of other ideologies frequently ... usually develop hypertension and that elevated blood pressure can then serve to damage the kidneys further. Patients often get into a rapid downhill spiral. Although we don't necessarily have treatments in all cases for the underlying disease, we know that we can slow the course of their disease progression if we can control their blood pressure. Blood pressure itself, hypertension is a risk for left ventricular hypertrophy. And left ventricular hypertrophy, enlargement of the heart, is an independent predictor of cardiac death in dialysis patients.
Consequences of CKD: left ventricular hypertrophy (LVH)
About 75 percent of patients in the United States, adult patients in the United States on dialysis, have enlarged hearts. That's an awful statistic. But when it's been looked at earlier, in chronic kidney disease patients, it's pretty high too. It's almost 40 percent. So we can look at this, as saying it's not as bad as it is when patients start dialysis and we have an opportunity to try to reduce that number. But also if we can identify the patients with chronic kidney disease, perhaps we can impact on this 39-40 percent figure. From a number of studies, it appears that not only is hypertension a risk factor for left ventricular hypertrophy, but anemia turns out to be a risk factor itself, and interestingly, diabetes. There actually have been some investigators who've looked at this in a quantitative fashion as our glomerular filtration decreases as measured by creatinine clearance. For each five mL per minute drop in creatinine clearence, there's a three percent increase in the incidence of LVH. As the blood pressure rises by five millimeters of mercury there's another three percent increase risk for developing LVH. But look at what happens when the hemoglobin drops. For each gram per deciliter drop in the hemoglobin there's a six percent increased risk for developing left ventricular hypertrophy. This has not been recognized as well until recently.
Prevalence of anemia in CKD
Some data from Canada have really helped us pinpoint and focus on this. These are some data from Dr. Levin in Canada showing the relationship between the development of anemia and chronic kidney disease. And the point of this slide is to show you; we all know that our patients, once they're on dialysis, once their renal function is very low, almost all are anemic; but anemia in many patients starts fairly early. Up to 30 percent of patients when they're still in stage 3 with significant kidney function, will have anemia. The incidence of anemia, the prevalence actually increases as kidney disease progresses.
Anemia and LVH in CKD
From the data from Canada we see that there's a relationship between anemia and the development of left ventricular hypertrophy in patients with chronic kidney disease. And this plots the number of patients with LVH as a percentage on the Y-axis at different stages of chronic kidney disease beginning at levels above 50 and moving down to less than 25. And we see that the incidence of LVH increases, but is already substantial at early stages of chronic kidney disease and it seems to track statistically not only with decrease in disease function, but with the decrease in hemoglobin. And there's lots of other data that anemia contributes to the development of left ventricular hypertrophy. The reason that's important is that we have some data and I'll show you that in a moment, I'll at least go over it, that we can impact this if we identify this early in our patients.
Prevalence of anemia in early renal insufficiency (PAERI)
I mentioned the prevalence of anemia in early renal insufficiency study, and I'd just like to tell you a little bit about that. This was a multi center study, over 5000 patients at over 200 sites, many of them primary care sites in the United States. To be included a patient had to have a serum creatinine between 1.5 and 6.0 if a woman, or between 2.0 and 6.0 if a man. And the first 4000 were analyzed by an interim analysis. That I'll briefly review some of the findings with you.
Prevalence of anemia-PAERI study
This shows the prevalence of anemia in this group of patients. And what we see is that approximately 50 percent of the patients had anemia defined as a hemoglobin of below 12. It depends where we define the cut-off, but we used 12 as a cut-off. Almost half of the patients had anemia, and almost ten percent had hemoglobins below ten grams per deciliter. Severe anemia.
Pathophysiology of anemia in CKD
The anemia of chronic kidney disease has several potential causes, but the overwhelming reason is lack of erythropoietin. It can be impacted by iron deficiency, and we're finding out that our patients have a much higher incidence of at least functional iron deficiency, as in our dialysis patients, but earlier on than we thought. And we had to consider that. But the major reason they're anemic is because of deficiency of erythropoietin. And we can correct this.
Epoetin alfa: recombinant human erythropoietin
Administration of erythropoietin can correct the anemia, and it can be and should be used not just when patients start on dialysis, but well before that. We know that we can normalize the anemia. We're not allowed to fully normalize it, but get the hemoglobin up to about 12 grams per deciliter. And there are some preliminary studies to show that if we do this early enough we can actually see regression of left ventricular hypertrophy. So patients with enlarged hearts, if their anemia is corrected, may actually have decreases in the size of their heart. And we know from a number of quality of life studies that these people feel much better.
Phosphorus retention/vitamin d deficiency
Phosphorus retention and bone disease is another problem. We all deal with this in our dialysis patients. PTHs, phosphorus, but this starts early and we need to treat it early to protect our patients' bones. So we need to start addressing phosphorus retention by having the patients instructed on dietary phosphorus restriction. They may have and often do have vitamin D deficiency earlier than we thought. And this can contribute not only to hypocalcemia, but in itself can impact on the hyperparathyroidism that our patients have. And the recommendation is that if patients have elevated PTHs that we look for them earlier than we have and we treat by restricting phosphorus and using phosphate binders when necessary and treating them with vitamin D analogues.
Acidosis is another feature that we now know has a major impact on a long term basis on muscle and bone health. Acidosis can lead to increased breakdown of muscle, it can also accelerate and potentiate the metabolic bone disease of hyperparathyroidism. The recommendation is a fairly straightforward one. Follow the CO2 on the electrolytes and get that CO2 up to at least 22 mEq per liter with sodium bicarbonate or another base such as citrate.
Eating well and exercising
Nutrition remains a problem and you'll hear more about this from Kathy in a few moments, but I just want to remind you if you're not aware of it that HCFA has now authorized payment for chronic kidney disease patients to be counseled on dietary measures up to three visits per year. And we really need to utilize that now, rack of payment should not preclude that as it has in some cases in the past. Protein restriction is still a bit controversial, but most nephrologists advocate some protein restriction, at least early in the course of disease. As the disease progresses we have to be careful, balancing what we hope might improve and reduce the rate of progression of chronic kidney disease and help our patients to feel better, but not have them become malnourished. So this becomes a difficult balancing act, and one needs the assistance of a trained nutritionist.
Team approach: role of primary care physician (PCP) and nephrologist in CKD
I'm going to say a couple more things that lead into the team approach. For 20 million patients with chronic kidney disease, 20 million more at risk. This is a huge effort. If we're going to tackle this, it's going to involve a collaborative approach with primary care providers and nephrology teams. The primary care providers are in the best position to identify and screen at risk patients for chronic kidney disease. They will be the ones providing the ongoing management of patients with chronic kidney disease and need to play an important role in patient education. But the nephrologists and the nephrology team can help tremendously and need to be involved early from the point of helping make diagnoses and assessing the patient's condition and providing strategic guides for the overall management. That's an important role that the nephrologists can play; they can implement further patient care, and the nephrology team can help with patient education and implementation of some of the treatment strategy such as administration of erythropoietin that many primary care provider offices are not equipped to deal with.
Continuum of CKD care: interaction of PCP and nephrologist
So if we look at chronic kidney disease as a progression from stage 1 to stage 5, we have the need for interaction between primary care providers and the nephrology teams working together. At the very latest, the nephrologists need to be involved in stage 3. If there are signs of kidney damage, it may be even earlier, but at least by stage 3. Then as the disease progresses, the nephrologists may assume an ever increasing role, but care will still involve both the primary care providers and nephrologists.
Early kidney disease is receiving more attention
Since I'm approaching my time limit, I think I'd best stop here. What I've tried to go over in my time is to let you know that this is a much common condition than was thought Diabetes, and hypertension are not separate conditions, but kidney disease is part and parcel of the complication of these diseases, but has really not been given enough attention. It's a major factor impacting on cardiovascular mortality in our inpatients and there's a thrust now to try to identify this.
Healthy people 2010 objectives
I didn't have time to go over it, but there's a lot more attention being paid through the federal government from the Surgeon General's Report, - Healthy People 2010 to a National Kidney Education task force; to involvement of the National Kidney Foundation and the pharmaceutical firms.
A major impact for us to ultimately reduce the mortality of our dialysis patients.
It's will to be identifying these patients early on and getting them on the right treatment strategy. Then those that do reach dialysis are going to be in much better shape, and should do better. So let me stop here and thank you very much.
1. No Author Listed. 2000 ADR/Atlas. Incidence & Prevalence. United States Renal Data Systems 2000:41-44.
2. No Author Listed. The Problem of Kidney and Urologic Disease. National Kidney Foundation
3. No Author Listed. Patient Mortality and Survival. United Stated Renal Data Systems 1995: 59-77.
4. Meyer KB, Levey AS. Controlling the epidemic of cardiovascular disease in chronic renal disease: report from the National Kidney Foundation Task Force on cardiovascular disease. J Am Soc Nephrol 1998 Dec;9(12 Suppl):S31-42. No abstract available
5. McCarthy JT. A practical approach to the management of patients with chronic renal failure. Mayo Clin Proc 1999 Mar;74(3):269-73.
6. Obrador GT, et al. Prevalence of and factors associated with suboptimal care before initiation of dialysis in the United States. J Am Soc Nephrol 1999 Aug;10(8):1793-800.
7. No Author Listed. Morbidity and mortality of renal dialysis: an NIH consensus conference statement. Consensus Development Conference Panel. Ann Intern Med 1994 Jul 1;121(1):62-70. No Abstract Available
8. No Author Listed. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. No authors listed, Am J Kidney Dis 2002 Feb;39(2 Suppl 2):S1-246. No Abstract Available
9. No Author Listed. II. Incidence and prevalence of ESRD. Am J Kidney Dis 1999 Aug;34(2 Suppl 1):S40-50. No Abstract Available
10. No Author Listed. Kidney Disease of Diabetics. NIH Publication No. 01-3925 July 1995.
11. Walker WG, et al. Renal function change in hypertensive members of the Multiple Risk Factor Intervention Trial. Racial and treatment effects. The MRFIT Research Group. JAMA 1992 Dec 2;268(21):3085-91.
12. No Author Listed. Standards of medical care for patients with diabetes mellitus. Diabetes Care 2000 Jan;23 Suppl 1:S32-42. No Abstract Avaiable.
13. Klag MJ, et al. Blood pressure and endstage renal disease in men. Klag MJ, et al. N Engl J Med 1996 Jan 4;334(1):13-8.
14. Levin A, et al. Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Levin A, et al. Am J Kidney Dis 1996 Mar;27(3):347-54.
15. Levin A. Identification of patients and risk factors in chronic kidney disease-evaluating risk factors and therapeutic strategies. Nephrol Dial Transplant 2001;16 Suppl 7:57-60. No Abstract Available.
16. Levin A. Prevalence of cardiovascular damage in early renal disease. Nephrol Dial Transplant 2001;16 Suppl 2:7-11.
17. No Author Listed. NKF-DOQI clinical practice guidelines for the treatment of anemia of chronic renal failure. National Kidney Foundation-Dialysis Outcomes Quality Initiative. Am J Kidney Dis. 1997 Oct;30(4 Suppl 3):S192-240. No abstract available.
18.Hayashi T, et al. Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure. Am J Kidney Dis. 2000 Feb;35(2):250-6.
19. Franklin LA, et al. Efficacy and tolerance of treatment with recombinant-human erythropoietin in chronic renal failure (pre-dialysis) patients. Nephrol Dial Transplant. 1989;4(9):782-6.
20. Kulzer P, et al. Effectiveness and safety of recombinant human erythropoietin (r-HuEPO) in the treatment of anemia of chronic renal failure in non dialysis patients. European Multicentre Study Group. Int J Artif Organs. 1994 Apr;17(4):195-202.
21. Kausz AT, et al. Anemia management in patients with chronic renal insufficiency. Am J Kidney Dis. 2000 Dec;36(6 Suppl 3):S39-51.
22. Eknoyan G, et al. The national epidemic of chronic kidney disease. What we know and what we can do. Postgrad Med 2001 Sep;110(3):23-9.
23. No Author Listed. Chronic Kidney Disease. National Institute of Health Chap 4; 1-29.
24. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41.
Next Talk (Ann Compton)
This educational activity is supported by an educational grant from Ortho Biotech Inc.
This activity has been planned and produced in accordance with CE Guidelines and Policies.
This educational activity is based on an official ANNA dinner symposium, but the program was not planned by the ANNA Program Committee.