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Dr. Anton Schoolwerth:
Good evening. My name is Anton Schoolwerth and it's my pleasure to welcome you to the symposium this evening, "The Advancement of Clinical Practice in Chronic Kidney Disease." We have a distinguished panel here whom I'd like to introduce to you. We have Dr. William McClellan from Emory University School of Medicine. He is also the Medical Director of Health Services Research at the Georgia Medical Care Foundation in Atlanta. Dr. Patrick Parfrey is a University Research Professor at Memorial University of Newfoundland in Canada. We have Dr. Amin Al-Ahmad who is a cardiologist from Tufts University in Boston. And subbing for Dr. Ajay Singh, whose wife is about to or may have already delivered her child, Dr. Donal Reddan, Associate in Medicine at Duke University. Dr. Reddan is also the Co-PI for the CHOIR study, which you'll hear more about from him this evening. I'd like now to introduce the Co-moderator of the program, Dr. Kline Bolton, who's Professor and Chief of the Division of Nephrology at the University of Virginia in Charlottesville.

Dr. Kline Bolton: Thank you, Anton. And I'd like to extend my welcome as well to all of you for being here. We have an interesting program that I think is addressing a very pivotal area. I have some housekeeping things that I need to take care of first. First of all, I would like to thank Ortho Biotech for the educational grant that's made it possible for us to get together and to discuss the advancement of clinical practice in chronic kidney disease.

We're going to have a short question and answer session after each one of the presentations and then there will be a panel discussion with all of us taking questions. Dr. Parfrey has agreed to take all of the questions that nobody else can answer. And if you do have questions please indicate them on your cards that you have, hand those out and then they will be collected. We will not answer questions that we cannot read.

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Introduction
So now I would like to go ahead with the program. My task in the next couple of minutes is an introduction. And I wanted to point out a couple of things that may be self-evident but I think are extremely important.

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Life expectancy for selected diseases
The first of these is that nephrologists and primary care physicians and the public alike think of dialysis as a life-saving therapeutic modality, which it is indeed. But while it's life-saving, it is not a panacea. This is looking at life expectancy of selected diseases at patients aged 49 and 59. This is the remaining years.

In yellow is the average United States life expectancy. Prostate cancer is in blue. Colon cancer is in red. Lung cancer is in light blue. And you will see that even though we do indeed save patients from dying by putting them on some form of renal replacement therapy that the overall outcomes are worse than any type of cancer other than lung cancer. So we have a long way to go.

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Source: Meyer KB et al, J Am Soc Nephrol. 1998 Dec;9(12 Suppl):S31-42. No abstract available.

Cardiovascular disease
A major part of this process and the morbidity and the mortality associated with chronic kidney disease and with end stage renal disease is cardiovascular disease. And that's the major killer. And we will be addressing that in multiple lectures that follow this. This is a slide which was adapted from Meyer and Levey. It shows the age in years of the United States general population here in yellow and in green the dialysis population. This is a logarithmic scale here. And so there's approximately a 100-fold difference in the mortality rate in young people, which begins to approach the same point as they get older. What this means is that the cardiovascular mortality of a 25-or a 30-year-old person on dialysis with end stage renal disease is the same as about a 70-or a 75-year-old person. This is certainly of grave concern.

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Source: National Kidney Foundation, Am J Kidney Dis. 2002 Feb;39(2 Suppl 2):S1-246. No abstract available.

Stages of chronic kidney disease and recommended clinical action
Recently, the National Kidney Foundation has put together a work group headed by Andy Levey and a number of us have participated in that. And it has been to define chronic kidney disease and to give us a starting place for intervening in the ravages of that disease. Part of what came out of that was a staging of chronic kidney disease and recommendations for clinical action. The stages are listed, a description of the stages, the GFR which is an estimated GFR from either an MDRD or a Cockcroft-Gault. And then the action that is suggested. I'm not going to address the action. I would point out there is no stage zero for CKD. That's my own designation, because these are patients that are at increased risk. They have a GFR which is normal but they have some underlying risk factors for chronic kidney disease such as diabetes or hypertension or a family history or single kidney or what have you.

Stage one are those patients with normal kidney function but with some evidence of kidney damage. Either they've had previous kidney damage or they may have proteinuria. Stage two is mild decrease in glomerular filtration rate, 60 to 89ml/min/1.73m2. This is the range that is frequently missed but this is where things begin to happen. The data that's presented from the CKD Clinical Practice Guidelines shows that at 60 this is where hyperparathyroidism begins to occur, bone disease, anemia and the ravages of end stage renal disease begin to appear at this phase. This is when testing should be done and screening for the anemia of renal disease and hyperparathyroidism which most physicians don't realize is occurring at this point.

Stage three is moderate decrease in GFR, 30 to 59. Stage four is a severe decrease in GFR, 15 to 29. And stage five is kidney failure less than 15, followed then by renal replacement therapy. The current clinical practice guideline work committee for appropriate preparation for renal replacement therapy is addressing this and there will be a talk later in the symposium describing the evidence as it is for this group of patients and the recommendations for intervention.

One of the major things that has occurred because of that is a realization that chronic kidney disease is an epidemic and worse than that it's a hidden epidemic. We're used to dealing with stage five. We now, like the cancer folks and everybody else, have a staging, Stage five is our patients that are getting ready to go on dialysis or are on dialysis.

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Stages and prevalence of chronic kidney disease
This is how many there are looking in prevalence times 1,000. These are patients with clearances or GFRs between 15 and 29. Ninety percent of these patients are going to progress to stage five and require renal replacement therapy. But this is the tip of the iceberg. Here we are at stage three, two and one and the total of these five stages makes up approximately 20 million people. Most of stage one and two are not detected. Even more alarming is that there's an additional 20 million people who have some type of risk factor. We have no idea how many of this group will progress to one or two or to three. But we do know that when they reach this point it's downhill for the majority of the patients.

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Healthy People 2010
It's also obvious that there needs to be some intervention earlier. And the alarming societal and financial cost of this has led to inclusion in Healthy People 2010 by Surgeon General Satcher of the first chapter on kidney diseases. The objective is to reduce the incidence, the morbidity, mortality and health costs of chronic kidney disease by increasing screening, by increasing counseling for risk factors, treatment of underlying diseases such as diabetes and hypertension that are major causes of chronic kidney disease.

Chronic kidney disease doesn't start when the patient gets on dialysis. And the complications of end stage renal disease don't start when the patient gets on dialysis. It occurs much sooner. And the current National Kidney Foundation work groups addressed at many different areas are looking at trying to impact this early relationship because this is where the changes are going to occur that have a beneficial effect for patients on dialysis.

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Kidney care recommendations
This is a diagram that I've put together that's going to be coming out in Postgraduate Medicine, Kidney Care Recommendation. And it sort of in cartoon form represents the primary care physician and the amount of input that they have with the patient with chronic kidney disease. Most of those referrals occur for a specific reason such as proteinuria or hematuria. But actually as you go down through here there's a need for more and more intervention and more and more interaction between the nephrologists or for the nephrology team in taking care of these patients in preparation for renal replacement therapy.

And the complications that we're going to talk about today and the problems that are going to be addressed are up in here and we have to intervene at a much earlier stage. And the speakers that follow me that are going to provide you with information regarding their areas; they are going to give you evidence that this is where things are happening. I'm going to give you some ideas about what the rationale is for intervention that we can take. They'll also point out to you that there's a need for additional studies to provide the evidence that's necessary for us to go forward and make the intervention that will end up helping our patients and improving our outcomes for these patients.


References

1. 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.

2. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis. 2002 Feb;39(2 Suppl 2):S1-246. No abstract available.