PREVENTING KIDNEY FAILURE

by Shannon Glowacki, MD

Dr. Glowacki delivered the following as the keynote address at the Diabetes Action Network's July 6 seminar, held as part of the 1998 annual convention of the National Federation of the Blind, in Dallas, Texas.

First of all, thank you very much for inviting me. It's an honor to be here. Somebody said to me, "Remember in any talk give three points." Today, my points are EDUCATION, SCREENING and EARLY INTERVENTION.

I am going to start by telling you a story, one that I hear too often. About every third or fourth patient who comes to our nephrology office has it. Typically, she is a 55-year-old female, most often, in my practice, African-American and obese. She will come to me and say, "Gee, my doctor sent me saying that there is something wrong with my kidneys." She may have had diabetes for 20 years, and hypertension for ten years, coronary artery disease (maybe not a myocardial infarction), but she does have angina. Our typical patient has no significant diabetic ulcers or amputations, but she will have had an ulcer. She'll have early diabetic retinopathy. She'll have seen an ophthalmologist and they'll have done laser intervention.

These patients come with information, sent by the reference physician; a blood test, maybe more... I can tell that they have approximately 25-30% kidney function. I make sure it is in fact diabetic nephropathy (99% of the time it is), as just because you are diabetic doesn't mean you can't have another kidney disease.

On the next visit or two we talk about the fact that I cannot fix their kidney. All we can do, right now, is try to prevent the disease from progressing too quickly. Most often, these people are on dialysis in the next two to three years despite all of our efforts.

When we talk about education, we don't just mean you, the patient, but also the referring physicians and just about everybody else in the population. A lot of what I am going to say actually I never get a chance to implement—but if we are going to make a difference in this disease, the intervention has to be early on, before you ever get to me. Hopefully, you won't have to see me.

First of all, diabetic nephropathy we need to take seriously—not just you, not just me, but our neighbors out there. It is one the most expensive diseases out there, as I am sure you are aware. We are looking at 30-50% suffering from diabetes and not in combination with other diseases. Dialysis and transplantation cost $3 billion in 1994, and a large part was due to diabetes.

In the type 1 diabetic population, approximately 40% will develop a renal insufficiency or disease. However, 60% of the diabetics on dialysis are type 2. It is a huge problem, and we need to go back and look at intervening early, before you even need to see me.

Let's go back into the type 1 information of what we know about nephropathy. "How can I predict if I am going to be one of the 40% who develops kidney disease?" There is no absolute answer to that question, but there are lots of markers, there's a lot of indicators, there's a lot of what we call "risk factors." There is no absolute way that we can predict 100%, but let's talk about some of the interventions.

Genetics certainly are a factor. If you have siblings, if you have family history, if you have a genetic susceptibility, if you have hypertension, then you are at more risk.

Glucose. Glycemic control early on is crucial. By the time you see me, it is likely not going to be a huge factor in the rate of progression of deterioration. Early on it is certainly a factor, as you know with all our other organs.

One other issue is race. There is no question that African-Americans, Mexican-Americans, and Native Americans have increased risk at incidence and prevalence of kidney problems compared to Caucasian diabetics. There is still a genetic susceptibility that we haven't put our finger on.

Let's come back to the kidney. The kidney is a sensor; it filters poisons and it filters fluids. Those are its two main jobs. It is also involved in blood pressure, and it responds to anemia by sending a messenger to the bone marrow to make red blood cells, etc. But the two big things are getting rid of fluids and poisons, the biggest one being poisons. You cannot live without this kidney function.

Dialysis is not a cure; it is only a replacement therapy, replacement for the function of the kidney. Usually we talk about dialysis when kidney function, for whatever reason, gets down to 10%.

The kidney is a filter, it is a big filter. We each have a million little filters called glomeruli in each kidney. In the normal kidney with no disease, by the time you are 80 years old, all those filters are not working 100%. If you look at an old person's kidney under microscope half the filters are scarred up. That is just age, the kidney ages.

Let's go back to the diabetic kidney. Early on, almost all diabetic kidneys are working overtime. Why? I will be honest with you, we don't know why. It is not just insulin, it is not just the glucose, the glucagon, or the hormones. A kidney working overtime is not a good thing because it is going to burn out faster.

Everybody with diabetes has functional changes in the kidney. Every kidney with diabetes undergoes minor changes; that still is not a bad thing. It is when you move on and progress to more serious lesions and scarring in the kidney that things may change. You have a kidney that is working overtime and even if you have great glycemic control and great blood pressure control, and the diet is perfect and we are doing everything we can, every diabetic kidney is going to be working a little bit overtime because there is no such thing as perfect glycemic control.

One of the markers now that we do know, we've known quite a few years, is microalbuminuria. It identifies that we are moving into the target zone. During that microalbuminuria time everything else is looking good, the kidney is still filtering at a 100% and the urine is still a 100 or better. We are starting to see a problem, this is the marker.

I will be honest with you; I have never measured for microalbuminuria. I am a nephrologist and have never measured for microalbuminuria! Why? Because by the time they get to me, patients are past that stage. This is a stage that needs to be done in the family doctor's office; a screening test, identifying the problem. Hopefully this is the time when we need to make that intervention, to make the difference so that it doesn't worsen.

Worsen how? By developing a slow progression of deterioration in the kidney function. You want to prevent that—we've got to stop it—before it gets to that point.

What can we do to make a difference? Best would be preventing diabetes in the first place, but changing the environment of what diabetes is, early on, is number one. Number two is blood pressure. This is a message, diabetic or not, that everyone needs to hear. Hypertension is one of the worst things you can do to your body, diabetic or not. If affects your brain, it affects your heart, and it affects your kidneys. No matter what disease you have, when you come to see me, I rely on that kidney.

High blood pressure is one of the most significant causes for progression of deterioration of renal function. It is usually a very straight line, not the same line in everybody, but usually a very predictable and slow course. Obviously we wanted to find things that would change that slope of that line, flatten it out a bit, make it slower, make it stable. The first thing, still to this day, that can change that line is blood pressure control, just garden variety blood pressure control. What blood pressure control are we aiming for? If you have hypertension, we would be aiming for 140/90, a general recommendation. When too low we are talking 100/60. In the diabetic population, clearly that goal has been readjusted by the hypertensive society and I believe the diabetic society. The hypertensive recommendation is 130/80. I still think that we all, both patients and physicians, fail miserably at reaching that goal, maintaining that goal, and monitoring that goal.

We all need to know our blood pressure. The most important thing is blood pressure control, blood pressure control, blood pressure control. Those studies that show the straightening of the line weren't done with any of that fancy stuff you've all heard about, they were done with very early and simple hypertensive medication.

What about the fancy blood pressure medication? What about the ace-inhibitors? Hopefully anybody with any microalbuminuria should be on an ace-inhibitor. Obviously if you have hypertension and early signs of kidney disease, that ace-inhibitor is the first line drug of choice. Generally speaking, the ace-inhibitor should be the drug of choice.

It also helps to decrease pressure within the kidney. Remember that filter with blood going in and blood going out? Well, guess what happens. There is pressure across there, as with any artery changing into a vein. Any increase in pressure there, a kidney working overtime, or a little filter working overtime, only serves to hasten scarring and deterioration. Lessening the pressure, not only in the blood vessels all over your body, but also specifically in the glomeruli, as the ace-inhibitor does, helps to decrease that protein, and hopefully does decrease the scarring and disease progression.

Lets talk about people who have microalbuminuria. If they have normal blood pressure, should they be on an ace-inhibitor? The answer to that is yes, a careful low dose. If you have normal pressure and are taking an ace-inhibitor, it should not drop your blood pressure significantly. There are some people who have a blood pressure of about 110/60, and who have a little bit of kidney disease, but cannot tolerate a low dose ace-inhibitor, because they seriously do feel light headed and dizzy. But everyone should be tried on it, as generally speaking it is very well tolerated.

To summarize: Ace-inhibitors should be used as a first line in hypertension and diabetes, they should be tried in a low dose in a normal tension person with microalbuminuria, and they should definitely be used in a person with identified renal problems and hypertension, as the first line of therapy.

Next, what about the next group of medications, the calcium channel blockers? Calcium channel blockers work obviously by blocking calcium channels in cells and blood vessels, to help with hypertension. Very effective group of drugs. It's very effective hypertension control—I like that group.

Let's go back a minute. We talked about glycemic control, blood pressure control in general, then the choice of blood pressure control, ace-inhibitors, and calcium channel blockers. As we may or may not know, some of the side effects of those blood pressure medications have to be considered. One of those side effects concerns lipids.

Let's go to lipids. Lipids are hard on the kidney, diabetes or not, but it has been shown in diabetes that lipids are especially dangerous. High cholesterol, bad for your heart and brain, is also bad for your kidneys, too. It makes the scarring, the thickening, and the loss of efficiency happen faster. There is no question that you need to be attentive to your cholesterol and to the medication that are required to take care of your cholesterol and triglycerides. Not only for your diabetes, but for your heart, brain and your kidneys.

The other thing is diet. Is there a perfect diet in this world? NO! I think that we should all live on fresh fruit and vegetables, and fish and chicken. Wouldn't that be fun?! There is no such thing as a perfect diet for anybody, I think. Added to the mix of everything else you have to deal with is protein. How many people here have a protein restricted diet?! That must be hard balancing all the carbohydrates and everything else.

Let's go over the protein studies for just a minute. Protein is a tough one. Those initial studies on protein restriction, from Italy, were not just done on diabetics; diabetics were in the mix, but so were chronically ill from all other issues. There were people with established, not just early, kidney disease, and researchers found out that by restricting the protein you can make a difference in the pressure of renal disease. We know now that the pressure on the filters, produced by higher protein diet can be decreased by a low protein diet. Just by some decrease in protein consumption, you decrease the work of that filter, and you are protecting your kidneys.

We know the other side pushing that restriction is malnourishment. Protein restriction can help decrease those poisons your kidneys filled up, but if you go into needing dialysis, one thing we discovered is not to go in malnourished. There are a lot of controversies about protein restriction, but common sense is not to protein overload on a regular basis.

We've already had a disease that is affecting the process, and we are trying to make broad flashes at intervention of that process. There are studies coming more specifically at the diabetic intervention with glucose and metabolism, and their results hopefully will make some big differences down the road. I think they are getting closer with those interventions, but they are going to be more specific to diabetes. The good news is that there is no question these interventions can make a difference.

That story I told you at the beginning should not be happening—not without a long fight. What I find so interesting is the people who come to me know nothing about it, have no sense of where they are. There is no question that we need early intervention and teaching, this goes back to the patient being informed, the internists being informed, and certainly the endocrinologist. I think we all really need to be on board, you need to know your screening, you need to know what you are looking for.