How to Preserve the Life of Your Diabetic Kidneys
Kidneys You Can Avoid Dialysis And Transplantation
by Steven V. Edelman, M.D.
Introduction
Diabetic kidney disease is a scary thing. To think about being on dialysis or needing a cadaver or living donor transplantation is depressing. Unfortunately, diabetic kidney disease causes a tremendous amount of grief and misery for people with diabetes. Diabetes is one of the leading causes of kidney failure in the world and soaks up a large part of the health care dollar. I remember quite clearly when I studied physiology during medical school in 1978 at the University of California Davis campus. The professor was citing statistics from very old textbooks about the high death rate in people with diabetes. He stated that 50% of people with diabetes die from diabetic kidney disease within 20 years after the initial diagnosis of diabetes. All of my classmates were looking directly at me to see my expression, or to give me some type of visual sympathy. That afternoon we had physiology laboratory and I had to dissect the cadaver of a 25 year old male who died from diabetic kidney disease. At the time I was 23 years old with 8 years of diabetes behind me. I told myself that I would at least do everything in my power to prevent the development and progression of kidney disease. In 1982, while I was training to be a diabetes specialist at the Joslin Diabetic Clinic in Boston, I discovered that my blood pressure was elevated for the first time and I did not want to take a drug. To me it was a sign of weakness and vulnerability. The only medications that I regularly took up to this during my entire life was just insulin. This period in my diabetic life was emotionally significant for me because it marked the first time that I needed medication for a complication of diabetes. Even though I already had retinopathy, I did not need daily drugs after I received laser treatments. I finally slapped my self around and said to myself...who are you fooling and what are you accomplishing by avoiding an important therapeutic modality to preserve the life of your kidneys.
The message I have for you in this chapter is: DIABETIC KIDNEY DISEASE IS PREVENTABLE AND TREATABLE. Through years of clinical research, we now know of several techniques to prevent the onset and delay the progression of diabetic kidney disease. In addition to aggressively treating kidney disease, screening methods to diagnosis this problem early have been developed. This information is vital to all people with diabetes to avoid end stage kidney disease (dialysis or transplantation).
Definition
What is diabetic kidney disease and why do diabetics get kidney disease? Stating it very simply, diabetic kidney disease is the failure of the kidneys to function properly due to poorly controlled blood sugars and blood pressure over an extended period of time. Diabetic kidney disease is also referred to as diabetic nephropathy in the medical literature. The kidneys are very important and vital organs responsible for filtering and cleaning our blood. The kidneys are also responsible for maintaining electrolyte balance (sodium, potassium, chlorine, carbon dioxide, etc.) and normal fluid levels in our bodies. Years of chronically elevated blood sugars damage the vital filtering structures of the kidneys in a similar fashion to what is seen in the eyes and nerves. Poorly controlled blood pressure, which can be a early manifestation of kidney disease or be present because it runs in your family, is also very damaging to the kidneys. High blood pressure will greatly accelerate the decline of kidney function if untreated inadequate screening for the early signs of diabetic kidney disease, and thus delaying proper treatment, is also a serious problem. Very sensitive tests are now available that can detect kidney disease at a very early state where the damage may be reversible with aggressive treatment. The information and advise in this chapter is simple, straightforward, and relatively easy to follow, yet it is also vitally important to preserve the life of your diabetic kidneys. Just... do it! Prevention Glucose Control: Prevention of diabetic kidney disease by maintaining tight glucose control has been proven convincingly by the Diabetes Control and Complications Trial (DCCT) discussed earlier. The DCCT conclusively demonstrated the importance of glucose control in preventing the onset and delaying the progression of the classic microvascular complications of diabetes (eye, kidney, and nerve disease ), in patients with type 1 diabetes. The DCCT was not the first study to demonstrate the importance of glucose control, although it has set the standard of care for glycemic control in the United States and around the world. The importance of glucose control in patients with type 2 diabetes is now widely accepted by physicians as it is with type 1 diabetes. The majority of diabetes specialists, and other care givers who are interested in diabetes, feel that the duration and severity of hyperglycemia will dictate the rate and extent of microvascular complications, such as kidney disease, in all patients with diabetes no matter what type of diabetes is present.
Early Detection
Diabetic kidney disease has a natural history, in a similar manner to what is seen in type 2 diabetes, in that it takes years to develop and deteriorate to an end stage situation. The big problem is that in the very early stages, when aggressive therapy can prevent the progression of diabetic kidney disease, there are no symptoms that can be recognized. If you or your doctor are unaware of the screening methods to pick up early problems, then by the time you feel poorly from the late stages of kidney disease, you would have missed a golden opportunity to catch things early and prevent progression of this potentially devastating complication.
Microalbuminuria: The first measurable laboratory abnormality very early in the course of diabetic kidney disease is the presence of albumin in the urine in very small amounts, which is refereed to as microalbuminuria. Albumin is a protein that is normally not found in the urine. The word micro refers to a small amount of albumin in the urine and not an abnormally small sized protein. People with microaluminuria have a high likelihood of experiencing decreasing kidney function over a period of years if left untreated. The important thing to remember is that once microalbuminuria is present, there are therapeutic maneuvers to retard the progression of diabetic kidney disease. This is why screening is so important, so that aggressive management, which will be discussed later, can be started in a timely fashion. You are responsible for getting tested for the presence of microalbuminuria and getting aggressive therapy if needed. This test for microalbuminuria was not available until only a few years ago. I will always remember the day when I got a call from a representative from an insurance company that I was seeking to get life insurance from. He said Dr. Edelman... I regret to inform you that your application for life insurance was denied because the urine sample we received from you had several thousand milligrams of albumin in it. I was shocked because I knew this was an indication of fairly advanced kidney disease, way past the microalbuminia stage. This was a huge wake up call for me. If you have type 1 diabetes, you should be screened for microalbuminuria once a year starting after 5 years from the time of your diagnosis of diabetes. People with type 2 diabetes should be screened every year from the time of diagnosis, since it usually takes several years to diagnose the average person with type 2 diabetes. There are several different screening tests for microalbuminia, which usually involves a timed urine collection (12 or 24 hours) for albumin. Your physician can also measure a ratio of the albumin in the urine to the creatinine (another substance that goes up with kidney disease) in the blood (table 2). The purpose of showing you table 2 is not for you to completely understand or memorize all of the medical jargon, but to be aware of the different ways that your kidney function can be evaluated.
Table 2: Definitions of Urinary Albumin Excretion Rates
(AER) urinary AER urinary AER urinary albumin (mg)
(mg/day) (ug/min) to creatinine (G) ratio
Normoalbuminuria <30 <20 <30
Micralbuminuria 30-300 20-200 30-300
Macroalbuminuria >300 >200 >300
You can also be screened with a very simple and quick urine dip test strip that measures microalbuminuria in the urine (Micral test strips made by Roche/Boehringer Mannheim). This test strip is much different than the older strips that have around for a long time and test only for gross protein or macroalbuminuria, and not microalbuminuria. This older method is too insensitive to pick up small amounts of albumin or protein. If the Micral test is negative then you can be re-screened again in one year. However if the screening test is positive or even marginally positive, then I recommend getting a 24 hour collection. Certain situations, such as strenuous exercise, may make your microalbumin test positive even though you do not have diabetic kidney disease. Hence, confirming the presence of microalbuminuria with at least one more additional test is suggested, especially before starting aggressive therapy.
I also feel it is very important to repeat yearly microalbuminuria testing, even if you are being treated aggressively. If the microalbumin level is continuing to increase despite aggressive therapy, then that would warrant a closer look by your physician for additional factors that would hasten the decline of your kidneys. Some of these factors include making sure that your blood pressure control over a 24 hour period is adequate with a special computerized monitoring device and examining any other medications that you are on they may damage the kidneys. If your doctor has already told you that you have evidence of excessive protein in your urine (another way of saying macroalbuminuria or much more than a little protein in your urine), then you are past the microalbuminuria stage. You now need to have regular urine tests to measure how much protein or albumin is in your urine and receive aggressive therapy to retard the progression. It is also extremely important to realize the presence of microalbuminuria or protein in the urine may be a marker for additional abnormalities other than the development of end stage kidney disease. Microalbuminuria is also associated with the presence of diabetic retinopathy or eye disease, high cholesterol levels, and heart disease. The presence of microalbuminuria should alert you and your care giver to consider that some of these other abnormalities may be present. Blood pressure screening: Proper blood pressure screening is also a very important tool in picking up early kidney disease. If you are at risk for the development of kidney disease, then I suggest an accurate home blood pressure monitoring device so that you can take your own readings on a regular basis. It is usually much more accurate to measure your blood pressure at home during your normal daily activities, and not in a doctors office. Home blood pressure monitory allows for a much more accurate indication of what your blood pressure values are on the average. Home blood pressure monitoring devices are very inexpensive and can be found at most pharmacies, department stores, or medical supply stores. Pick out one that you feel comfortable using and has a good warranty. It is important to bring your home blood pressure device to your doctors office once or twice a year so that one of the staff can compare the readings on your machine to the gold standard method of manually pumping up the sphygmomanometer and listening to the pulses in your arm, come and go, with a stethoscope. If the values are not within 10% of each other, then you need to get your machine calibrated. It may also be possible that the office staff person who took your readings did not know the proper technique to measure blood pressure, which is not uncommon.
Aggressive Management
Diabetic kidney disease is treatable. You can truly make a difference in your risk of developing end stage renal disease requiring dialysis or transplantation. Four therapeutic strategies have been well proven to prevent the progression of diabetic kidney disease (glucose control, blood pressure control, use of ACE inhibitors, and a low protein meal plan). Two other strategies have not been well proven (cholesterol eduction and antioxidants), however may be of therapeutic benefit and will be discussed (table 3)
Table 3: Therapeutic Strategies to Prevent or Retard the Progression of Diabetic Kidney Disease
Proven Therapeutic Interventions
1. Glucose Control
2. Blood Pressure Control
3. Use of ACE inhibitors
4. Low Protein Meal Plan
Unproven Therapeutic Interventions
5. Cholesterol lowering (esp. LDL cholesterol)
6. Antioxidants
1. Glucose Control: As discussed above, the DCCT study conclusively demonstrated that intensive glucose control can retard the progression of diabetic kidney disease, once already present in individuals with diabetes. It does not matter if you have type 1 or type 2 diabetes, glucose control is crucial and you must use the suggestions throughout this book, with the help of your doctor, to achieve the best control that is possible for you. Get that glycosylated hemoglobin or fructosamine value in a near normal desirable range.
2. Blood Pressure Control: Aggressive blood pressure control, along with glucose control, is probably one of the most powerful interventions to reduce the progression of diabetic kidney disease. Every person with high blood pressure or hypertension should have a home blood pressure monitoring device, just as every person with diabetes should have a home glucose monitoring device. The treatment of diabetic hypertension is the topic of an entire book, however it deserves of few comments here and will be discussed further in the next chapter. First of all, it is important that normal blood pressure is defined correctly. Blood pressure goals have been defined differently and have been recently changed by several organizations (World Health organization, American Heart Association, American Diabetes Association, etc.). The American Diabetes Association currently recommends treatment to at least less than 130/85 mmHg if there is no evidence of protein or albumin in the urine. If you have evidence of protein or albumin in your urine, then your average blood pressure should be less than 120/80 mm/Hg (table 4).
Table 4
Goals for Blood Pressure Control
No Evidence Of Protein Or Albumin In The Urine
1. Systolic Blood Pressure less than or equal to 130 mm/Hg
2. Diastolic Blood Pressure less than or equal to 85 mm/Hg
Medical Jargon: ( 130/85mm/Hg
People With Persistent Protein Or Albumin In The Urine
1. Systolic Blood Pressure less than or equal to 120 mm/Hg
2. Diastolic Blood pressure less than or equal to 80 mm/hg
Medical Jargon: (120/80mmHg
The top number in a blood pressure reading refers to the systolic blood pressure and represents the pressure when the heart is working its hardest to pump out blood to the rest of the vital organs of the body. The bottom number refers to the diastolic blood pressure and represents the pressure when the heart is resting, filling up with blood before the next systolic beat. The abbreviation, mm/Hg, refers to millimeters of mercury which is the universal unit of measuring blood pressure. When your blood pressure is too high, it puts a very large strain not only on your heart and blood vessels, but also your kidneys, brain, and eyes. Elevated blood pressure over the years leads to heart attacks, strokes, and accelerated eye and kidney disease.
3. Use of ACE Inhibitors: Angiotensin Converting Enzyme (ACE) inhibitors represent an entire class of blood pressure lowering medications. ACE inhibitors have proven very effective at preventing and slowing down the progression of diabetic kidney disease in terms of reducing albumin (protein) spillage into the urine and lowering blood pressure. ACE inhibitors have also been shown to benefit the kidneys of type 1 and type 2 diabetics who have microalbuminuria, even when the blood pressure is normal. In this scenario, ACE inhibitors are given in low doses so that the blood pressure does not get too low. In summary, ACE inhibitors protect the kidneys from further decline in function. You need to know if you are a candidate for taking an ACE inhibitor. Table 5 lists some commonly used ACE inhibitors available.
Table 5
ACE Inhibitors Available For Prescription
1. Accupril (Parke-Davis)
2. Vasotec (Merck)
3. Prinivil (Merck)
4. Monopril (Bristol-Myers Squibb)
5. Capoten (Bristol-Myers Squibb)
6. Lotensin (Novartis)
7. Lotrel (Novartis)
8. Univasc (Schwarz)
9. Mavik (Knoll)
10. Zestril (Zeneca)
11. Altace (Hoechst Marion Roussel)
An ACE inhibitor is generally considered the first drug of choice for the hypertension of diabetes, but should be used with caution in two situations. The first is in people who have a tendency to have high potassium levels in the blood. This usually occurs in people who have had diabetes for a long time and they already have some damage to the kidneys. The second situation where ACE inhibitors should be used with caution is a condition called Renal Artery Stenosis . Renal artery stenosis basically means clogging (stenosis) of the arteries that deliver blood to the Kidneys (renal is another medical word for kidneys). How do you know if you have one of these two conditions? It is easy to find out if you have a tendency for high potassium levels in your blood. Potassium levels are very commonly measured in most laboratory blood screens and you should have several measurements in your medical chart. If not, then you can get a simple blood test for potassium that does not require fasting. The symbol for potassium which may be on your laboratory report is K+. Renal artery stenosis is more difficult to detect although it is not too common. Usually if you have stenosis or clogging of your renal or kidney arteries, then you most likely would also have problems with other arteries in your body such as your coronary (heart), cerebro (brain), and lower extremity arteries. If you have any concerns or questions, simply ask your doctor about these issues. If for any reason you are not able to take an ACE inhibitor, then there is a relatively new class of medications, that you may be able to take, that may prove to be just as protective to your kidneys. They are called Angiotension Receptor blockers (ARBs). Cozar (Merck) and Avapro(Bristol-Myers Squibb), and ______(Astra) are Angiotension Receptor blockers. The bottom line is that all diabetics, with few exceptions, should be taking an ACE inhibitor if there is microalbumin or protein in the urine and/or if the blood pressure is high. Even if your blood pressure is normal, and you have microalbuminuria, you should still be taking an ACE inhibitor.
4. Low Protein Meal Plan: Diets high in protein have been shown to induce and accelerate kidney disease in animal and human studies. It is recommended, based on the results of several clinical trials that people with diabetic kidney disease should restrict their protein intake to 0.8 grams per kilogram body weight per day or about 10% of their daily calories. I tell my patients that this is the equivalent to a small or medium amount of protein only once a day. There is also additional evidence that vegetable protein, such as beans and tofu, may be better than animal protein, and that white meat may be better than red meat. This may relate to the fact that red meat has more fat in it than other sources of protein. If you are a steak and potatoes type of eater, you should start thinking about reducing the amount of meat in diet, even long before any evidence of diabetic kidney disease is present. Big changes in life style must come slowly. I grew up eating meat at least two times a day. My family always had some type of red meat or chicken for dinner. My lunches usually consisted of a peanut butter and diet jelly or cold cut sandwich. In addition, I not uncommonly had eggs for breakfast. This type of diet is at least 1.2 grams per kilogram body weight per day or about 20% of my daily calories. I have now slowly adapted to a low protein diet that I enjoy. I usually now have toast or a bagel for breakfast, a veggie or white meat (chicken or tuna) sandwich for lunch and a pasta dish for dinner. If I have a veggie lunch then I would have some protein with dinner. Occasionally I have days where I eat a lot of protein and other days none at all. Trust me...I do not turn down a huge slab of roast beef with creamy horseradish sauce at a banquet dinner for a vegetarian plate. The key is moderation in the diet and to allow yourself to enjoy what you eat so that sticking to your diet comes natural and is not a daily emotional fight or guilt ridden process. Please refer to the chapter on meal planning for more details.
5. Cholesterol reduction: Although not as well proven as the above therapeutic strategies to aggressively treat diabetic kidney disease, there is accumulating evidence that by lowering the cholesterol levels, especially the LDL (low density lipoprotein) or bad cholesterol level, the progression of kidney disease is reduced. The most effective class of medications to reduce your LDL cholesterol level is the statins. The statins are easy to take (once a day usually at bedtime) and have little or no side effects (table 6).
Table 6
Statin Medications Available For Prescription
1. Lipitor or atorvastatin (Parke-Davis)
2. Provachol or pravastatin (Bristol-Myers Squibb)
3. Baycol or cerivastatin (Bayer)
4. Zocor or simvastatin (Merck)
5. Mevacor or lovastatin (Merck)
6. Lescol or fluvastatin (Novartis)
In my opinion, reduction of the LDL cholesterol has been strongly proven to reduce heart disease in people with diabetes, and can only be beneficial. If it turns out that one can also reduce the decline of kidney function by lowering cholesterol levels, then I would have done myself and my patients an extra service. I do not recommend taking any cholesterol lowering medication if your LDL cholesterol level in normal. Normal cholesterol levels are discussed in detail in the chapter entitled, Trust Me...You Do Not Want To Have A Heart Attack.
6. Antioxidants: The role of antioxidants in the treatment of diabetic kidney disease and other microvascular complications is unclear. Many of the studies that have shown benefits of antioxidants are from test tube and animal studies. There is also a body of literature hinting that antioxidants may have benefits on heart disease by improving the character of cholesterol particles so they do not cause heart disease as aggressively. I personally do not push vitamins to my patients, although if they ask me for permission to take antioxidants or for my advice regarding vitamins, I usually suggest vitamins C and E. I know of no adverse effects from taking 800 to 1200 international units (IU) of vitamin E and/or from taking 1000 to 2000 mgs of Vitamin C per day. When purchased at discount stores in larger quantities, vitamins C and E can be fairly inexpensive.
Case Presentation
D.W. 24 year old female diagnosed with type 1 diabetes at age 12. She is currently on a twice daily schedule of NPH insulin and regular insulin. She checks her blood sugars sporadically when she feels high, with most of the morning blood sugars greater than 180 mg/dl. Her last dilated eye exam was 2 months ago and showed early diabetic retinopathy or eye disease. She reports that both feet are a little numb and tingle at night. She continues to exercise regularly running 10-15 miles/week and is at her ideal body weight. She is following a high protein diet that she read about in a sports magazine several years ago. She does not smoke. Over the course of the last year her blood pressure has risen from a baseline of 110/70 to 135/80. A urinary albumin: creatinine ratio measured 4 months ago was 50 mg/g (normal range < 30, see table 2). She takes no medications other than insulin.
Discussion
This woman is a poorly controlled type 1 diabetic who is at significant risk for the development of end stage diabetic disease. She has microalbuminuria, which is the first clinical sign of diabetic kidney disease and her blood pressure is elevated compared to her usual baseline. In addition, her glucose control is not adequate. Treatment of this patients early diabetic kidney disease requires a multifaceted approach including improved glucose control, dietary changes such as reduced daily protein intake and aggressive treatment of her high blood pressure with an ACE inhibitor. She agreed to test her blood sugars more regularly and go on a multiple injection insulin regimen, low protein diet, and start an ACE inhibitor. One year later the albumin in her urine decreased into the normal non-diabetic range.
Summary
DIABETIC KIDNEY DISEASE IS PREVENTABLE AND TREATABLE. The most powerful and proven method of preventing diabetic kidney disease is to maintain strict glycemic control from the time of diagnosis. Early detection is of vital importance in order to initiate aggressive treatment early. Yearly microalbuminuria testing is currently the most sensitive technique to pick up early kidney damage, and it is also a marker for other conditions including heart disease. Once the presence of microalbumin and/or high blood pressure has been detected, aggressive therapy with a number of proven strategies should be instituted as soon as possible. These strategies include glucose control, blood pressure control, use of ACE inhibitors, and a low protein meal plan. Two additional, but not as well proven therapies, include lowering cholesterol levels, and the use of antioxidants. You CAN make a difference in your life and the life of your diabetic kidneys. You CAN prevent the need for dialysis or transplantation.
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