Benjamin Franklin wrote that an “ounce of prevention is worth a pound of cure.” This adage is certainly true with kidney failure. In chapter 3 we learned that the major causes of kidney failure—diabetes and hypertension—can be prevented. Even an inherited disease like polycystic kidney disease (PKD) has environmental and lifestyle components, where interventions can sometimes extend kidney function, indefinitely in some cases. Who would not want to prevent their kidneys from failing? Certainly, few of us would intentionally live our lives in a way that might cause kidney failure. Many otherwise rational people, however, find it hard to do what is best for their health rather than what they are used to doing—or what they would prefer to do. Beyond human nature, there are several other factors that might circumvent early interventions that might prevent or delay kidney failure.
One of them is not knowing that you are sick. When we are young and healthy, it’s easy to neglect our health. Most young people have no medical problems they know about, even though they may be vaguely aware of some that may lurk in the background. That was true for me in my late twenties. After I earned my doctorate, I pursued a research career as a visiting fellow at the National Institutes of Health. My fellowship did not provide health insurance, and I could not afford to buy it. Because I was healthy at the time and did not know I had PKD, I took the chance of doing without health insurance for my two-year fellowship. As a young man I thought I was invincible—that is, until I developed hypertension in my thirties. Even then, I took prescribed medications and went on with my life.
Even when the warning signs of impending disease appear, it can still be difficult to believe that we may eventually face a serious health condition like kidney failure. Denial may prevent us from taking immediate action for our medical condition, especially if we assume that the condition is not serious or that we have plenty of time to address it (see chapter 1). Most people would prefer to focus their attention on more immediate issues. Often it takes a medical crisis to wake us up.
If we accept that we are at risk of a serious medical problem, shouldn’t we want to confront it? Not necessarily, because confronting medical conditions is difficult. Nevertheless, the first step in preventing more serious complications down the road is to reach the stage where we accept that acting now could save our lives.
We understand enough about the risk factors for kidney failure that we know some things we can do to significantly reduce the chances of kidney failure before it occurs. Being educated about health risks is a good start (see chapter 3). In this chapter I outline some specific ways to address these risks. Sound medical practices may reduce the risk of kidney failure and address many other health issues, like the harmful consequences of diabetes, hypertension, and heart disease. In addition to safeguarding your health on your own, you and everyone else need to have regular medical checkups and treatment for any underlying causes of kidney failure.
Hypertension is one of the main contributors to kidney failure, no matter what the primary cause of kidney decline. Although factors related to diabetes, glomerular diseases, and PKD can destroy kidney function, hypertension can accelerate the decline. A major contributor to hypertension is obesity.
Obesity can increase blood pressure in several ways. For one, the heart must work harder to move blood through a large body. In addition, the renin-angiotensin and adrenaline systems become overactive (see chapter 2). In people with diabetes, insulin resistance is a factor. Fat deposits can apply pressure on the outside walls of blood vessels, increasing resistance to blood flow. Finally, increased salt consumption accompanies overeating; excess salt intake promotes water retention, further contributing to hypertension. The bottom line? Overweight people at risk of kidney failure must lose weight.
Granted, losing weight is easier said than done. Books and magazines tout various ways to shed unwanted pounds, and I am not going to evaluate their claims. I will confirm the mantra of every weight-reducing diet, however: to lose weight, you must burn more calories than you consume. This means adopting a healthy, low-calorie, low-fat diet and an exercise program.
I was once obese. In my early forties, I became too fond of junk food. Over time, I gained 60 to 70 pounds above my ideal weight. I had a poor self-image, but what got my attention was an incident one evening as I climbed a flight of stairs to bed. I felt so winded that I could barely breathe. I realized then that if I did not do something about my weight, I might not make it to my sixties.
In consultation with my physician, I changed my diet and started exercising. Changing my diet took time. My body had become accustomed to all the sugar and fat that I had been eating. Eventually my new diet stuck, and I reached a point where eating junk food made me sick. Sticking to my diet didn’t mean I had to deprive myself of anything. When I had a craving for a certain food, I would let myself eat it, but only very small portions. Allowing myself this luxury helped me avoid consuming extra calories.
Beginning an exercise regimen was also a challenge, largely because I did not know how to do it effectively. So I hired a personal trainer who accepted no excuses from me about not coming to the gym as scheduled. The first few months were very frustrating. I did not lose any weight at all for three months, even though I ate a low-calorie diet and vigorously exercised. It took that long to trick my body into accepting my lower caloric intake instead of my usual high caloric consumption. After that, I lost 30 pounds in a few months. Eventually, I lost the extra pounds and returned to a normal weight.
I know firsthand how difficult it is to lose weight. There are no quick tricks, either. To lose weight and keep it off requires a permanent change in lifestyle, involving diet and exercise. You must make losing weight a priority and you must be motivated, disciplined, and determined to get to a healthy weight. With the help of your doctor, a nutritionist, perhaps a personal trainer, and the support of friends and family, you, too, can lose weight. It takes a long-term commitment and patience.
Reducing your intake of specific foods may help you lose weight and may also reduce the strain on your kidneys and prolong their function.
The first dietary change that people with kidney disease should make is to restrict salt intake. Most nutritionists recommend that you ingest no more than 2,000 to 2,400 mg of salt each day from all sources. But so much of what we buy and eat is loaded with salt that salt can be difficult to avoid. Eating less salt can be hard to get used to. Like eating fewer calories, you can condition yourself to prefer the taste of foods with less salt. The biggest culprits providing excess salt are meals in restaurants and prepared foods.
Restaurants often serve extremely large portions of food. Restaurant meals are also often excessively salty. While you shouldn’t avoid eating in restaurants, there are ways you can minimize your caloric and salt intake. First, if your meal is too large, divide it in half or in thirds and take the rest home for subsequent meals. Avoid ordering menu items that come with sauces, which are often full of fat and salt. You may also ask the chef to avoid salting your food as much as possible. (You can always add some salt to taste if the food is too bland.) Eat grilled or broiled food instead of fried food, which is generally high in fat. (If the grilled or broiled food is coated with fat and salt, however, it may still be unhealthy.) Finally, experiment with healthy cuisines that you may not normally eat. You may discover foods that you really like and that are more nutritious and less salty than your normal fare.
Prepared foods often have too much salt. This is especially true of frozen meals and canned foods and soups. You don’t need to avoid these convenience foods completely, but learn how to read the nutrition labels. If you normally eat three meals a day, remember that a single meal cannot contain more than 670 mg of salt and still remain within the daily guideline. Of course, if you eat more than three meals a day—a practice that is often recommended in dieting—each small meal must have proportionally less salt. Several companies, like Healthy Choice and Lean Cuisine, sell frozen meals with lower salt content than other companies’ products. Read and compare labels. Canned foods often have a lot of salt, but you can significantly reduce the salt count by discarding any liquid in the cans and by rinsing the contents. Obviously, this approach will not work with canned soups, which generally should be avoided. If you like soup, make your own with fresh ingredients and as little salt as possible.
Reducing protein in the diet may also be helpful in postponing kidney failure, as suggested by considerable evidence obtained from animal studies. Because kidneys normally filter protein and return it to the blood, with lower levels of protein, they do not need to work as hard. People with diabetes or glomerular diseases (where protein spills into the urine, reflecting kidney damage) can improve their health by eating less protein. In addition, you might eat soy or other plant protein, like legumes and whole grains, rather than animal protein. Although researchers have not extensively studied protein intake levels in humans, reducing the amount of protein you consume has little downside risk and might be beneficial to your health. People with advanced kidney failure should exercise caution, however. Reducing your protein intake may result in insufficient caloric intake and may put you at significant risk of malnutrition. Talk to your nephrologist and your dietitian to strike the right balance.
As we learned in chapter 2, phosphorus in the form of phosphate is an important element in many energy-producing reactions of the body. Because we consume more phosphorus than we need, the kidney must excrete the excess amount. Limiting phosphorus intake can help take the load off your kidneys. When a person’s kidney function is poor or the person is on dialysis (see chapter 6), it is even more important to limit phosphorus consumption. Cola drinks and dairy products are a main source of phosphorus and may have to be consumed in small amounts only. Rice milk is a suitable substitute for skim milk. Soy milk contains too much phosphorus.
It’s easy to eat the wrong foods, in part because we do not understand what’s in the food we’re eating. Learn to read a food label as one way to help avoid eating harmful foods. Figure 5.1 shows an example of a typical food label—for packaged macaroni and cheese. Several items on the label are particularly pertinent for people with failing kidneys as well as for people trying to lose weight.
First, check the serving size. It can be easy to buy an item that looks as if it is a single serving when it is not. A small package of snacks or bottle of soda represents more than one serving. As figure 5.1 shows, eating the entire item means consuming two servings and double the calories, fat, and salt of the single serving as gauged by the food manufacturer.
If you are limiting fat intake, check the number of calories contributed by fat, which is listed next to the number of total calories per serving. Consider that the label indicates that a single serving contains 110 calories from fat, while there are 250 total calories in the single serving. This means that almost 50 percent of the calories in a single serving comes from fat! And the percentage is often much higher for cheeses and cooking oils, so people who consume a lot of these foods are taking in more fat and calories than they might realize. Check the labels. Look for food where the majority of the calories come from a source other than fat.
Figure 5.1. A Typical Food Label
Fat, cholesterol, and sodium—the substances labeled “Limit These Nutrients” in figure 5.1—should be consumed only in small amounts if you have kidney disease. A high-fat and high-salt diet can lead to the formation of fat deposits in blood vessels and to high blood pressure, heart disease, and some cancers. Some fats, however—those designated as monounsaturated or polyunsaturated, like olive oil—may be beneficial. The nutrients labeled “Get Enough” are healthy and should be consumed in large amounts. Some people do not get enough vitamins and minerals in their diets and may need to take supplements to satisfy their daily requirements.
The footnote at the bottom of a food label provides basic nutritional information, based on the advice of experts, on the upper and lower limits you should consume daily, depending on the number of calories consumed. Values for fat, cholesterol, and sodium represent the upper limit, whereas the dietary value for fiber is the minimum daily amount most people need. Based on those guidelines, the percentage of the daily values provided by the food (in this case, the packaged macaroni and cheese) is listed by each item. A value of 5 percent or less is low, whereas 20 percent or more is high. These values provide comparisons among food items so it’s easier to identify which foods are best for your diet.
Unfortunately, food manufacturers are not required to list the potassium or phosphorus content per serving on their food labels. This poses a unique challenge for people with kidney disease. Some manufacturers list them voluntarily, helping you to know which products are safe to eat and which items are to be avoided. Chapter 6 lists some foods that are high and low in potassium and phosphorus.
Although obesity can contribute to hypertension, not everyone with hypertension is overweight. In obese people and in people with hypertension, however, diet alone may not lower blood pressure to the desirable 120/80 or below. Some people must take medications to control high blood pressure.
Recent research suggests that maintaining a blood pressure of 125/75 can postpone kidney failure for years. Luckily, the treatment of hypertension has evolved over the last four decades, and today there are many classes of medications working through different mechanisms to control blood pressure. Although a single medication may be effective in controlling hypertension, clinical research has shown that a combination of medications may be needed to reduce high blood pressure. Working through different mechanisms, some classes of medications may be better than others in protecting kidney function.
In chapter 2, I discussed a biochemical process initially mediated by the kidney that can cause hypertension. This process involves the release of the hormone renin from the kidney. Renin activates angiotensin synthetic pathways, whereby angiotensin II constricts blood vessels and increases blood pressure.
There are two ways to interfere with the ability of angiotensin II to elevate blood pressure: block the production of angiotensin II or reduce the actions of angiotensin II on blood vessels. Medications that block the formation of angiotensin II are called angiotensin-converting enzyme, or ACE, inhibitors. One such medication is lisinopril (Zestril and Prinivil). These drugs have been in use for many years, have been well studied, and might be especially beneficial in protecting kidney function. Another drug that blocks angiotensin II receptors is losartan (Cozaar). This drug also reduces blood pressure effectively. Because one of these drug classes may not be sufficient to lower blood pressure to the desired level, the effectiveness of combining both classes of drugs is currently under investigation for treating PKD.
The other drug classes that can reduce blood pressure do so directly by relaxing blood vessels or altering heart rate and the amount of blood the heart ejects with each beat (cardiac output)—or through a combination of these effects. At the cellular level, all of these drugs work by blocking receptors that normally translate the signals of the body’s hormones or chemical transmitters into a physiological response. Two classes of drugs that lower blood pressure act on the heart and, to some extent, on the blood vessels directly. One class, named beta-blockers, slows the heart rate and reduces cardiac output, thereby lessening the burden on the heart and reducing blood pressure. Atenolol (Tenormin) is a commonly prescribed beta-blocker. The other class of drugs acting on the heart and blood vessels includes the calcium-channel blockers. These drugs prevent the inflow of calcium into cells that stimulate the contraction of muscle in the heart and blood vessels, thereby lowering blood pressure.
As we learned earlier, hypertension is often difficult to treat with only one class of drug. To control your hypertension, you may need to take several different classes of drugs with different actions, and possibly others as well, including, for example, diuretics (water pills) like hydrochlorothiazide (Microzide); alpha-blockers like terazosin (Hytrin), which acts directly on the blood vessels, or others, which work through the brain; and minoxidil (Loniten), which directly opens blood vessels. Your doctor may determine the best treatment for your hypertension by trial and error.
Preventing kidney failure depends on effectively treating the underlying causes of kidney failure. There are many ways to treat hypertension in a person who has no other underlying diseases. However, there are not as many ways to treat diabetes, glomerular diseases, and PKD. Clinical researchers are always working to develop new, more effective drugs. They do this by first studying relevant mechanisms in animal trials. If the results are promising, they move ahead to clinical trials using human volunteers. The federal government has established a website that lists current clinical trials: www.clinicaltrials.gov. On this website you can find information about current research and applications. There are some promising new approaches to treating the underlying diseases that can lead to kidney failure. Here are a few examples of what clinical researchers are pursuing. (When reading these descriptions, keep in mind that, in scientific and medical research, new treatment possibilities emerge while others become dead ends.)
The first line of treatment for diabetes is controlling glucose and insulin levels. For people with mild diabetes, a healthy diet is the first step. The body’s supply of glucose and insulin is further regulated through medications that are taken orally. People with Type 1 diabetes take insulin either intramuscularly (as an injection into muscle tissue) or subcutaneously (by using an infusion pump under the skin that continuously releases insulin). None of these treatments is a cure for diabetes; clinical trials are under way to find better treatments or a cure for both Type 1 and Type 2 diabetes.
Researchers are working to develop better drugs that can control cellular responsiveness to insulin. People with Type 2 diabetes are insulin resistant and may benefit from oral medications that improve insulin responsiveness. Insulin responsiveness is a prime target for research. Although these types of drugs have been available for decades, they have not been very effective in people with severe diabetes. For these people, insulin injections are needed to control blood glucose levels. Future drugs may be more effective in controlling insulin resistance, meaning that more people with diabetes can eliminate or postpone the need to take insulin. In the long term, these drugs may reduce the number of people with diabetes experiencing kidney failure.
Clinical studies on Type 1 diabetes are looking for better treatment options to protect the insulin-producing beta cells from being destroyed by the body’s own antibodies. The current treatment approach of suppressing the immune system, which interferes with all immune reactions, makes people more vulnerable to infections. The goal of the latest research is to find specific pathways in the immune response that attack beta cells rather than the immune system as a whole. Research is slowly identifying the pathways to the best targets for therapeutic intervention as well as effective new medications.
Another way to treat Type 1 diabetes is to desensitize the specific immune response that damages beta cells, so that the pathway is less responsive to autoimmune attack. Desensitizing the immune response also reduces the chance that a transplanted organ will be rejected by the body. I participated in such a clinical trial when I received my kidney transplant (see chapter 7). In islet transplants, pancreatic islet cells from deceased donors are infused into a patient to restore insulin secretion without the patient needing to use steroids to suppress system-wide immune responses.
New treatments for glomerular diseases are emerging, too. The approach of these treatments varies depending on the original source of the disease (see chapter 3). Glomerular diseases are inflammatory diseases that lead to scarring of the glomerulus, and most of the treatment options reduce this inflammation using steroids. Most clinical trials on inflammation focus on inflammatory diseases like lupus. Here, similar to the studies of Type 1 diabetes, researchers are examining pathways within the immune system to find the most selective approach to minimize or slow the scarring, without using steroids.
One clinical trial is testing a drug that reduces scar formation. Unlike drugs that suppress the immune system, this drug (pirfenidone) acts by blocking the development of scar tissue. The goal is to prevent further scarring in people with declining kidney function.
Clinical trials to find medications to retard cyst growth in PKD patients are pursuing what is perhaps the most promising approach for treating a major cause of kidney failure. Having developed a better understanding of the underlying mechanisms of how cysts form in the kidneys, researchers have been looking for ways to shrink the size of the cysts. In addition to a multi-center trial combining drugs that act on the angiotensin system, as discussed earlier, other studies are taking additional approaches.
The most advanced of these clinical trials involves blocking the action of the hormone vasopressin. Vasopressin, which is released from the pituitary gland to conserve fluid in the body, does so by stimulating cellular mechanisms that can cause cyst formation and growth in people with mutations in their PKD genes (see chapter 3). Indeed, vasopressin levels are higher in PKD patients. An inhibitor of vasopressin can retard cyst formation in a mouse model of PKD. Tolvaptan, an inhibitor of vasopressin, is currently in Phase III clinical trials to determine how effective and safe it is in treating PKD.
Other drugs are being developed to inhibit the size and number of cysts by blocking their blood supply, without which they die. A similar strategy has been successful for treating some types of cancer. One study uses a drug called sirolimus to suppress the immune system in people receiving organ transplants. Researchers found that PKD kidneys and livers shrank after transplant in patients taking sirolimus, unlike what happens when such patients take other immunosuppressants. If this drug works in blocking cyst formation and growth in humans, it could help with the development of new drugs without an immunosuppressant effect.
New research on the underlying causes of kidney failure and the development of potential treatments offer hope to people in fear of losing their kidney function and of facing dialysis or transplantation. Someday, we hope, there will be no need for dialysis clinics and transplant lists and less need for expensive and invasive medical interventions. In the future, the lives of many people with kidney diseases will improve.
In the meantime, people approaching kidney failure must examine the choices available to replace their impending kidney failure. Chapters 6 and 7 cover what you can expect with dialysis and transplantation, and introduce some coping skills that I found helpful.