End-stage renal disease in people with type 2 diabetes: systemic manifestations and exercise implications.

[Evans N, Forsyth E. End-stage renal disease in people with type 2 diabetes: systemic manifestations and exercise implications.]

Key Words: Diabetes, Exercise, Nephropathy, Systemic.

Epidemiology

In 1994, an estimated 12 million Americans had diabetes, and that number increased to 16 million in 1999. (1-4) It is now estimated that 17 million people have diabetes. (5) The United States has demonstrated a 12% increase in prevalence of people with diabetes in the last decade. (6) The prevalence has doubled among African Americans, tripled among Hispanic Americans, and also increased among Native Americans. (7) In addition, approximately 1,800 new cases of diabetes are diagnosed each day, or approximately 655,000 new cases each year. (4) According to Clark and Clark, "we are in the midst of an epidemic of diabetes affecting an estimated 110 million people worldwide." (2(p330)) Furthermore, the number of people with diabetes is expected to double during the next 2 decades as a result of many countries embracing a Western lifestyle that usually includes decreased physical activity and increased obesity. (8,9)

Type 2 diabetes, formerly known as adult-onset or non-insulin-dependent diabetes mellitus, comprises 90% of all cases of diabetes and has a slow and insidious onset. (9-11) According to Ludwig and Ebbeling, (12) however, age may no longer be a factor when distinguishing between type 1 and type 2 diabetes. There is an increase in the number of children currently being diagnosed with type 2 diabetes, which is most likely a result of an increase in obesity among children. In type 2 diabetes, insulin secretion is normal or increased. The target cells in the body, however, are less sensitive to insulin, and, therefore, the cells cannot effectively utilize glucose for energy. Long-term obesity is a risk factor for developing type 2 diabetes, as 80% of individuals with type 2 diabetes are considered to be obese, having a body mass index (BMI) greater than or equal to 30 kg/[m.sup.2], whereas the other 20% are above their ideal weight or have a BMI of 25 to 29.9 kg/[m.sup.2]. (10,13) Type 2 diabetes has a higher incidence rate among African Americans, Native Americans, Japanese, Puerto Ricans, and Hispanics. (10,11) Type 2 diabetes can be controlled by diet alone or by a combination of medications (oral hypoglycemics or insulin), exercise, and diet.

Overview of Macrovascular and Microvascular Complications

Regardless of practice setting, physical therapists will frequently encounter and treat patients with diabetes as a result of its high prevalence. Individuals with diabetes are at risk of developing macrovascular and microvascular complications, resulting in widespread effects on numerous systems of the body. (2,7,9,14) Macrovascular complications consist of coronary heart disease, peripheral vascular disease, and cerebrovascular accident. Common microvascular complications of diabetes include neuropathy, retinopathy, and nephropathy. Nephropathy that progresses to end-stage renal disease (ESRD) is perhaps the most complex microvascular complication due to its detrimental effects on numerous systems of the body. As a result, many physical therapists may find it challenging to treat people with ESRD. This article will describe: (1) the systemic manifestations of ESRD, (2) exercise guidelines for people with type 2 diabetes, and (3) exercise guidelines for people with ESRD. The purpose of this article is to guide physical therapists in providing appropriate exercise interventions for people with type 2 diabetes and ESRD.

Stages of Nephropathy

Diabetic nephropathy is the primary cause of ESRD. (15-18) In 1991, it was estimated that diabetes accounted for 40% of the newly diagnosed cases of ESRD. (11) Between 10% and 20% of people with diabetes will develop ESRD. (11,19-22) Nephropathy occurs more frequently in people with type 1 diabetes than in people with type 2 diabetes. However, the majority of cases of nephropathy occur among people with type 2 diabetes because of the vastly higher incidence of type 2 diabetes. (23,24) Individuals with diabetes and ESRD have higher morbidity and mortality rates than individuals with ESRD only. (25)

According to the National Institute of Diabetes & Digestive & Kidney Diseases, there are 5 stages that describe the progression of diabetic nephropathy. (26) During stage I, hyperfiltration occurs and the glomerular filtration rate (GFR) increases as healthy individual nephrons attempt to compensate for the damaged nephrons. Unfortunately, there are no symptoms during the early stages of diabetic nephropathy; however, with early detection and proper glycemic control, stage I is reversible. (10,23,26) Some individuals will remain in stage I indefinitely, whereas others will progress to stage II. (26)

During stage II, the damaged capillaries allow small amounts of albumin to be excreted in the urine. Between 13% and 41% of people have microalbuminuria when first diagnosed with type 2 diabetes. (27,28) Individuals may remain in this stage for several years by achieving proper control of hypertension and blood glucose levels. (26)

Stage III is when diabetic nephropathy is first noticeable. As albumin levels increase in the urine, levels in the blood are lowered, resulting in noticeable edema. (15,26) In addition, levels of creatinine and blood urea nitrogen (BUN) increase. (26) The accumulation of these waste products in the blood is called azotemia. Early detection at this stage is vital to preserve kidney function and to delay or prevent ESRD. (18) According to the National Institute of Diabetes & Digestive & Kidney Diseases, individuals with type 2 diabetes may remain in this stage for several years. (26)

Stage IV is often referred to as advanced clinical nephropathy, and kidney damage is irreversible. (26) Proteinuria is the hallmark of this stage. (29,30) The kidneys are no longer capable of excreting toxins and accordingly there is a progressive increase in BUN and creatinine levels. (23,33) Most people in this stage are hypertensive secondary to increased production of renin. Because hypertension accelerates the progression to ESRD, early detection is vital. (18) If not treated at this stage, uremia and death will follow within 7 to 10 years. (23,31)

Stage V, or ESRD, is when the kidneys fail to function, the GFR severely decreases, and hypertension continues to worsen. (32) During this final stage, the kidneys cannot excrete toxins; maintain fluid, pH, and electrolyte balances; or secrete important hormones (renin, vitamin D, and erythropoietin). As a result, a multitude of symptoms become apparent that involve most major organ systems in the body. (30)

Systemic Manifestations of ESRD

Musculoskeletal System

When the kidneys are functioning properly, parathyroid hormone (PTH) lowers phosphate levels by reducing renal tubular phosphate reabsorption and raising phosphate excretion. When the GFR decreases to 20% to 30% of normal, hyperphosphatemia occurs and triggers secondary hyperparathyroidism. (33-35) However, increased levels of PTH liberate calcium and phosphorus from the bones into the extracellular fluid, only compounding the hyperphosphatemia. In addition, bones become resistant to the action of PTH. (30)

Renal osteodystrophy is the result of pathological changes in the bones, and at least 80% of people with this condition show increased osteoclastic activity, when beginning dialysis treatment. (30) Individuals may complain of pain in the spine, hips, knees, or lower extremities. The pain worsens with exercise and other weight-bearing activities, and fractures are common in the vertebrae and long bones. Increased secretion of PTH and a decreased secretion of calcitrol appear to be the cause. (36) However, metabolic acidosis also may play a role either by increasing osteoclastic activity or by increasing the effects of PTH. (30)

Myopathy affects the proximal upper and lower extremities and progresses over time, leading to functional disabilities. (36) The gluteus medius, hamstring, and psoas muscles frequently are affected first and most severely. Individuals may experience difficulty ambulating up and down stairs or curbs, rising from low seats, or getting in and out of the bathtub. Later, activities of daily living that involve the upper extremities (eg, brushing teeth, combing hair) may be challenging. (37) Although the etiology of myopathy is not clear, increased levels of PTH, decreased levels of phosphate and vitamin D, and excessive accumulation of aluminum appear to be involved. (30,36)

Spontaneous ruptures of tendons may occur with minimal stress and are commonly observed in the quadriceps, triceps, or extensor tendons of the fingers. (36) The quadriceps tendon may rupture simply by walking, tripping, or ambulating down stairs. These ruptures can lead to pain, deformity, and disability. Hyperparathyroidism and metabolic acidosis are responsible for the abnormal collagen that results in weak tendons. (30,36,37)

Metastatic calcification commonly occurs during ESRD. Vascular calcification of arteries, resulting in vascular insufficiency, may be observed via radiographs in nearly 100% of individuals with ESRD by age 50 years. (38) Visceral calcification arises when calcium phosphate deposits are found in the lungs, skeletal muscle, and myocardium. Calcification deposits also may be found in the conjunctiva of the eye (conjunctival calcification), around the joints (periarticular calcification), and in the synovial fluid of joints (arthritis) secondary to hyperphosphatemia.

Nervous System

Both the central and peripheral nervous systems are affected by ESRD. Early symptoms that affect the central nervous system include decreased ability to concentrate or think abstractly. Later symptoms include apathy, lethargy, lability, and insomnia. Severe symptoms include increased deep tendon reflexes, decreased coordination, clonus, and stupor. (29,30) Coma and death may follow when the BUN level rises to 150 to 200 mg/dL. Psychological features that may follow during the course of ESRD include delusions, depression, mania, and euphoria. The cause of the central nervous system symptoms are not clear but may be due to a toxic increase in PTH or a decrease in brain metabolism secondary to impaired neurotransmission and inhibition of various enzymes. (30)

Neuropathy is another complication for people with ESRD and also is common in people with diabetes. Sixty-five percent of people with ESRD have peripheral neuropathy when beginning dialysis treatment. (30) Individuals may experience sensory loss that is usually distal and symmetrical in the lower extremities and motor loss leading to muscle atrophy. Restless leg syndrome and carpal tunnel syndrome may develop as a result of neuronal damage. (29,30) The pathology of peripheral neuropathy also is unclear, but the neural axons become damaged and demyelinated. Increased levels of PTH may contribute to peripheral neuropathy by raising intracellular calcium levels of the peripheral nerves. (30)

Autonomic neuropathy does not always have consistent clinical manifestations. (39) However, decreased cardiovascular reflexes during hemodialysis occur frequently. (39) Other symptoms associated with autonomic neuropathy include orthostatic hypotension and decreased thermoregulation. (10,39) Another serious complication of autonomic neuropathy is the occurrence of silent myocardial infarctions. (40)

Respiratory System

People with ESRD are susceptible to the development of tuberculosis and other respiratory infections because their immune system is already depressed. Primary pulmonary edema is a common respiratory complication and occurs when the microcirculation becomes leaky. As mentioned previously, visceral calcification may occur as calcium is deposited into the alveolar septae in the lungs, leading to fibrosis. Finally, metabolic acidosis, which occurs in ESRD, results in an increase in ventilation known as Kussmaul respirations (deep rapid breathing with sighing). (41)

Hematologic System

Immunosuppression is common with ESRD; therefore, individuals are highly susceptible to infections, ultimately leading to increases in morbidity and mortality. (42) Anemia often is present in individuals with ESRD, and symptoms include weakness, decreased muscle force, fatigue, shortness of breath, and cardiomyopathy. (30) Thrombocytopenia occurs in 20% of people with ESRD. Symptoms include purpuric lesions, nosebleeds, gastrointestinal bleeding, and bleeding with invasive procedures. (30) Another less common disorder of the coagulation system is calciphylaxis. Characteristics include burning pain, followed by discoloration of the affected trunk, extremities, or digits, secondary to widespread calcification in the stroma and arteries. (43) Skin grafts or amputations often are required, especially if frank necrosis ensues.

Cardiovascular System

Fluctuations in potassium are common during ESRD and can lead to life-threatening complications, such as fatal arrythmias. Hyperkalemia may be due to increasing potassium intake or acidosis. Factors contributing to hypokalemia include a decreased dietary intake or hyperaldosteronism. Diuretics can cause potassium levels to increase or decrease depending on the type used. (29)

Hypertension, which is common among individuals with type 2 diabetes, increases the risk of cardiovascular morbidity and accelerates the progression of kidney disease. (30,44-46) However, kidney diseases also can lead to secondary hypertension as a result of changes in the renin-angiotensin system. The incidence of hypertension increases with the degree of renal insufficiency, and most people have hypertension during ESRD. (30)

Congestive heart failure frequently occurs. The pathology is multifactorial; however, anemia, atherosclerosis, fluid overload, elevated PTH levels, and hypertension are believed to be contributing factors. (30) Symptoms of congestive heart failure include shortness of breath, dyspnea on exertion, palpitations, chest pain, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, ascites, pulmonary edema, and pulmonary effusion. (29,30)

Pericarditis is another cardiovascular complication of ESRD and is characterized by jugular venous distension, Kussmaul sign (pulse increases during exhalation and decreases during inhalation), and a decrease in systolic blood pressure and in pulse pressure. (29) A pericardial friction rub (rubbing together of pericardial layers that is audible with a stethoscope), however, may not be present. Pericarditis is not as common as congestive heart failure, but symptoms include persistent chest pain, fever, (47) and unexplained hypotension. (30) Pericarditis may be life threatening due to the risk of cardiac tamponade. (30)

Raynaud phenomenon can occur secondary to decreased blood flow to the digits. Symptoms include pain, numbness, and tingling with or without exposure to cold temperatures. The ischemia is due to increased levels of PTH and metastatic calcifications in blood vessels. (30)

Cutaneous Manifestations

The skin, which is the largest organ in the body, is affected during ESRD. Uremic frost is white urea crystals that are excreted by the sweat glands and are commonly found on the face and upper trunk. (30,48) People with ESRD have decreased healing of wounds and fractures because collagen synthesis is impaired as a result of acidosis, malnutrition, and hypometabolism. (49) Individuals frequently have pallor secondary to anemia, which is accompanied by a yellow-brown pigmentation due to retained urochrome and carotene. (50) In addition, diffuse hyperpigmentation may be visible in areas exposed to the sun. (51) Xerosis is dry, scaly skin and is common during ESRD. Pruritus, or itchy skin, is a common and often unrelenting symptom that occurs during ESRD and frequently continues after dialysis. Pruritus is believed to result from the formation of a calcium phosphate precipitate in subcutaneous tissues, creating an inflammatory response in the skin. (30) Finally, individuals in ESRD tend to have petechiae or ecchymoses as a result of increased capillary fragility and subcutaneous bleeding. The lower extremities are most commonly affected, and severity correlates linearly with the level of azotemia. (48)

Urogenital System

Changes in urination patterns occur frequently among individuals with ESRD. Prior to ESRD, when the GFR is less than 40 mL/min, polyuria and nocturia occur. However, urine output is decreased (anuria) when the GFR decreases to 5 mL/min. (30) In addition, sexual problems such as decreased libido, impotence, and infertility may occur in both men and women. The cause may be a result of fatigue (secondary to anemia), depression (secondary to illness), and changes in secretion of reproductive hormones. (30)

Gastrointestinal System

Disturbances in the gastrointestinal (GI) tract are seen in individuals with ESRD. Both anorexia and nausea and vomiting are thought to develop secondary to the kidney's inability to excrete toxins. Metabolic acidosis is believed to contribute to decreased appetite and weight loss as well. Furthermore, parotitis (inflammation of the salivary glands) and stomatitis usually occur together. Stomatitis is characterized by painful mouth ulcers, a coated tongue, and a metallic taste in the mouth. (29) Azotemia may lead to the development of diarrhea that is often accompanied with blood secondary to hemorrhagic ulcers in the GI tract. (52) High levels of ammonia are thought to be responsible for both the GI tract and mouth ulcers. (29,52) Disturbances in metabolism may result secondary to anorexia, nausea and vomiting, and poor nutrition, which can lead to a negative nitrogen balance and poor protein intake. (29)

General Exercise Guidelines for People With Type 2 Diabetes

According to Funnell and Anderson, (53) people with diabetes often do not receive adequate care, education, and support to successfully manage the disease. Therefore, physical therapists have the opportunity to educate people with type 2 diabetes regarding the physiology of exercise as well as the potential benefits and complications. Physical therapists play a vital role in ensuring that people with type 2 diabetes exercise both safely and effectively. (54) Exercise, along with diet and medication, is a crucial component to manage type 2 diabetes and prevent serious complications. There is no present research indicating that individuals with type 2 diabetes who follow prescribed exercise programs with appropriate precautions are at increased risk for adverse effects of exercise compared with individuals without diabetes. (54) Exercise is necessary to achieve cardiovascular fitness, appropriate body composition, and muscular strength and endurance. (55) Other potential benefits include increased insulin sensitivity and decreased serum glucose levels. (56-58) In addition, exercise decreases the risk of heart disease by reducing body weight, lowering blood pressure and low-density lipoproteins, and raising high-density lipoproteins. (56-58) Psychological benefits achieved through exercise include improved fitness and self-esteem and decreased anxiety. (54,57)

Aerobic Exercise Guidelines

A cardiopulmonary exercise program should be performed between 3 and 5 days per week. (55) The exercise should be performed at a low to moderate level of intensity (40%-70% of maximum oxygen consumption) to maximize health-related benefits, minimize risks, and increase adherence to the exercise program. (55,56) Because people with type 2 diabetes often have autonomic neuropathy, the ratings of perceived exertion (RPE) scale should be used in addition to or instead of monitoring the heart rate. (59) The duration of the cardiopulmonary exercise should be 10 to 15 minutes initially and should gradually be increased to 30 minutes. (60) However, recent guidelines published by the Institute of Medicine suggest that all individuals who want to stay healthy should perform moderate exercise for 60 minutes each day. (61) Weight loss is best achieved by exercising for an extended duration (ie, 60 minutes) while maintaining a low to moderate level of intensity. (62)

In order for the individual with type 2 diabetes to become motivated and make a lifestyle modification, it is imperative that the mode of aerobic exercise is enjoyable and coincides with individual goals. (56,57) Walking is one of the most common physical activities performed by people with type 2 diabetes. (63) People with type 2 diabetes often must perform exercises that are non-weight bearing or must alternate between weight-bearing and non-weight-bearing activities if complications such as peripheral neuropathy or peripheral vascular disease are present. (60,64) The exercise program may be progressed after an individual with type 2 diabetes can tolerate 10 to 15 minutes of aerobic exercise at a low intensity for 3 to 5 days per week. The duration of the aerobic exercise should be gradually increased first, while maintaining a low to moderate level of intensity. (55) Intensity level is the last to be progressed and should be increased in small increments and monitored closely to avoid fatigue or injuries. (55)

Resistive Exercise Guidelines

A resistive training program should be performed 2 or more times per week, with the intensity (amount of weight) being low to moderate. At least 8 to 10 exercises should be performed that target the major muscle groups of the body. A minimum of one set consisting of 10 to 15 repetitions should be performed. (55) According to the American Diabetes Association, a safe and easy method to initiate a resistive training program is to start with the weight that can be lifted for 6 to 10 repetitions before fatigue for each exercise. The individual is then monitored to ensure that heart rate and blood pressure remain within limits that were previously determined for the individual via a graded exercise test and that the RPE scale score is less than 13 (somewhat hard). (65) Once the individual can tolerate this weight, the repetitions can be increased to 10 to 15 and then to 15 to 20 every 1 to 2 weeks. (65) After individuals can perform 2 to 3 sets of 15 to 20 repetitions, weight may be increased by 0.91 to 2.27 kg (2-5 lb) for the upper extremities and by 2.27 to 4.54 kg (5-10 lb) for the lower extremities. (65) Another method to determine the amount of weight is the 1 repetition maximum (1 RM). Resistive loads are classified as light (40%-60% of 1 RM), moderate (60%-80% of 1 RM), and heavy (80%-100% of 1 RM). (65) However, according to Hornsby, (65) the former method may be more easily implemented in the clinic and may provide a more accurate exercise prescription for the individual.

Precautions

There are precautions that must be considered when prescribing an exercise program for people with type 2 diabetes. Prior to initiating an exercise program, people with type 2 diabetes should first be examined by a physician to screen for the presence of macrovascular or microvascular complications. In addition, individuals aged 35 years or older should undergo a stress test to determine cardiopulmonary fitness and to screen for autonomic neuropathy. (59,60) The systolic blood pressure should remain below 180 mm Hg, and the diastolic blood pressure should remain below 105 mm Hg during exercise. (59) Individuals must be educated regarding the importance of proper footwear and daily foot inspections, especially if neuropathy is already present. (54,57)

People with type 2 diabetes must avoid exercising in extremely hot or cold temperatures or when glucose levels are poorly controlled. Exercise is contraindicated if glucose levels are greater than 300 mg/dL (greater than 240 mg/dL in people with ketosis). (59) Although it is uncommon for individuals with type 2 diabetes to experience exercise-induced hypoglycemic episodes, unless taking oral sulfonylurea medications or insulin, glucose levels should be monitored before and after exercising. To avoid hypoglycemia during exercise, carbohydrate intake should be increased by 15 g*[h.sup.-1] when exercise is longer than 60 minutes in duration. (66,67) Individuals who are trying to lose weight should consult with their physician to reduce insulin dosage before increasing carbohydrate intake. (55) Drinking water before, during, and after exercise is vital for maintenance of adequate hydration. (54,55) Lastly, it is recommended that individuals wear a visible label while exercising that will identify them as having type 2 diabetes. (68)

To ensure safety, individuals with diabetic complications may require supervision and may need to make appropriate modifications to a resistive training program. This is particularly true for individuals with cardiac or retinal complications. (55) Decreasing the intensity of training, avoiding exhaustion, and eliminating sustained gripping or isometric contractions can prevent increases in blood pressure secondary to exercise. Ways to accomplish this include instruction in proper lifting and breathing techniques to avoid the Valsalva maneuver.

Additional Exercise Guidelines for Individuals With ESRD

The exercise guidelines for people with type 2 diabetes are similar to those for people in good health. Individuals with ESRD need additional considerations when implementing an exercise program, secondary to the systemic consequences of nephropathy. Individuals with ESRD have a low activity tolerance with an average maximal oxygen consumption of 20 mL*[kg.sup.-1]*[min.sup.-1] or half of the value expected for individuals in good health of the same age. (69) According to Painter, (69) individuals with ESRD may have decreased exercise capacity, due to: (1) decreased cardiac output and a blunted heart rate response, (2) anemia, and (3) decreased ability to extract oxygen secondary to musculature changes.

Exercise Testing

The efficacy of exercise testing prior to initiating an exercise program for people with ESRD is questionable. The primary limiting factor during the exercise test appears to be muscle fatigue, and individuals are therefore unable to reach the desired maximum intensity level. As a result, the exercise test may cause unnecessary fatigue and provide no new diagnostic information. (69)

Exercise Prescription

The most appropriate exercise prescription for people with ESRD is yet to be determined. (69) However, there are some general guidelines to be considered. The recommended exercise freqnency for individuals with ESRD is between 4 and 6 days per week. (70) Because these individuals have low exercise capacity, interval training may be the best method when initiating a program. Lower extremity fatigue impedes continuous exercise and is the most common reason for termination of exercise. The goal should be to exercise continuously for 30 minutes. (70) The intensity should be low, especially on days that dialysis is administered. (70) The RPE scale should be used to monitor intensity for the same reasons as discussed previously.

The mode of exercise must be considered, especially in the presence of orthopedic complications. Individuals may need to implement non-weight-bearing activities and, in cases of severe deconditioning, may need to initiate resistive training prior to aerobic activities. (70) Progress with the individual's exercise program may be impeded by frequent hospitalizations, necessitating the exercise program to be reinitiated; therefore, encouragement from the health care team is essential. (70) Although probably unrealistic, it has been recommended that people exercise in a controlled environment where they can be closely monitored secondary to systemic and cardiac complications. One study by Painter et al (71) showed positive results when individuals ride a stationary bike and exercise during their dialysis treatment.

Benefits of Exercise Training

Desired and documented benefits of exercise for people with ESRD include improved lipid profile, (70) increased glucose metabolism, (70) increased hematocrit and hemoglobin levels, (72,73) and improved psychosocial effects. (74) However, not all individuals will receive these benefits from an exercise program due to the systemic consequences of ESRD. (69) Individuals on dialysis may receive few, if any, benefits, but when the baseline functional exercise capacity is very low, even small improvements can have an impact on quality of life. (69)

Moore et al (75) implemented an exercise training program using a cycle ergometer during hemodialysis treatment for 12 weeks. Participants were 11 patients who received hemodialysis 3 to 4 hours, 3 days a week. Adherence to the program was encouraged, and 5 to 10 minutes was added per session until the participants could exercise for 30 minutes. The duration of exercise then was gradually increased to 60 minutes. The workload also was increased to 70% of peak heart rate or greater (6/10 on the RPE scale). Six participants increased their peak oxygen consumption, although there were no changes in heart rate, stroke volume, or arterial-venous oxygen difference. All participants, however, benefited from the training program, as demonstrated by a decrease in heart rate at submaximal workloads and an increased exercise capacity. (75)

Painter et al (76) studied the effect of exercise and erythropoietin in 48 participants who received hemodialysis. Participants were divided into 4 groups: (1) a group that did not receive either erythropoietin or exercise training, (2) a group that received exercise training but that did not receive erythropoietin, (3) a group that received both erythropoietin and exercise training, and (4) a group that received erythropoietin without exercise training. Participants in groups 3 and 4 received erythropoietin 3 times per week. Participants in groups 2 and 3 exercised 3 times per week for 10 to 15 ntinutes on a stationary cycle during dialysis without resistance and added 2 to 3 minutes per session until 30 minutes of continuous exercise was achieved. Intensity was monitored using the RPE scale. Exercise training increased the oxygen consumption in participants in groups 2 and 3, but there was no change in oxygen consumption in participants in group 4. Participants reported improved physical functioning via the Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire (SF-36). These studies (75,76) indicated that individuals with ESRD have a limited exercise capacity due to several factors (ie, anemia, autonomic dysfunction, muscle dysfunction, and long-term physical inactivity), but that exercise can have a positive impact on quality of life.

As a result of the systemic complications of ESRD, individuals may have frequent setbacks and become frustrated with the exercise program. However, exercise offers these individuals the opportunity to be active participants in their treatment and is a proven method to increase functional activity tolerance and therefore should be encouraged. According to Painter, (70) individuals with nephropathy often do not receive education or encouragement to participate in an exercise program. Physical therapists, therefore, have the opportunity to educate both patients and health care professionals regarding the improved quality of life and other benefits that can be achieved through exercise.

Implications of Laboratory Values

Physical therapists must be aware of patients' laboratory values prior to initiating intervention. This is especially important when managing individuals with ESRD who are undergoing dialysis. It is also essential for physical therapists to be aware of the clinical manifestations of various abnormal laboratory values. People with ESRD often have anemia and, therefore, have low levels of hemoglobin. These individuals have a poor exercise tolerance and increased fatigue, and they may have tachycardia. (77) Individuals with a low hematocrit may have shortness of breath, increased fatigue, or chest pain with exertion. (78) The Table gives specific exercise considerations related to hemoglobin levels.

Glucose levels may fluctuate excessively with this patient population. Common clinical manifestations of hypoglycemia include dizziness, headaches, shakiness, hunger, and sweating. Patients who are hyperglycemic may have weakness, nausea and vomiting, and abdominal pain. Diabetic ketoacidosis is a serious condition that may lead to a coma and death. Important signs and symptoms to be aware of include Kussmaul respirations, acetone breath, dehydration, and a weak, but rapid, pulse. (10,77)

People with ESRD may tolerate potassium levels up to 5.5 mEq/L; however, abnormally elevated levels may lead to electrocardiogram changes such as peaked T waves, widened QRS complexes, and depressed ST segments. (79) Symptoms of hyperkalemia include irritability, nausea and vomiting, and diarrhea. Hypokalemia is manifested by arrhythmias and decreased contractility of all muscles types, leading to weakness, paralysis, and hyporeflexia. (79) Calcium is vital for bone structure and muscle movements. Hypocalcemia may cause muscle twitching and cramping, seizures, hair loss, depression, cataracts, or conjunctivitis. (78) Individuals with hypercalcemia may have muscle weakness, fatigue, abdominal cramps, poor appetite, nausea and vomiting, and constipation. Hypercalcemia may lead to a coma if not treated. (78)

Creatinine is a protein that is the by-product of muscle metabolism. Unfortunately, there are no signs and symptoms of abnormal levels. Urea is a waste produce of protein metabolism and is high in individuals with ESRD. Signs and symptoms may include fatigue, nausea, insomnia, dry or itchy skin, and urine odor to body or breath. The Table provides laboratory values that should be considered by a physical therapist when managing an individual with ESRD.

Conclusion

Type 2 diabetes increased in prevalence by 7.4% in 1995 and is expected to increase to 9% by 2025. (80) In addition to the 17 million Americans who are diagnosed with diabetes, another 16 million Americans have pre-diabetes or are at risk for developing the disease. (5) Individuals with diabetic nephropathy are often complex patients to manage as a result of the multitude of systemic complications. Physical therapists can increase the functional capacity and improve quality of life for individuals with type 2 diabetes and ESRD by developing an appropriate exercise program. More research is needed to provide specific recommendations for this patient population.

Table.
Laboratory Values for People in Good Health and
for People With End-Stage Renal Disease (ESRD)
Undergoing Dialysis (77, 78, a)

                         People in Good
Lab Test                 Health            People With ESRD

Hemoglobin (g/dL)        M: 14-18          11.5-12.5
                         F: 12-16

Hematocrit               M: 42%-52%        M and F: 33%-36%
                         F: 37%-47%

Glucose (mg/dL)          80-120            80-120

Potassium (mEq/L)        3.5-5.0           4.0-6.0

Calcium (mg/dL)          8.5-10.5          8.5-10.5

Creatinine (mg/dL)       M: 0.6-1.2        10-20
                         F: 0.5-1.1

BUN (mg/dL)              10-20             40-85

WBC (cells/[mm.sup.3])   5,000-10,000

Platelets                150,000-400,000
  (cells/[mm.sup.3])

Lab Test                 Special Considerations

Hemoglobin (g/dl)        <8: no exercise permitted
                         8-10: light exercise permitted
                         >10: resistive exercise permitted

Hematocrit               <25%: no exercise permitted
                         >25%: light exercise permitted
                         30%-32%: add resistive exercise as tolerated

Glucose (mg/dL)          >300 or >240 with ketosis

Potassium (mEq/L)        Critical values: <2.5 or >6.5
                         No active exercise: <3.2 or >5.1

Calcium (mg/dL)          Critical values: <6 (tetany) or
                           >14 (coma)

Creatinine (mg/dL)

BUN (mg/dL)

WBC (cells/[mm.sup.3])   <5,000 with fever: no exercise
                         >5,000: light exercise and may progress to
                           resistive exercise as tolerated
                         High range normal may indicate infection in
                           people with ESRD

Platelets                <20,000: no exercise permitted
  (cells/[mm.sup.3])

(a) M=male, F=female, BUN=blood urea nitrogen, WBC=white blood cells.

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N Evans, PT, MSPT, CTRS, was a graduate student, Krannert School of Physical Therapy, University of Indianapolis, at the time of this research, which was undertaken in partial fulfillment of the requirements for her Master of Science in Physical Therapy degree.

E Forsyth, PT, PhD, is Adjunct Professor, Krannert School of Physical Therapy, University of Indianapolis, 1400 E Hanna Ave, Indianapolis, IN 46227 (USA) ([e-mail]). Address all correspondence to Dr Forsyth.

Dr Forsyth provided concept/idea/project design and institutional liaisons. Ms Evans provided writing. Both authors provided project management and consultation (including review of manuscript before submission).