The following are the features of a gradually developing uremic syndrome: fatigue, slowed thinking, and pruritus that occurs early. As all organ systems become involved, a wide complex of symptoms and findings evolves.
Cardiovascular system
What cardiovascular abnormalities occur with uremia?
Patients with chronic kidney disease (CKD) are the highest risk group of individuals for cardiovascular disease, and cardiovascular events are the major cause of death among dialysis patients. Death from cardiovascular disease is 10 to 30 times higher in dialysis patients than in the general population. The cardiovascular mortality risk is increased twofold to fourfold in patients with diabetes (National Diabetes Information Clearinghouse, 2007).
Hypertension is the most common cardiovascular complication seen in patients with CKD and affects the majority of patients (Table 5-1). Hypertension causes CKD and CKD causes hypertension. Strict blood pressure control can delay the progession of CKD. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends a target blood pressure of less than 130/80 mm Hg in patients with CKD (Snively & Gutierres, 2004). Hypertension is associated with the progression of left ventricular hypertrophy (LVH), which places the patient at an increased risk for cardiovascular morbidity. Expanded extracellular fluid volume from fluid overload associated with sodium retention is the most prevalent cause. Many patients have increased plasma renin activity. Nephrectomy is an option to assist in the control of resistant hypertension, but is rarely seen today with the current pharmacologic agents available for treatment.
Table 5-1 Classification of Blood Pressure for Adults 18 Years and Older
Fluid volume and sodium regulation by diet, antihypertensive medications, and ultrafiltration help in the management of hypertension. Patients are also encouraged to exercise with their physician’s approval, and stop smoking programs or literature should be offered.
Atherosclerosis is a major factor in morbidity and mortality. A defect in liver lipoprotein lipase is a likely cause of increased serum triglycerides. Coronary artery disease, stroke, and peripheral arterial disease are increased.
Myocardial dysfunction presents as LVH resulting from hypertension, anemia, and atherosclerosis. With LVH the left ventricle grows abnormally thick, causing an interference with the normal pumping action of the heart. Signs and symptoms of LVH depend on the cause, but can include shortness of breath, chest pain, arrhythmias, dizziness, and congestive heart failure. The symptoms of LVH can be controlled or improved with the correction of hypertension, anemia, and fluid volume control. Some patients experience no symptoms at all, but progression to cardiac failure is not unusual.
Coronary artery calcification may occur as a result of imbalances in calcium phosphorus metabolism. Calcification of blood vessels, including the coronary arteries, which bring blood to the heart muscle, can place the patient at risk for heart attack and stroke.
Congestive heart failure (CHF) may be acute but is usually a chronic manifestation related to the retention of sodium and water. Symptoms of CHF include edema of the lower extremities, shortness of breath, and often fatigue, weakness, and the inability to perform physical activities. Weight gain from the excess fluid is another common symptom.
Pericarditis is a cardiovascular complication seen in the patient with CKD. The heart is surrounded by a double-membrane sac containing approximately 15 to 20 mL of fluid. This fluid provides lubrication, allowing the layers of the pericardium to glide smoothly over one another during the contraction of the heart. Uremic toxins, fluid overload, or bacterial/viral infections can all irritate the pericardial membrane, causing inflammation of the lining around the heart (the pericardium), which may trigger chest pain and fluid accumulation around the heart (pericardial effusion).
Patients often present with the classic triad of symptoms: chest pain, low-grade fever, and pericardial friction rub. The chest pain is intensified by deep inspiration, swallowing, and coughing and improves when sitting and leaning forward. The pericardial friction rub is harsh and leathery and heard best at the lower left sternal border during systole as the inflamed layers of the pericardial sac rub together. Aggressive dialysis therapy (daily dialysis) with ultrafiltration to minimize uremic toxins and excess fluids is necessary. Heparin therapy during the dialysis treatment is either decreased or not administered to the patient to minimize bleeding into the pericardial space. Antiinflammatory agents, both steroidal and nonsteroidal, may be prescribed to reduce inflammation.
Pericardial effusion can develop when increased fluid invades the pericardial space. Chest pain and elevated temperature will continue but the pericardial friction rub may be absent on auscultation. Hypotension and shortness of breath may also be seen. The fluid is usually bloody; if volume is large, tamponade may result.
Pericardial tamponade occurs when a large volume of fluid fills the pericardial space, compressing the cardiac muscle. Pericardial tamponade may have a slow or immediate onset and is associated with a high degree of mortality.
Integumentary system
What integumentary changes are seen with chronic kidney disease?
Patients with CKD stage 5 present with very brittle hair, nails, and skin due to a decrease in the size and activity of the sweat and sebaceous glands. Calcium may deposit in the skin, causing intractable pruritus leading to excoriations of the skin from the itching. Uremic frost is rarely seen today and only in the patient with advanced uremia that is left untreated. Whitish precipitates of urea crystals deposit on the skin, giving it a “frosty” appearance. The skin color may appear tan-yellow from the pallor of anemia coupled with the retention of urinary pigments called urochromes. Ecchymosis is commonly seen due to platelet dysfunctions.
Immune system
Why are infections a problem?
Leukocyte abnormalities include reduced white blood cell (WBC) count in some patients. Granulocytes have reduced response to infection and low bactericidal activity. In fact, infection is the second most common cause of death in CKD stage 5 patients. Susceptibility is enhanced by malnutrition, age, diabetes mellitus, immune system defects, and the frequency of cannulation and other invasive procedures. The use of central venous catheters is a major source of infection in the dialysis patient and efforts should be made to have them removed as soon as possible and replaced with an internal vascular access, such as a fistula. Caution must be taken when assessing body temperature because hypothermia is common and responses to infection may not be accompanied by fever. Elevated uremic levels impair phagocytosis and suppress the inflammatory response as well as hypersensitivity reactions.
Urea has an antipyretic effect and patients present with subnormal body temperatures. Poor nutrition plays a role in the diminished activity of WBC production.
Good nutrition, handwashing, and hygiene should be encouraged to help minimize infectious processes. It is recommended that all dialysis patients receive the pneumococcal, influenza, and hepatitis B vaccines.
Gastrointestinal system
What are some gastrointestinal manifestations of uremia?
Uremic individuals have a poor appetite and are often nauseated. The nausea will often diminish after dialysis is initiated and the circulating uremic toxins are reduced. Altered taste and dry mouth are common. Patients often complain of a metallic taste in the mouth, which leads to decreased appetite. The circulating uremic toxins cause nausea and vomiting, which can also be aggravated by intradialytic hypotension. Gastrointestinal bleeding, often occult, is aggravated by medications (aspirin, heparin) and by the platelet defects. Uremic fetor is characteristic of the patient with kidney disease and is the smell of urine or ammonia on the breath from decomposing urea. Gastrointestinal bleeding is seen from irritation of the gastrointestinal mucosa from the uremic environment and from capillary fragility as urea in the gastrointestinal tract breaks down, releasing the irritant ammonia. Diarrhea may be seen from intestinal irritation or hyperkalemia.
Functional constipation is frequent in patients on dialysis due to medications, fluid restrictions, low-potassium and low-fiber diet, and decreased activity levels. Discretion must be used in the choice of laxatives because many products used to manage constipation contain magnesium, phosphorus, or potassium.
Why is prevention of constipation important?
Because of a restricted diet, limited fluid intake, and regular ingestion of phosphate binders, CKD patients tend to become constipated or develop fecal impactions. As older patients are taken into dialysis programs, there is more functional constipation. Such patients have a high incidence of diverticula of the colon. In addition, diverticulitis or perforation is not rare. Hematomas of the bowel and perforation caused by injudicious enemas have occurred. Cathartics and laxatives should be avoided. Stool softeners seem to work well, although they are often required in larger than usual doses. Patients should be encouraged to eat a high-fiber diet, to adhere to a program of regular exercise, and to plan a regularly scheduled time for bowel movements to reduce the problems of constipation. Severe constipation may also cause hyperkalemia because stool potassium losses account for up to 40% of total body potassium losses per day in dialysis patients (see Chapter 14).
Is peptic ulcer disease common in dialysis patients?
Some reports cite an increased incidence of peptic ulcer disease in dialysis patients; others do not. There are reports of higher than normal gastric acidity related to high blood levels of gastrin, which may relate to parathyroid overactivity. Other studies indicate low gastric acidity related to increased urea and ammonia content of gastric juice. Literature suggests that the incidence of ulcer disease is about the same as for the nonuremic general population.
Does ascites occur in chronic kidney disease patients?
Ascites (a massive fluid collection in the peritoneal cavity) is an infrequent problem that is very troublesome. Most cases are related to repeated fluid overload, poor nutrition, and cardiomyopathy. Although some patients overcome ascites, deterioration and death are frequent outcomes.
Hematologic system
What are the hematologic abnormalities?
Bleeding tendencies are seen as a result of a decrease in the quality and quantity of platelet production.
Anemia is the most common and severe hematologic defect. The hematocrit for normal men is 46% to 52%; for women it is 40% to 45%. People with uremia or who are on maintenance dialysis are anemic and have considerably lower hematocrit values. Anemia from diminished erythropoietin secretion occurs and results in fatigue, pallor, shortness of breath, and chest pain. The hostile uremic environment decreases the survival of red blood cells (RBCs) from 120 to 70 days.
What causes anemia?
Causes of anemia include (1) failure of production, or inhibition of action, of erythropoietin, a hormone produced by the kidney that stimulates the bone marrow to produce red blood cells; (2) a shortened life span of the red blood cells; (3) impaired intake of iron; (4) blood loss, including a tendency to bleed from the nose, gums, gastrointestinal tract, uterus, or skin, caused by platelet abnormalities; (5) blood loss related to the dialysis procedure itself; (6) elevated levels of parathyroid hormone (PTH), which has a suppressive effect on erythropoiesis in the bone marrow; and (7) poor nutrition and diet.
How does dialysis influence anemia?
Incomplete blood recovery after dialysis, dialyzer leaks, and frequent blood sampling contribute to anemia. The patient who is receiving adequate dialysis, is in a good nutritional state, and has adequate iron stores and intake will usually stabilize with a hematocrit between 20% and 30%. It is unusual for the hematocrit to go much higher except in people with polycystic kidney disease, in whom there may be greater than normal production of erythropoietin.
To minimize blood loss related to dialysis, particular care must be taken to (1) pretest dialyzers to prevent leaks; (2) monitor heparinization to prevent clotting; (3) return blood as completely as possible; (4) prevent damage to blood cells from incorrect pump occlusion or equipment malfunction; and (5) minimize the volume and number of blood samples drawn.
What symptoms does anemia produce in chronic kidney disease patients?
In CKD, the anemia has usually been present for many weeks or months, and patients become adjusted to it. As the hematocrit improves while patients are on dialysis, they begin to feel better. These people still have considerably fewer red blood cells than normal and become dyspneic and tire easily. Other symptoms attributable to anemia include poor exercise tolerance, weakness, sexual dysfunction, anorexia, and inability to think clearly.
Musculoskeletal system
How do the kidneys keep the bones healthy?
The kidneys keep the bones healthy by balancing the amount of calcium and phosphorus in the blood. Healthy kidneys produce a hormone called calcitriol, which enables the body to absorb calcium from the diet into the bloodstream.
During the progression of renal failure there is loss of ability to excrete phosphate. Phosphate ions accumulate in the body fluids and lead to a reciprocal decrease of serum calcium. The parathyroid glands seek to maintain a normal concentration of calcium in body fluid and respond by increasing production of PTH. This causes calcium to be resorbed from the bones, resulting in loss of bone density and strength. In addition, the active form of vitamin D, needed for normal bone metabolism, is manufactured in the kidney and is deficient in CKD patients. Dialysis does not fully correct the disordered calcium-phosphorus metabolism, and progressive renal osteodystrophy (the term used for several bony manifestations) is a serious problem for many patients (Fig. 5-1). Dialysis patients have a higher prevalance for hip fractures and bone loss.
Figure 5-1 Pathogenesis of renal osteodystrophy.
(From Lewis SM, Heitkemper MM, Dirksen SR: Medical-surgical nursing, ed 7, St. Louis, 2007, Mosby.)
What other factors are involved in the bone disorder?
The absorption of dietary calcium from the intestinal tract is decreased in CKD. There is resistance to the action of PTH, which normally enhances the resorption of calcium from bone. Chronic acidosis enhances calcium reabsorption from bone, further contributing to loss of bone density. In addition, the aluminum-containing phosphate-binding gels cause a form of renal bone disease. The aluminum in these gels is absorbed and deposited in bone, leading to a form of osteomalacia.
What are the bony changes seen in osteodystrophy?
The bony changes seen in osteodystrophy include adynamic bone, osteomalacia, osteitis fibrosa, osteoporosis, osteosclerosis, and growth retardation (in children); in addition, metastatic calcification occurs. Adynamic bone is bone with little or no metabolic activity; osteomalacia is deficient calcification of bone; osteitis fibrosa is excessive destruction of bone by osteoclasts, with replacement by fibrous tissue; osteoporosis is deficiency of both bone matrix and calcification; and osteosclerosis is abnormally dense bone. The term renal osteodystrophy spans the totality of these various bone diseases in the uremic patient.
Metastatic calcification results when the product of serum calcium multiplied by phosphorus (measured in milligrams per deciliter) is 75 or greater. One should therefore keep this calcium and phosphorus product below 70.
What symptoms does osteodystrophy cause?
Many patients complain of sore, painful feet or back pain. Fractures, when they occur, are painful and heal poorly. Metastatic calcification causes precipitates in soft tissue around joints. Less apparent, but more dangerous, are diffuse deposits of calcium in the heart muscle and in the lung. Itching may be intensified in the presence of a high calcium-phosphorus ratio. Skin ulcerations and gangrene of the tips of toes and fingers have occurred. Aggravation of hypertension is frequent.
How is osteodystrophy treated?
A priority system is necessary in the management of uremic osteodystrophy. The first objective is to maintain a low serum phosphorus to prevent metastatic calcification and hyperparathyroidism. The serum phosphorus level depends on intake, removal by dialysis, and binding of phosphate within the gastrointestinal tract. Restriction of dietary protein intake also limits phosphate intake. A variety of agents are available to bind phosphate to prevent absorption from the gastrointestinal tract. Those agents containing aluminum should be avoided and calcium-containing compounds should be used instead. Their activity depends on the surface area available for binding. The problem is to find the dose of phosphate binder that provides sufficient surface area throughout the day and is palatable enough for patient compliance. A change in medication periodically may make it more acceptable. Failure to bind phosphate adequately usually represents failure of the patient to take the phosphate binder.
When serum phosphate is lowered to about 4 mg/dL, elevation of serum calcium to greater than 10 mg/dL reduces the parathyroid stimulation of osteoclasts that causes osteitis fibrosa. One must be cautious, however, not to reduce the PTH level too much. Adynamic bone disease will occur if the PTH level is decreased to normal. The goal should be a PTH level between 1.5 and 3 times the upper limit of normal. Elevation of serum calcium can be achieved in several ways. The usual concentration of diffusible calcium in dialysis fluid is well above that of the serum, so each dialysis provides a surge of calcium. The administration of 1 to 2 g of calcium orally will often lead to an improved serum calcium level even in the absence of normal quantities of potent vitamin D compounds. If the desired level of serum calcium does not result from these efforts, 1,25-dihydroxycholecalciferol may be administered either orally or intravenously. Vitamin D may also be helpful in maintaining bone formation, apart from its role in the gastrointestinal absorption of calcium. Finally, do not forget that alleviation of chronic acidosis of uremia is another objective of treatment. Some patients will develop hypercalcemia on this regimen and will require a lower calcium level in the dialysis bath.
Even if the treatment is successful in maintaining a low serum phosphorus level and a high serum calcium level, some patients may persist with the problems of renal osteodystrophy. Those with bone pain are likely to have a component of adynamic bone or osteomalacia. Those with fractures and a high alkaline phosphatase may suffer to a large extent from osteitis fibrosa. Persistence of renal osteodystrophy, with x-ray film changes consistent with hyperparathyroidism, high PTH levels, and a high alkaline phosphatase, may warrant a parathyroidectomy: either a four-gland removal or a subtotal parathyroidectomy. A bone biopsy is advisable before parathyroidectomy.
What is calciphylaxis?
Calciphylaxis is a rare but potentially life-threatening complication that may occur in ESRD patients. The causes of calciphylaxis are poorly understood but usually the result of several comorbid factors. Hypercalcemia, hyperphosphatemia, and hyperparathyroidism all seem to be contributing factors in this condition.
When the serum phosphorus and the serum calcium levels become elevated together, insoluble calcium phosphate crystals develop. You will see this occur when the calcium and phosphorus product exceeds 70 mg/100 dL. These calcium phosphate crystals deposit in the soft tissues of the body, including lungs, joints, heart valves, cornea, and skin. Soft tissue calcifications usually affect the trunk and lower extremities but can occur in the breast, shoulder, or buttocks. Calciphylaxis usually begins as painful, purplish skin lesions that later form nodules. These nodules ulcerate and finally form eschar with underlying tissue necrosis. Blood flow is diminished to the tissue and the area eventually becomes necrotic. These lesions are difficult to heal and often become infected. Calciphylaxis is associated with a high mortality rate, with death occurring usually from sepsis from infected wounds or skin lesions. Prompt identification and treatment of this condition may help to diminish the morbidity and mortality associated with this disease.
What joint disorders occur as a result of chronic kidney disease?
Uric acid is frequently elevated in CKD patients. The hyperuricemia may be associated with a goutlike involvement of one or more joints. Occasionally there is a true gouty attack, but most episodes are of pseudogout. Dialysis amyloidosis (DA) may also be seen in long-term dialysis patients.
What is pseudogout?
Pseudogout is an acute inflammation, usually involving a single area at or near a joint. The back of the hand or wrist, finger joints, and shoulders are common locations. Pain comes on abruptly, followed rapidly by tenderness, swelling, and limitation of motion. This lasts three to five days or longer unless treated.
How can pseudogout be treated?
Colchicine or one of the nonsteroidal antiinflammatory agents often relieves distress in 24 to 36 hours.
Are there residual effects of pseudogout?
Soft tissue swelling may persist for several weeks. Areas of metastatic calcification at the site sometimes are seen on an x-ray examination.
Is there any preventive treatment for pseudogout?
Frequent dialyses usually keep the uric acid below serious levels. If a very high level of uric acid persists, use of allopurinol may be considered.
What is dialysis amyloidosis?
Amyloid is a peculiar form of protein that precipitates in various body tissues. There are many different kinds of amyloid, including amyloid composed of β2-microglobulin that is unique to dialysis patients. This protein is normally excreted by the kidneys, but is poorly dialyzed and therefore accumulates in the blood of patients with CKD. This protein then deposits in joints and periarticular structures of the shoulders, hands, wrist, neck, and elsewhere, causing pain and limitation of motion. If progressive, this can be extremely debilitating.
Who gets dialysis amyloidosis?
Patients on dialysis for long periods (more than three years) are prone to DA. The majority of patients on dialysis for more than 10 years will have DA. Patients dialyzed with high-flux synthetic membranes are less likely to experience this complication.
What is carpal tunnel syndrome?
Carpal tunnel syndrome (CTS) in dialysis patients is compression of the median nerve at the wrist by the carpal tunnel sheath, which has been thickened by deposition of amyloid. CTS causes pain, numbness, and tingling of the thumb and first two digits. Pain medications, nonsteroidal antiinflammatory drugs, and deep therapeutic ultrasound may ease joint symptoms. Renal transplantation usually causes a rapid disappearance of symptoms.
Neurologic system
What neurologic changes occur with uremia?
Fatigue, slow mental processes, anxiety, depression, and agitation are common with uremia. Seizures occur if azotemia increases rapidly. Sleep disturbances in the form of insomnia, restless leg movements, and sleep apnea are major concerns. Restless leg syndrome (RLS) causes the individual to have an uncontrollable urge to move the extremities in response to unpleasant sensations. The lower extremities are most often affected and the discomfort occurs usually when the patient is at rest. Movement helps to alleviate the symptoms. Symptoms occur most often in the evening and begin to diminish in the early morning. The causes of RLS are not precisely defined but might be associated with anemia. Electroencephalographic (EEG) changes (increased slow wave activity) occur and are related to increased PTH level. Calcium content of brain tissue is increased, and brain aluminum is elevated.
What is the potential for insomnia in this patient population?
Inability to sleep or fitful sleeping during the usual hours of rest is a common problem among dialysis patients. Often the patient sleeps throughout the dialysis procedure, and it may be that the need for sleep at other times is reduced. Other patients seem to have a pathologic inability to rest soundly. RLS, periodic leg movements during sleep, sleep apnea, and depression have been identified as contributing factors to the insomnia associated with CKD (Hopkins, 2005).
Response to sedatives and tranquilizers is usually poor and the risk of dependency is considerable. No adverse effects from the lack of sleep have been seen and it is suspected that the problem is most often one of fitful or interrupted sleep, which is interpreted as “no sleep.” Sleep apnea is more common in dialysis patients than in the general population. The reason for this is unclear, but formal sleep studies may be useful for selected patients.
What is dialysis dementia?
Dialysis dementia is a rare syndrome, first described in 1972. It may appear after a few months or after several years in patients who are seemingly well dialyzed and doing well. There is a peculiar complex of garbled speech (dyspraxia), asymmetric muscle jerking, mental deterioration, and seizures, along with characteristic EEG changes. A number of studies have implicated aluminum accumulation as a cause, primarily from administered aluminum hydroxide. With the use of calcium-containing phosphate binders in place of aluminum hydroxide, this syndrome has largely disappeared.
What is uremic neuropathy?
Neuropathy indicates deterioration of nerve function. It may develop gradually as renal failure progresses, or it may appear suddenly after an intercurrent infection or an episode of fluid overload. Peripheral neuropathy may present as burning feet, twitching, restless legs, reduced vibratory sensation, and decreased reflexes. The latter relate to slowed nerve conduction velocity, which is present in most dialysis patients. A motor neuropathy or myopathy may present as weakness of proximal muscles of arms and legs. Changes usually begin at the toes and progress upward. The upper extremities may be involved, but less often than the lower extremities.
Is neuropathy common?
Neuropathy, in subclinical or clinical form, has been reported in up to 80% of people with CKD. It is often seen at the time dialysis begins, possibly because that is when a careful search is done. Clinically significant neuropathy is less common with earlier institution of dialysis.
Can neuropathy be detected before symptoms appear?
Nerve conduction velocity measurements are used to detect and to quantitate progression or improvement of neuropathy. Most patients with moderately advanced azotemia have some delay in nerve conduction, often long before symptoms appear.
The test, although not difficult, is subject to many variables that make its reproducibility questionable and small changes difficult to evaluate.
Is neuropathy relieved by dialysis?
If dialysis is begun early, when only prolongation of conduction time is demonstrable, frequent dialysis may prevent worsening. More severe nerve damage responds very slowly to dialysis. If the amount and frequency of dialysis are not adequate, neuropathy may develop or, if already present, will worsen.
How does the dialysis prescription relate to neuropathy?
When adequate dialysis is prescribed and delivered (Kt/Vurea* ≥ 1.2, with protein catabolic rate [PCR] 1 g/kg/day), neuropathy is rarely seen. If it does develop, it strongly suggests that underdialysis and urea kinetic modeling should be performed to assess this. Even if the modeling parameters fall within an acceptable range, worsening neuropathy requires intensification of the dialysis procedure (larger dialyzer, more time, higher blood flow).
What is the cause of neuropathy?
The cause of neuropathy is not known. The pathologic changes in the nerves are similar to those seen in some cases of diabetes mellitus, in certain vitamin deficiency states, and in chronic alcoholism. A number of authorities believe that neuropathy results from accumulated medium- to large-size toxic metabolites in the body. However, specific toxic agents have not been identified.
Is there involvement of nerves other than the peripheral nerves?
A few patients develop deafness, for which no other cause can be demonstrated. Other patients on dialysis have developed gastric atony or bowel dysfunction resembling the autonomic disturbances seen in some diabetic individuals. Impotence may also be related to uremic toxin accumulation.
Respiratory system
What respiratory problems are seen in the patient with chronic kidney disease?
Pulmonary edema from excess fluid accumulation and left ventricular dysfunction may occur and are seen more frequently in the patient with acute renal failure. The incidence of tuberculosis is estimated to be as much as tenfold higher in the hemodialysis population as compared with the general population (Daugirdas, Blake, & Ing, 2007). Kussmaul respirations may be seen in the patient with metabolic acidosis. The body will compensate by increasing the rate and depth of respirations in an effort to excrete excess carbon dioxide.
What is metabolic acidosis?
Metabolic acidosis is a condition that occurs when excess hydrogen ions build up in the blood. Initially, buffers in the blood combine with the excess hydrogen ions and there are no symptoms. As the number of hydrogen ions increases, fewer buffers are available to bind with these ions. The pH of the blood then lowers and the patient will respond physically to help eliminate the excess hydrogen ions. Under normal conditions the kidneys would eliminate more hydrogen ions in the urine to compensate.
Reproductive system
Does chronic dialysis contribute to menstrual dysfunction?
Women commonly experience cessation of menstruation as part of the uremic syndrome and by the time they require maintenance dialysis. A few pregnancies in women on maintenance dialysis have been reported. Other reports suggest that less than 20% of such women of childbearing age ovulate at all. Most are amenorrheic or have oligomenorrhea of an anovulatory nature. Hypermenorrhagia may develop in some women after the initiation of dialysis, requiring treatment for the large blood losses. To prevent unnecessary (undesirable) blood loss, patients should be instructed to report any abnormal or excessive menstrual flow. Early detection of the problem may eliminate the need for surgical intervention.
A significant proportion of women on maintenance dialysis are troubled by galactorrhea. Endocrine studies suggest a defect at the hypothalamic-pituitary level, such that the hormonal feedback mechanisms do not function normally.
What about infertility?
Infertility, in both the male and the female patient on maintenance dialysis, is very common. Research studies indicate poor sperm formation in most men. The exact mechanism is less clear in women, but as indicated previously is presumed to be endocrine in nature.
What other sexual problems have been associated with chronic dialysis?
Sexual dysfunction is a very real problem for most maintenance dialysis patients. Reduction of libido and impotence in men is common as uremia develops. Various sociologic and psychologic studies, depending largely on questionnaire responses, have suggested that total or partial impotence is a problem in 60% of men receiving maintenance dialysis. However, another study suggests that 50% to 70% of the impotence among male dialysis patients has an organic basis—whether neuropathic, endocrine, or vascular is unknown. In addition, medication (particularly antihypertensive agents) must always be considered a potential cause of impotence.
The reproductive problems described previously are often relieved after correction of anemia with Epogen. The mechanism for this is unclear, but several successful pregnancies in women receiving Epogen have now been reported.
Metabolic disturbances
Uremia is associated with abnormal metabolism of glucose, lipids, and protein.
How does chronic kidney disease affect glucose metabolism?
Nondiabetics with CKD have abnormal glucose metabolism. Cellular sensitivity to insulin is reduced. After a glucose load, peak blood sugar is near normal, but the rate of decline is slow.
When CKD stage 5 is the result of type 1 diabetes mellitus (onset before age 35), peripheral cellular resistance to insulin is especially severe. Violent swings between hypo- and hyperglycemia are frequent. Total insulin needs decrease somewhat after the patient begins dialysis, but wide swings of blood glucose and problems with insulin dosage continue because of the decreased ability of the kidney to metabolize insulin and the consequent increase in the half-life of insulin.
Most diabetic CKD in the U.S. is the result of type 2 diabetes. Such patients are usually obese and have a resistance to insulin. Most diabetic symptoms are improved by weight reduction and increased activity. Many patients respond to oral hypoglycemic agents.
Does chronic kidney disease affect lipid metabolism?
Type 4 hyperlipoproteinemia is common. The elevated very-low-density lipoproteins (VLDLs) are somewhat different from the usual VLDLs, which may be a result of reduced hepatic lipoprotein lipase activity, possibly related to insulin resistance. Carnitine deficiency has also been suggested to have a role.
How is protein metabolism affected by chronic kidney disease?
Protein calorie malnutrition is common. Loss of lean tissue mass is masked by an increase in body water with occult edema. Serum albumin tends to be low because of poor protein intake, although impaired hepatic synthesis may play a part. Several nonessential amino acids are elevated, and certain essential polypeptides are decreased.
What other endocrine abnormalities occur with uremia?
Changes in insulin production and effect, and PTH perturbations have been mentioned as additional endocrine abnormalities. Most other endocrine systems are also affected by uremia. These include the following:
• Plasma norepinephrine levels are increased; epinephrine values are inconsistent.
• Cortisol levels are near normal, with a normal response to adrenocorticotropic hormone (ACTH). Aldosterone is increased.
• Both glucagon and gastrin values are elevated. This results from loss of renal metabolic clearance.
• Hypothyroidism is more frequent in CKD patients than in the general population. Euthyroid individuals on dialysis have low total thyroxine (T4) and triiodothyronine (T3) values and reduced free T3, whereas free T4 is normal. Conversion of T4 to T3 in peripheral tissue is reduced. Thyroid-binding globulin is low. Thyroid-stimulating hormone (TSH) is mostly normal, but the response to thyroid-releasing hormone is reduced.
• Besides ACTH and TSH, the anterior pituitary produces four other hormones that are affected by uremia. Growth hormone and prolactin are increased. There is both increased production and decreased elimination. No systemic effect has been attributed to the elevation of either hormone.
Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) each have critical roles in the pituitary-gonadal axis in both sexes. Production of abnormal estrogen and progesterone, or testosterone, by the gonads in uremia adversely influences the feedback mechanisms to the pituitary gland. LH levels are elevated in both men and women. FSH values are normal or minimally increased in both sexes. End effects include testicular atrophy, low sperm count, and impotence in men, and dysmenorrhea or amenorrhea in women. Infertility is usual for both men and women. There is accumulating evidence that patients receiving recombinant human erythropoietin have fewer sexual problems of this sort. Much of the data are subjective. A number of objective studies support reductions of prolactin and growth hormone after administration of erythropoietin, but the mechanism is not clear. It is also unclear whether the effects that have been noted are the result of correction of anemia or are due to some specific effect of erythropoietin.
* Kt/Vurea is a way to measure the dialysis dose. The measurement takes into account the dialyzer efficiency (K), the treatment time (t), and the total volume of urea in the body (Vurea).