Manifestation and Management of Renal Failure Conditions in France

Renal failure is a condition in which the kidneys fail to remove metabolic end products from the blood and regulate the fluid, electrolyte, and pH balance of the extracellular fluids. The underlying cause may be renal disease, systemic disease, or urologic defects of non-renal origin. Renal failure can occur as an acute or a chronic disorder. Acute renal failure is abrupt in onset and often is reversible if recognized early and treated appropriately. In contrast, chronic renal failure is the end result of irreparable damage to the kidneys. It develops slowly, usually over the course of a number of years.

Stages of Progression

The rate of nephron destruction differs from case to case, ranging from several months to many years. The progression of chronic renal failure usually occurs in four stages: diminished renal reserve, renal insufficiency, renal failure, and end-stage renal disease.

Diminished Renal Reserve

Diminished renal reserve occurs when the GFR drops to approximately 50% of normal. At this point, the serum BUN and creatinine levels still are normal, and no symptoms of impaired renal function are evident. This is supported by the fact that many persons survive an entire lifetime with only one kidney. Because of the diminished reserve, the risk for development of azotemia increases with an additional renal insult, such as that caused by nephrotoxic drugs.

Renal Insufficiency

Renal insufficiency represents a reduction in the GFR to 20% to 50% of normal. During this stage, azotemia, anemia, and hypertension appear. Signs and symptoms of renal insufficiency do not begin to appear until more than 50% of the function in both kidneys is lost. As nephrons are destroyed, the remaining nephrons compensate for those that are lost by filtering more solute particles from the blood. Because the solute particles are osmotically active, they cause additional water to be lost in the urine. One of the earliest symptoms of renal insufficiency is isosthenuria or polyuria with urine that is almost isotonic with plasma. Conservative treatment during this stage includes measures to retard the deterioration of renal function and assist the body in managing the effects of impaired function. Because the kidneys have difficulty eliminating the waste products of protein metabolism, a restricted protein diet usually produces fewer symptoms and slows progression of renal failure. The few remaining nephrons that constitute the functional reserve of the kidneys can be easily disrupted; at that point, renal failure progresses rapidly.

Renal Failure

Renal failure develops when the GFR is less than 20% of normal. At this point, the kidneys cannot regulate volume and solute composition, and edema, metabolic acidosis, and hyperkalemia develop. These alterations affect other body systems to cause neurologic, gastrointestinal, and cardiovascular manifestations.

End-Stage Renal Disease

End-stage renal disease (ESRD) occurs when the GFR is less than 5% of normal. Histologic findings of an end-stage kidney include a reduction in renal capillaries and scarring in the glomeruli. Atrophy and fibrosis are evident in the tubules. The mass of the kidneys usually is reduced. At this final phase of renal failure, treatment with dialysis or transplantation is necessary for survival.

Clinical Manifestations

The clinical manifestations of renal failure include alterations in water, electrolyte, and acid-base balance; mineral and skeletal disorders; anemia and coagulation disorders; hypertension and alterations in cardiovascular function; gastrointestinal disorders; neurologic complications; disorders of skin integrity; and immunologic disorders. Uremia, which literally means “urine in the blood,” is the term used to describe the clinical manifestations of ESRD. Uremia differs from azotemia, which merely indicates the accumulation of nitrogenous wastes in the blood and can occur without symptoms.

There currently are four target populations that comprise the entire population of persons with chronic renal failure: persons with chronic renal insufficiency, those with ESRD being treated with hemodialysis, those being treated with peritoneal dialysis, and renal transplant recipients. The manifestations of renal failure are determined largely by the extent of renal function that is present (e.g., renal insufficiency, ESRD), coexisting disease conditions, and the type of renal replacement therapy the person is receiving.


Disorders of Neural Function

Many persons with chronic renal failure have alterations in peripheral and central nervous system function. Peripheral neuropathy, or involvement of the peripheral nerves, affects the lower limbs more frequently than the upper limbs. It is symmetric and affects both sensory and motor function. Neuropathy is caused by atrophy and demyelination of nerve fibers, possibly caused by uremic toxins. Restless legs syndrome is a manifestation of peripheral nerve involvement and can be seen in as many as two thirds of patients on dialysis. This syndrome is characterized by creeping, prickling, and itching sensations that typically are more intense at rest. Temporary relief is obtained by moving the legs. A burning sensation of the feet, which may be followed by muscle weakness and atrophy, is a manifestation of uremia.

The central nervous system disturbances in uremia are similar to those caused by other metabolic and toxic disorders. Sometimes referred to as uremic encephalopathy, the condition is poorly understood and may result, at least in part, from an excess of toxic organic acids that alter neural function. Electrolyte abnormalities, such as sodium shifts, also may contribute. The manifestations are more closely related to the progress of the uremic disorder than to the level of the metabolic end products. Reductions in alertness and awareness are the earliest and most significant indications of uremic encephalopathy.

This often is followed by an inability to fix attention, loss of recent memory, and perceptual errors in identifying persons and objects. Delirium and coma occur late in the course; seizures are the preterminal event. Disorders of motor function commonly accompany the neurologic manifestations of uremic encephalopathy. During the early stages, there often is difficulty in performing fine movements of the extremities; the gait becomes unsteady and clumsy with tremulousness of movement. Asterixis (dorsiflexion movements of the hands and feet) typically occurs as the disease progresses. It can be elicited by having the person hyperextend his or her arms at the elbow and wrist with the fingers spread apart. If asterixis is present, this position causes side-to-side flapping movements of the fingers.

Disorders of Skin Integrity

Skin manifestations are common in persons with ESRD. The skin often is pale because of anemia and may have a sallow, yellow-brown hue. The skin and mucous membranes often are dry, and subcutaneous bruising is common. Skin dryness is caused by a reduction in perspiration caused by the decreased size of sweat glands and the diminished activity of oil glands. Pruritus is common; it results from the high serum phosphate levels and the development of phosphate crystals that occur with hyperparathyroidism. Severe scratching and repeated needlesticks, especially with hemodialysis, break the skin integrity and increase the risk for infection. In the advanced stages of untreated renal failure, urea crystals may precipitate on the skin as a result of the high urea concentration in body fluids. The fingernails may become thin and brittle, with a dark band just behind the leading edge of the nail, followed by a white band. This appearance is known as Terry’s nails.

Sexual Dysfunction

Alterations in physiologic sexual responses, reproductive ability, and libido are common. The cause probably is multifactorial and may result from high levels of uremic toxins, neuropathy, altered endocrine function, psychological factors, and medications (e.g., antihypertensive drugs). Impotence occurs in as many as 56% of male patients receiving dialysis. Derangements of the pituitary and gonadal hormones, such as decreases in testosterone levels and increases in prolactin and luteinizing hormone levels, are common and cause erectile difficulties and decreased spermatocyte counts. Loss of libido may result from chronic anemia and decreased testosterone levels. Several drugs, such as exogenous testosterone and bromocriptine, have been used in an attempt to return hormone levels to normal.
Impaired sexual function in women is manifested by abnormal levels of progesterone, luteinizing hormone, and prolactin. Hypofertility, menstrual abnormalities, decreased vaginal lubrication, and various orgasmic problems have been described. Amenorrhea is common among women who are receiving dialysis therapy.

Altered Immune Function

Infection is a common complication and cause of hospitalization and death of patients with chronic renal failure. Immunologic abnormalities decrease the efficiency of the immune response to infection. All aspects of inflammation and immune function may be affected adversely by the high levels of urea and metabolic wastes, including a decrease in granulocyte count, impaired humoral and cell-mediated immunity, and defective phagocyte function. The acute inflammatory response and delayed-type hypersensitivity response are impaired. Although persons with ESRD have normal humoral responses to vaccines, a more aggressive immunization program may be needed. Skin and mucosal barriers to infection also may be defective. In persons who are receiving dialysis, vascular access devices are common portals of entry for pathogens. Many persons with ESRD do not experience fever with infection, making the diagnosis more difficult.

Elimination of Drugs

The kidneys are responsible for the elimination of many drugs and their metabolites. Renal failure and its treatment can interfere with the absorption, distribution, and elimination of drugs. The administration of large quantities of phosphate binding antacids to control hyper phosphatemia and hypocalcemia in patients with advanced renal failure interferes with the absorption of some drugs. Many drugs are bound to plasma proteins, such as albumin, for transport in the body; the unbound portion of the drug is available to act at the various receptor sites and is free to be metabolized. A decrease in plasma proteins, particularly albumin, that occurs in many persons with ESRD results in less protein-bound drug and greater amounts of free drug.

Diagnosis and Treatment

Given the high morbidity and mortality rates associated with acute renal failure, attention should be focused on prevention and early diagnosis. This includes assessment measures to identify persons at risk for the development of acute renal failure, including those with pre-existing renal insufficiency and diabetes. Elderly persons are susceptible to all forms of acute renal failure because of the effects of aging on renal reserve. Careful observation of urine output is essential for persons
at risk for the development of acute renal failure. Urine output and urine osmolality or specific gravity should be carefully monitored. One of the earliest manifestations of tubular damage is the inability to concentrate the urine. Further diagnostic information that can be obtained from the urinalysis includes evidence of proteinuria, hemoglobinuria, and casts or crystals in the urine. Blood tests for BUN and creatinine provide information regarding the ability to remove nitrogenous wastes from the blood.

A major concern in the treatment of acute renal failure is identifying and correcting the cause (e.g., improving renal perfusion, discontinuing nephrotoxic drugs). Fluids are carefully regulated in an effort to maintain normal fluid volume and electrolyte concentrations. Adequate caloric intake is needed to prevent the breakdown of body proteins, which increases the need for elimination of nitrogenous wastes. Parenteral hyperalimentation may be used for this purpose. Because secondary infections are a major cause of death in persons with acute renal failure, constant effort is needed to prevent and treat such infections. Dialysis or continuous renal replacement therapy (CRRT) may be indicated when nitrogenous wastes and the water and electrolyte balance cannot be kept under control by other means.

In summary, chronic renal failure results from the destructive effects of many forms of renal disease. Regardless of the cause, the consequences of nephron destruction in ESRD are alterations in the filtration, reabsorption, and endocrine functions of the kidneys. The progression of chronic renal failure usually occurs in four stages: diminished renal reserve, renal insufficiency, renal failure, and ESRD. Renal insufficiency represents a reduction in the GFR to approximately 20% to 50% of normal; renal failure, a reduction to less than 20% to 25% of normal; and ESRD, a decrease in GFR to less than 5% of normal.

End-stage renal disease affects almost every body system. It causes an accumulation of nitrogenous wastes (i.e., azotemia), alters sodium and water excretion, and alters regulation of body levels of potassium, phosphate, calcium, and magnesium. It also causes skeletal disorders, anemia, and alterations in cardiovascular function, neurologic disturbances, gastrointestinal dysfunction, and discomforting skin changes. The treatment of ESRD can be divided into two types: conservative management of renal insufficiency and renal replacement therapy with dialysis or transplantation. Conservative treatment consists of measures to prevent or retard deterioration in remaining renal function and to assist the body in compensating for the existing impairment.