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CHAPTER
35
Disorders of Renal Function
CONGENITAL DISORDERS OF THE KIDNEYS
Agenesis and Hypoplasia
Alterations in Kidney Position and Form
Cystic Disease of the Kidney
Simple and Acquired Renal Cysts
Medullary Cystic Disease
Polycystic Kidney Disease
OBSTRUCTIVE DISORDERS
Mechanisms of Renal Damage
Manifestations
Diagnosis and Treatment
Renal Calculi
Types of Stones
Manifestations
Diagnosis and Treatment
URINARY TRACT INFECTIONS
Etiologic Factors
Host–Agent Interactions
Obstruction and Reflux
Catheter-Induced Infection
Manifestations
Diagnosis and Treatment
Diagnosis
Treatment
Infections in Special Populations
Urinary Tract Infections in Women
Urinary Tract Infections in Children
Urinary Tract Infections in the Elderly
DISORDERS OF GLOMERULAR FUNCTION
Mechanisms of Glomerular Injury
Specific Types of Glomerular Disease
Acute Proliferative Glomerulonephritis
Rapidly Progressive Glomerulonephritis
Nephrotic Syndrome
Immunoglobulin A Nephropathy
Chronic Glomerulonephritis
Glomerular Lesions Associated With Systemic Disease
Diabetic Glomerulosclerosis
Hypertensive Glomerular Disease
TUBULOINTERSTITIAL DISORDERS
Renal Tubular Acidosis
Pyelonephritis
Acute Pyelonephritis
Chronic Pyelonephritis
Drug-Related Nephropathies
NEOPLASMS
Wilms’ Tumor
Adult Kidney Cancer
M
ore than 20 million North Americans, or one in
nine adults, have chronic kidney disease.1 Kidney
and urologic disease continue to be major causes of
work loss, physician visits, and hospitalizations among
men and women. Each year, kidney stones result in 1 million physician office visits and 300,000 hospitalizations,
and urinary tract infections (UTIs) result in 8.3 million office visits and 1.6 million hospitalizations.1
The kidneys are subject to many of the same types of
disorders that affect other body structures, including developmental defects, infections, altered immune responses,
and neoplasms. The kidneys filter blood from all parts of
the body, and although many forms of kidney disease originate in the kidneys, others develop secondary to disorders
such as hypertension, diabetes mellitus, and systemic lupus
erythematosus (SLE). The content in this chapter focuses
on congenital disorders of the kidneys, obstructive disorders, UTIs, disorders of glomerular function, tubulointerstitial disorders, and neoplasms of the kidneys. Acute and
chronic renal failure is discussed in Chapter 36
Congenital Disorders of the Kidneys
After completing this section of the chapter, you should be able to
meet the following objectives:
✦ Define the terms agenesis, dysgenesis, and hypoplasia as
they refer to the development of the kidney
✦ Cite the effect of urinary obstruction in the fetus
✦ Describe the genetic basis for renal cystic disease, the
pathology of the disorder, and its signs and symptoms
809
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Some abnormality of the kidneys and ureters occurs in
approximately 3% to 4% of newborn infants.2 Anomalies
in shape and position are the most common. Less common
are disorders involving a decrease in renal mass (e.g., agenesis, hypogenesis) or a change in renal structure (e.g., renal
cysts). Many fetal anomalies can be detected before birth
by ultrasonography. In the normal fetus, the kidneys can
be visualized as early as 12 weeks.
AGENESIS AND HYPOPLASIA
The kidneys begin to develop early in the fifth week of
gestation and start to function approximately 3 weeks
later. Formation of urine is thought to begin in the 9th to
12th weeks of gestation; by the 32nd week, fetal production
of urine reaches approximately 28 mL/hour.3 Urine is the
main constituent of amniotic fluid. The relative amount of
amniotic fluid can provide information about the status of
fetal renal function. In pregnancies that involve infants
with nonfunctional kidneys or outflow obstruction of urine
from the kidneys, the amount of amniotic fluid is small—a
condition called oligohydramnios. The condition causes compression of the developing fetus and is often associated with
impaired development of fetal structures.2
The term dysgenesis refers to a failure of an organ to develop normally. Agenesis is the complete failure of an
organ to develop. Total agenesis of both kidneys is incompatible with extrauterine life. Infants are stillborn or die
shortly after birth of pulmonary hypoplasia. Newborns
with renal agenesis often have characteristic facial features, termed Potter’s syndrome.4 The eyes are widely separated and have epicanthic folds, the ears are low set, the
nose is broad and flat, the chin is receding, and limb defects often are present.4,5 Other causes of neonatal renal
failure with the Potter phenotype include cystic renal
dysplasia, obstructive uropathy, and autosomal recessive
polycystic disease. Unilateral agenesis is an uncommon
anomaly that is compatible with life if no other abnormality is present. The opposite kidney usually is enlarged
as a result of compensatory hypertrophy.
In renal hypoplasia, the kidneys do not develop to normal size. Like agenesis, hypoplasia more commonly affects
only one kidney. When both kidneys are affected, there is
progressive development of renal failure. It has been suggested that true hypoplasia is extremely rare; most cases
probably represent acquired scarring due to vascular, infectious, or other kidney diseases rather than an underlying developmental failure.5,6
One of the most common alterations in kidney form
is an abnormality called a horseshoe kidney. This abnormality occurs in approximately 1 of every 500 to 1000 persons.4,5 In this disorder, the upper or lower poles of the
two kidneys are fused, producing a horseshoe-shaped structure that is continuous along the midline of the body
anterior to the great vessels. Most horseshoe kidneys are
fused at the lower pole6 (Fig. 35-1). The condition usually
does not cause problems unless there is an associated defect
in the renal pelvis or other urinary structures that obstructs
urine flow.
CYSTIC DISEASE OF THE KIDNEY
Renal cysts are fluid-filled sacs or segments of a dilated
nephron. The cysts may be single or multiple and can vary
in size from microscopic to several centimeters in diameter. There are four basic types of renal cystic disease: polycystic kidney disease, medullary sponge kidney, acquired
cystic disease, and simple kidney cysts. Although some
types of cysts are not congenital, they are included in this
section.
Renal cystic disease is thought to result from tubular
obstructions that increase intratubular pressure or from
changes in the basement membrane of the renal tubules
that predispose to cystic dilatation. After a cyst begins to
form, continued fluid accumulation contributes to its persistent growth. Renal cystic diseases probably exert their
effects by compressing renal blood vessels, producing degeneration of functional renal tissue and obstructing tubular flow.
ALTERATIONS IN KIDNEY POSITION
AND FORM
The development of the kidneys during embryonic life can
result in kidneys that lie outside their normal position,
usually just above the pelvic brim or within the pelvis. Because of the abnormal position, kinking of the ureters and
obstruction of urine flow may occur.
FIGURE 35-1 Horseshoe kidney. The kidneys are fused at the lower
poles. (Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 865].
Philadelphia: Lippincott-Raven)
CHAPTER 35
Simple and Acquired Renal Cysts
Simple cysts are a common disorder of the kidney. The
cysts may be single or multiple, unilateral or bilateral, and
they usually are less than 1 cm in diameter, although they
may grow larger. Most simple cysts do not produce signs
or symptoms or compromise renal function. When symptomatic, they may cause flank pain, hematuria, infection,
and hypertension related to ischemia-produced stimulation of the renin-angiotensin system. They are most common in older persons. Although the cysts are benign, they
may be confused clinically with renal cell carcinoma.
An acquired form of renal cystic disease occurs in persons with end-stage renal failure who have undergone prolonged dialysis treatment. The cysts, which measure 0.2 to
2 cm in diameter, probably develop as a result of tubular
obstruction.5 Although the condition is largely asymptomatic, the cysts may bleed, causing hematuria. Tumors,
usually adenomas but occasionally adenosarcomas, may
develop in the walls of these cysts.
Medullary Cystic Disease
Two major types of cystic disease involve the medullary
portion of the kidney: medullary sponge kidney and
nephronophthisis–medullary cystic disease complex.5,6
Medullary sponge kidney is characterized by small (<5 mm
in diameter), multiple cystic dilations of the collecting
ducts of the medulla. The disorder does not cause progressive renal failure; it does, however, produce urinary stasis
and predisposes to kidney infections and kidney stones.
The disease usually is asymptomatic in young adults. Symptomatic disease usually develops between the ages of 30
and 60 years, when affected persons begin to have flank
pain, dysuria, hematuria, and “gravel” in the urine as a result of stone formation in the cysts.6
Nephronophthisis–medullary cystic disease complex is a
group of related diseases characterized by renal medullary
cysts, sclerotic kidneys, and renal failure. Approximately
85% of cases have a hereditary basis. Symptoms usually develop during childhood, and the disorder accounts for
10% to 20% of renal failure in children. Polyuria, polydipsia, and enuresis (bed-wetting), which are early manifestations of the disorder, reflect impaired ability of the kidneys
to concentrate urine.5,6
Polycystic Kidney Disease
The most common form of renal cystic disease is polycystic kidney disease, which is the result of a hereditary trait.
It is one of the most common hereditary diseases in the
United States, affecting more than 600,000 Americans.1
There are two types of inherited polycystic disease: autosomal recessive and autosomal dominant.
Autosomal Recessive Polycystic Kidney Disease.
Autosomal recessive polycystic kidney disease, which is
present at birth, is rare compared with the adult variety.5,6
The disorder is inherited as a recessive trait, meaning that
both parents are carriers of the gene and that there is a one
in four chance of the parents having another child with
the disorder. Because the condition is present at birth, it
Disorders of Renal Function
811
formerly was called infantile or childhood polycystic disease.
The condition is bilateral, and significant renal dysfunction usually is present, accompanied by variable degrees of
liver fibrosis and portal hypertension. The disorder can be
diagnosed by ultrasonography.
There is no known treatment for the disease. Approximately 75% of infants die in the perinatal period, often
because the large kidneys compromise expansion of the
lungs.6 Some children may present with less severe kidney
problems and more severe liver disease.
Autosomal Dominant Polycystic Kidney Disease. Autosomal dominant polycystic kidney disease (ADPKD), also
called adult polycystic kidney disease, is a systemic disorder
that primarily affects the kidneys. The disease, which is inherited as an autosomal trait, results in the formation of
fluid-filled cysts in both kidneys with the threat of progression to chronic renal failure. Other manifestations of
the disease include hypertension, cardiovascular abnormalities, cerebral aneurysms, and cyst formation in other
organs such as the liver and pancreas.
Two mutant genes have been implicated in most cases
of the disorder.5–8 A polycystic kidney disease gene called
PKD1, located on chromosome 16, is responsible for approximately 85% of cases. It encodes a large membrane
protein called polycystin 1 that has domains similar to proteins involved in cell-to-cell and cell-to–extracellular matrix interactions. A second gene, called PKD2, is located on
chromosome 4. It encodes for a product called polycystin 2,
which is an integral membrane protein that is similar to
certain calcium and sodium channel proteins as well as a
portion of polycystin 1. Although the two mutations produce almost identical disease phenotypes, disease progression is typically more rapid in people with ADPKD type 1
disease than those with ADPKD type 2 disease.7,8
The link between the genetic defect in the polycystin
proteins and the formation of the fluid-filled cysts in the
kidney has not been fully established. It is thought that the
membrane proteins may play a role in cell-to-cell matrix
interactions that are important in tubular epithelial cell
growth and differentiation.5 Accordingly, it is hypothesized
that cysts develop as a result of an abnormality in cell differentiation, increased transepithelial fluid secretion, and
formation of an abnormal extracellular matrix that allows
the cyst to grow and separate from adjacent tubules. In addition, cyst fluids have been shown to harbor mediators
that enhance fluid secretion and induce inflammation, resulting in further enlargement of the cysts and the interstitial fibrosis that is characteristic of progressive polycystic
kidney disease.
It is interesting to note that although the mutant
ADPKD gene is present in all tubular cells of affected persons, cysts develop in only some tubules. Progression of
the disease is characterized by tubular dilatation with cyst
formation interspersed among normally functioning
nephrons. Fluid collects in the cyst while it is still part of
the tubular lumen, or it is secreted into the cyst after it has
separated from the tubule. As the fluid accumulates, the
cysts gradually increase in size, with some becoming as
large as 5 cm in diameter.5,6 The kidneys of persons with
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Renal Function
polycystic kidney disease eventually become enlarged because of the presence of multiple cysts (Fig. 35-2). Cysts
also may be found in the liver and, less commonly, the
pancreas and spleen. Mitral valve prolapse and other valvular heart diseases occur in 20% to 25% of persons, but are
largely asymptomatic. Most persons with polycystic disease also have colonic diverticula. One of the most devastating extrarenal manifestations is a weakness in the walls
of the cerebral arteries that can lead to aneurysm formation. Approximately 20% of persons with polycystic kidney
disease have an associated aneurysm, and subarachnoid
hemorrhage is a frequent cause of death.6
The manifestations of ADPKD include pain from the
enlarging cysts that may reach debilitating levels, episodes of gross hematuria from bleeding into a cyst, infected cysts from ascending UTI, and hypertension resulting from compression of intrarenal blood vessels with
activation of the renin-angiotensin mechanism.9,10 Renal
colic caused by kidney stones occurs in about 20% of persons with ADPKD.10 The progress of the disease is slow,
and end-stage renal disease is uncommon before 40 years
of age.
Ultrasound usually is the preferred technique for diagnosis of symptomatic patients and for screening of
asymptomatic family members.9 The ability to detect cysts
increases with age; 80% to 90% of affected persons older
than age 20 have detectable cysts. Computed tomography
(CT) may be used for detection of small cysts. Genetic linkage studies are now available for diagnosis of ADPKD, but
are usually reserved for cases in which radiographic imaging is negative and the need for a definitive diagnosis is
essential, such as when screening family members for potential kidney donation.9
The treatment of ADPKD is largely supportive and
aimed at delaying the progression of the disease. Control
of hypertension and prevention of ascending urinary tract
infections are important. Pain is a common complaint of
persons with ADPKD, and a systematic approach is needed
to differentiate the etiology of the pain and define an approach for management.10 Dialysis and kidney transplantation are reserved for those who progress to end-stage
renal disease.
In summary, approximately 10% of infants are born with potentially significant malformations of the urinary system. These
abnormalities can range from bilateral renal agenesis, which
is incompatible with life, to hypogenesis of one kidney, which
usually causes no problems unless the function of the remaining kidney is impaired. The developmental process can result
in kidneys that lie outside their normal position. Because of the
abnormal position, kinking of the ureters and obstruction of
urine flow can occur.
Renal cystic disease is a condition in which there is dilatation of tubular structures with cyst formation. Cysts may be single or multiple. Polycystic kidney disease is an inherited form
of renal cystic disease; it can be inherited as an autosomal recessive or an autosomal dominant trait. Autosomal recessive
polycystic kidney disease is rare and usually presents as severe renal dysfunction during infancy. Autosomal dominant
polycystic disease usually does not become symptomatic until
later in life, often after 40 years of age. The disease, which involves mutations in a polycystin gene, results in the formation
of fluid-filled cysts in both kidneys with the threat of progression to chronic renal failure. Other manifestations of the disease include hypertension, cardiovascular abnormalities,
cerebral aneurysms, and cysts in other organs such as the liver
and pancreas.
Obstructive Disorders
After completing this section of the chapter, you should be able to
meet the following objectives:
✦ List common causes of urinary tract obstruction
✦ Describe the effects of urinary tract obstruction on renal
structure and function
✦ Cite three theories that are used to explain the formation
of kidney stones
✦ Explain the mechanisms of pain and infection that occur
with kidney stones
✦ Describe methods used in the diagnosis and treatment of
kidney stones
FIGURE 35-2 Adult polycystic disease. The kidney is enlarged, and
the parenchyma is almost entirely replaced by cysts of varying size.
(Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 867]. Philadelphia:
Lippincott-Raven)
Urinary obstruction can occur in persons of any age
and can involve any level of the urinary tract from the urethra to the renal pelvis (Fig. 35-3). The conditions that
cause urinary tract obstruction include developmental
defects, calculi (i.e., stones), pregnancy, benign prostatic
hyperplasia, scar tissue resulting from infection and inflammation, tumors, and neurologic disorders such as spinal cord injury. The causes of urinary tract obstructions are
summarized in Table 35-1.
CHAPTER 35
Kidney
stone
Pregnancy
or tumor
Scar
tissue
Ureterovesicle
junction
stricture
Neurogenic
bladder
Bladder
outflow
obstruction
FIGURE 35-3 Locations and causes of urinary tract obstruction.
MECHANISMS OF RENAL DAMAGE
The destructive effects of urinary obstruction on kidney
structures are determined by the degree (i.e., partial vs.
complete, unilateral vs. bilateral) and the duration of the
obstruction. The two most damaging effects of urinary obstruction are stasis of urine, which predisposes to infection
and stone formation, and development of backpressure,
which interferes with renal blood flow and destroys kidney tissue.
TABLE 35-1
Causes of Urinary Tract Obstruction
Level of Obstruction
Cause
Renal pelvis
Renal calculi
Papillary necrosis
Renal calculi
Pregnancy
Tumors that compress the ureter
Ureteral stricture
Congenital disorders of the
ureterovesical junction and
ureteropelvic junction strictures
Bladder cancer
Neurogenic bladder
Bladder stones
Prostatic hyperplasia or cancer
Urethral strictures
Congenital urethral defects
Ureter
Bladder and urethra
Disorders of Renal Function
813
A common complication of urinary tract obstruction
is infection. Stagnation of urine predisposes to infection,
which may spread throughout the urinary tract. When
present, urinary calculi serve as foreign bodies and contribute to the infection. Once established, the infection is
difficult to treat. It often is caused by urea-splitting organisms (e.g., Proteus, staphylococci) that increase ammonia
production and cause the urine to become alkaline.11 Calcium salts precipitate more readily in stagnant alkaline
urine; thus, urinary tract obstructions also predispose to
stone formation.
In situations of marked or complete obstruction, backpressure develops because of a combination of continued
glomerular filtration and impedance to urinary flow. Prolonged or severe partial obstruction causes irreversible
kidney damage. Depending on the degree of obstruction,
pressure builds up, beginning at the site of obstruction and
moving backward from the ureter or renal pelvis into the
calices and collecting tubules. Typically, the most severe effects occur at the level of the papillae because these structures are subjected to the greatest pressure. Damage to the
nephrons and other functional components of the kidney
is caused by compression from increased intrapelvic pressure and ischemia from disturbances in blood flow. Experiments have shown recovery of renal function after release
of complete obstruction of up to 4 weeks’ duration. Irreversible damage, however, can begin as early as 7 days.11
Dilatation of the ureters and renal pelves occurs with
prolonged urinary tract obstruction. When the obstruction
is in the distal ureter, the increased pressure dilates the
proximal ureter, a condition called hydroureter (Fig. 35-4).
Hydroureter also is a complication of bladder outflow obstruction due to prostatic hyperplasia (see Chapter 45).
With increasing pressure, the ureteral wall becomes severely
stretched and loses its ability to undergo peristaltic contractions. In extreme cases, the ureter may become so dilated that it resembles a loop of bowel. Hydronephrosis refers
to urine-filled dilatation of the renal pelvis and calices. The
degree of hydronephrosis depends on the duration, degree,
and site of obstruction. Bilateral hydronephrosis occurs
only when the obstruction is below the level of the ureters.
If the obstruction occurs at the level of the ureters or above,
hydronephrosis is unilateral. The kidney eventually is destroyed and appears as a thin-walled shell that is filled with
fluid (Fig. 35-5).
Manifestations
The manifestations of urinary obstruction depend on the
site of obstruction, the cause, and the rapidity with which
the condition developed. Most commonly, the person has
pain, signs and symptoms of UTI, and manifestations of
renal dysfunction, such as an impaired ability to concentrate urine. Changes in urine output may be misleading
because output may be normal or even high in cases of partial obstruction.
Pain, which often is the factor that causes a person to
seek medical attention, is the result of distention of the
bladder, collecting system, or renal capsule. Its severity is
related most closely to the rate rather than the degree of
distention. Pain most often occurs with acute obstruction,
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Renal Function
discomfort. When pain occurs, it is related to the site of
obstruction. Obstruction of the renal pelvis or upper ureter
causes pain and tenderness over the flank area. With lower
levels of obstruction, the pain may radiate to the testes in
the male or the labia in the female. With partial obstruction, particularly of the ureteropelvic junction, pain may
occur during periods of high fluid intake, when a high rate
of urine flow causes an acute distention of the renal pelvis.
Because of its visceral innervation, ureteral obstruction
may produce reflex impairment of gastrointestinal tract
peristalsis and motility with abdominal distention and, in
severe cases, paralytic ileus.
Hypertension is an occasional complication of urinary
tract obstruction. It is more common in cases of unilateral
obstruction in which renin secretion is enhanced, probably secondary to impaired renal blood flow. In these circumstances, removal of the obstruction often leads to a
reduction in blood pressure. When hypertension accompanies bilateral obstruction, renin levels usually are normal, and the elevated blood pressure probably is volume
related. The relief of bilateral obstruction leads to a loss of
volume and a decrease in blood pressure. In some cases, relieving the obstruction does not correct the hypertension.
Diagnosis and Treatment
FIGURE 35-4 Hydroureter caused by ureteral obstruction in a
woman with cancer of the uterus.
in which the distention of urinary structures is rapid. This
is in contrast to chronic obstruction, in which distention
is gradual and may not cause pain. Instead, gradual obstruction may produce only vague abdominal or back
Early diagnosis of urinary tract obstruction is important
because the condition usually is treatable and a delay in
therapy may result in permanent damage to the kidneys.
Diagnostic methods vary with the symptoms. Ultrasonography has proved to be the single most useful noninvasive
diagnostic modality for urinary obstruction. Radiologic
methods, CT scans, and intravenous urography may also
be used. Other diagnostic methods, such as urinalysis, are
used to determine the extent of renal involvement and
the presence of infection.
Treatment of urinary obstruction depends on the cause.
Urinary stone removal may be necessary, or surgical treatment of structural defects may be indicated.
RENAL CALCULI
FIGURE 35-5 Hydronephrosis. Bilateral urinary tract obstruction has
led to conspicuous dilatation of the ureters, pelves, and calices. The
kidney on the right shows severe cortical atrophy. (Rubin E., Farber
J.L. [1999]. Pathology [3rd ed., p. 910]. Philadelphia: Lippincott-Raven)
The term nephrolithiasis refers to kidney stones. The most
common cause of upper urinary tract obstruction is urinary
calculi. Although stones can form in any part of the urinary
tract, most develop in the kidneys. Urinary stones are the
third most common disorder of the urinary tract, exceeded
only by UTIs and prostate disorders.12 Men are two to three
times more likely to develop stones than women.13
Kidney stones are crystalline structures made up of
materials that the kidneys normally excrete in the urine.
The etiology of urinary stone formation is complex, and
not all aspects are well understood. It is thought to encompass a number of factors, including increases in blood
and urinary levels of stone components and interactions
among the components; anatomic changes in urinary tract
structures; metabolic and endocrine influences; dietary
and intestinal absorption factors; and UTI. To add to the
mystery of stone formation is the fact that although both
kidneys are exposed to the same urinary constituents, kid-
CHAPTER 35
KIDNEY STONES
➤ Kidney stones are crystalline structures that form from
components of the urine.
➤ Stones require a nidus to form and a urinary environment
that supports continued crystallization of stone components.
➤ The development of kidney stones is influenced by the
concentration of stone components in the urine, the ability
of the stone components to complex and form stones, and
the presence of substances that inhibit stone formation.
ney stones tend to form in only one kidney. Three major
theories are used to explain stone formation: the saturation theory, the matrix theory, and the inhibitor deficiency theory.14–17 One or more of these theories may apply
to stone formation in the same person.
Kidney stones require a nidus, or nucleus, to form
and a urinary environment that supports continued precipitation of stone components to grow. The saturation
theory states that the risk for stone formation is increased
when the urine is supersaturated with stone components
(e.g., calcium salts, uric acid, magnesium ammonium phosphate, cystine). Supersaturation depends on urinary pH,
solute concentration, ionic strength, and complexation.
The greater the concentration of two ions, the more likely
they are to precipitate. Complexation influences the availability of specific ions. For example, sodium complexes
with oxalate and decreases its free ionic form.
The matrix theory proposes that organic materials, such
as mucopolysaccharides derived from the epithelial cells
that line the tubules, act as a nidus for stone formation.
TABLE 35-2
Disorders of Renal Function
This theory is based on the observation that organic matrix
materials can be found in all layers of kidney stones. It is
not known whether the matrix material contributes to the
initiation of stone formation or the material is merely entrapped as the stone forms.
Proteins produced by the kidney inhibit all phases of
crystallization. The inhibitor theory suggests that persons
who have a deficiency of proteins that inhibit stone formation in their urine are at increased risk for stone formation.
Kidney cells produce at least three proteins that are thought
to slow the rate of calcium oxalate crystallization: nephrocalcin, Tamm-Horsfall mucoprotein, and uropontin.14,15,18
Nephrocalcin inhibits nucleation, aggregation, and growth
of calcium oxalate stones. Tamm-Horsfall mucoprotein is
thought to exert a minor effect on crystal aggregation. Uropontin inhibits the growth of calcium oxalate crystals.
Much of the information about the function of organic inhibitors in terms of stone formation is still experimental.
Nonorganic substances also can act as inhibitors of stone
formation. For example, citrate is a key factor affecting development of calcium stones. It complexes with calcium,
thereby decreasing the concentration of ionic calcium. Citrate is a normal byproduct of the citric acid cycle in renal
cells; metabolic stimuli that consume this product (as with
metabolic acidosis due to fasting or hypokalemia) reduce
the urinary concentration of citrate. Citrate supplementation (potassium citrate) may be used in the treatment of
some forms of hypocitraturic kidney stones.12
Types of Stones
There are four basic types of kidney stones: calcium stones
(i.e., oxalate or phosphate), magnesium ammonium phosphate stones, uric acid stones, and cystine stones. The
causes and treatment measures for each of these types of
renal stones are described in Table 35-2.
Composition, Contributing Factors, and Treatment of Kidney Stones
Type of Stone
Contributing Factors
Treatment
Calcium (oxalate and phosphate)
Hypercalcemia and hypercalciuria
Immobilization
Treatment of underlying conditions
Increased fluid intake
Thiazide diuretics
Hyperparathyroidism
Vitamin D intoxication
Diffuse bone disease
Milk-alkali syndrome
Renal tubular acidosis
Hyperoxaluria
Magnesium ammonium
phosphate (struvite)
Urinary tract infections
Uric acid (urate)
Formed in acid urine with pH of
approximately 5.5
Gout
High-purine diet
Cystinuria (inherited disorder of
amino acid metabolism)
Cystine
815
Dietary restriction of foods high in oxalate
Treatment of urinary tract infection
Acidification of the urine
Increased fluid intake
Increased fluid intake
Allopurinol for hyperuricuria
Alkalinization of urine
Increased fluid intake
Alkalinization of urine
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Renal Function
Most kidney stones (70% to 80%) are calcium stones—
calcium oxalate, calcium phosphate, or a combination of
the two materials. Calcium stones usually are associated
with increased concentrations of calcium in the blood and
urine. Excessive bone resorption caused by immobility,
bone disease, hyperparathyroidism, and renal tubular acidosis all are contributing conditions. High oxalate concentrations in the blood and urine predispose to formation of
calcium oxalate stones.
Magnesium ammonium phosphate stones, also called
struvite stones, form only in alkaline urine and in the presence of bacteria that possess an enzyme called urease, which
splits the urea in the urine into ammonia and carbon dioxide. The ammonia that is formed takes up a hydrogen ion to
become an ammonium ion, increasing the pH of the urine
so that it becomes more alkaline. Because phosphate levels
are increased in alkaline urine and because magnesium
always is present in the urine, struvite stones form. These
stones enlarge as the bacterial count grows, and they can increase in size until they fill an entire renal pelvis (Fig. 35-6).
Because of their shape, they often are called staghorn stones.
Staghorn stones almost always are associated with UTIs and
persistently alkaline urine. Because these stones act as a foreign body, treatment of the infection often is difficult. Struvite stones usually are too large to be passed and require
lithotripsy or surgical removal.
Uric acid stones develop in conditions of gout and high
concentrations of uric acid in the urine. Hyperuricosuria
also may contribute to calcium stone formation by acting as
a nucleus for calcium oxalate stone formation. Unlike radiopaque calcium stones, uric acid stones are not visible on
x-ray films. Uric acid stones form most readily in urine with
a pH of 5.1 to 5.9.14 Thus, these stones can be treated by raising the urinary pH to 6 to 6.5 with potassium alkali salts.
Cystine stones are rare. They are seen in cystinuria,
which results from a genetic defect in renal transport of
cystine. These stones resemble struvite stones except that
infection is unlikely to be present.
Manifestations
One of the major manifestations of kidney stones is pain.
Depending on location, there are two types of pain associated with kidney stones: renal colic and noncolicky renal
pain.12,13 Renal colic is the term used to describe the colicky
pain that accompanies stretching of the collecting system
or ureter. The symptoms of renal colic are caused by stones
1 to 5 mm in diameter that can move into the ureter and
obstruct flow. Classic ureteral colic is manifested by acute,
intermittent, and excruciating pain in the flank and upper
outer quadrant of the abdomen on the affected side. The
pain may radiate to the lower abdominal quadrant, bladder area, perineum, or scrotum in the male. The skin may
be cool and clammy, and nausea and vomiting are common. Noncolicky pain is caused by stones that produce
distention of the renal calices or renal pelvis. The pain usually is a dull, deep ache in flank or back that can vary in intensity from mild to severe. The pain is often exaggerated
by drinking large amounts of fluid.
Diagnosis and Treatment
FIGURE 35-6 Staghorn calculi. The kidney shows hydronephrosis
and stones that are casts of the dilated calices. (Rubin E., Farber J.L.
[1999]. Pathology [3rd ed., p. 909]. Philadelphia: Lippincott-Raven)
Patients with kidney stones often present with acute renal
colic, and the diagnosis is based on symptomatology and
diagnostic tests, which include urinalysis, plain film radiography, intravenous pyelography, and abdominal ultrasonography.13 Urinalysis provides information related to
hematuria, infection, the presence of stone-forming crystals, and urine pH. At least 90% of stones are radiopaque
and readily visible on a plain radiograph of the abdomen.
Intravenous pyelography uses an intravenously injected
contrast medium that is filtered in the glomeruli to visualize the collecting system and the ureters of the kidneys.
Abdominal ultrasound is highly sensitive to hydronephrosis, which may be a manifestation of ureteral obstruction.
Retrograde urography and CT scanning also may be used.
A new imaging technique called nuclear scintigraphy uses
bisphosphonate markers as a means of imaging stones.12
The method has been credited with identifying stones that
are too small to be detected by other methods.
Treatment of acute renal colic usually is supportive.
Pain relief may be needed during acute phases of obstruction, and antibiotic therapy may be necessary to treat urinary infections. Most stones that are less than 5 mm in
diameter pass spontaneously. All urine should be strained
during an attack in the hope of retrieving the stone for
chemical analysis and determination of type. This information, along with a careful history and laboratory tests,
provides the basis for long-term preventive measures.
A major goal of treatment in persons who have passed
kidney stones or have had them removed is to prevent
CHAPTER 35
their recurrence. Prevention requires investigation into the
cause of stone formation using urine tests, blood chemistries, and stone analysis. Underlying disease conditions,
such as hyperparathyroidism, are treated. Adequate fluid
intake reduces the concentration of stone-forming crystals
in the urine and needs to be encouraged. Depending on
the type of stone that is formed, dietary changes, medications, or both may be used to alter the concentration of
stone-forming elements in the urine. For example, persons
who form calcium oxalate stones may need to decrease
their intake of foods that are high in oxalate (e.g., spinach,
Swiss chard, cocoa, chocolate, pecans, peanuts). Calcium
supplementation with calcium salts such as calcium carbonate and calcium phosphate also may be used to bind oxalate in the intestine and decrease its absorption. Thiazide
diuretics lower urinary calcium by increasing tubular reabsorption so that less remains in the urine. Drugs that
bind calcium in the gut (e.g., cellulose phosphate) may be
used to inhibit calcium absorption and urinary excretion.
Measures to change the pH of the urine also can influence kidney stone formation. In persons who lose the
ability to lower the pH of (or acidify) their urine, there is
an increase in the divalent and trivalent forms of urine
phosphate that combine with calcium to form calcium
phosphate stones. The formation of uric acid stones is increased in acid urine; stone formation can be reduced by
raising the pH of urine to 6.0 to 6.5 with potassium alkali
(e.g., potassium citrate) salts. Table 35-2 summarizes measures for preventing the recurrence of different types of
kidney stones.
In some cases, stone removal may be necessary. Several methods are available for removing kidney stones:
ureteroscopic removal, percutaneous removal, and extracorporeal lithotripsy. All these procedures eliminate the
need for an open surgical procedure, which is another form
of treatment. Open stone surgery may be required to remove large calculi or those that are resistant to other forms
of removal.
Ureteroscopic removal involves the passage of an instrument through the urethra into the bladder and then
into the ureter. The development of high-quality optics has
improved the ease with which this procedure is performed
and its outcome. The procedure, which is performed under
fluoroscopic guidance, involves the use of various instruments for dilating the ureter and for grasping, fragmenting,
and removing the stone. Preprocedure radiologic studies
using a contrast medium (i.e., excretory urography) are
done to determine the position of the stone and direct the
placement of the ureteroscope.
Percutaneous nephrolithotomy is the treatment of
choice for removal of renal or proximal ureteral calculi.
It involves the insertion through the flank of a smallgauge needle into the collecting system of the kidney; the
needle tract is then dilated, and an instrument called a
nephroscope is inserted into the renal pelvis. The procedure
is performed under fluoroscopic guidance. Preprocedure
radiologic and ultrasonographic examinations of the kidney and ureter are used in determining the placement of
the nephroscope. Stones up to 1 cm in diameter can be removed through this method. Larger stones must be bro-
Disorders of Renal Function
817
ken up with an electrohydraulic or ultrasonic lithotriptor
(i.e., stone breaker).
A nonsurgical treatment called extracorporeal shockwave lithotripsy, introduced in Germany in 1980, received
U.S. Food and Drug Administration approval in 1984 for
treatment of stones primarily in the renal calyx and pelvis
and the upper third of the ureter. The procedure uses
acoustic shock waves to fragment calculi into sandlike particles that are passed in the urine over the next few days.
Because of the large amount of stone particles that are generated during the procedure, a ureteral stent (i.e., tubelike
device used to hold the ureter open) may be inserted to
ensure adequate urine drainage.
In summary, obstruction of urine flow can occur at any level
of the urinary tract. Among the causes of urinary tract obstruction are developmental defects, pregnancy, infection and
inflammation, kidney stones, neurologic defects, and prostatic
hypertrophy. Obstructive disorders produce stasis of urine, increasing the risk for infection and calculi formation and resulting in backpressure that is damaging to kidney structures.
Kidney stones are a major cause of upper urinary tract
obstruction. There are four types of kidney stones: calcium
(i.e., oxalate and phosphate) stones, which are associated with
increased serum calcium levels; magnesium ammonium phosphate (i.e., struvite) stones, which are associated with UTIs; uric
acid stones, which are related to elevated uric acid levels; and
cystine stones, which are seen in cystinuria. A major goal of
treatment for persons who have passed kidney stones or have
had them removed is to identify stone composition and prevent their recurrence. Treatment measures depend on stone
type and include adequate fluid intake to prevent urine saturation, dietary modification to decrease intake of stone-forming
constituents, treatment of UTI, measures to change urine pH,
and the use of diuretics that decrease the calcium concentration of urine.
Urinary Tract Infections
After completing this section of the chapter, you should be able to
meet the following objectives:
✦ Cite the organisms most responsible for UTIs and state
✦
✦
✦
✦
✦
why urinary catheters, obstruction, and reflux predispose
to infections
List three physiologic mechanisms that protect against UTIs
Compare the signs and symptoms of upper and lower UTIs
Describe factors that predispose to UTIs in children,
sexually active women, pregnant women, and older
adults
Compare the manifestations of UTIs in different age
groups, including infants, toddlers, adolescents, adults,
and older adults
Cite measures used in the diagnosis and treatment of UTIs
Urinary tract infections are the second most common
type of bacterial infections seen by health care providers, res-
818
UNIT VIII
Renal Function
piratory tract infections being the first. Each year, more than
8 million people are diagnosed with UTIs. According to the
1997 National Ambulatory Medical Care Survey, UTI accounted for nearly 7 million office visits and 1 million emergency room visits, resulting in 100,000 hospitalizations.19
ETIOLOGIC FACTORS
UTIs can include several distinct entities, including asymptomatic bacteriuria, symptomatic infections, lower UTIs
such as cystitis, and upper UTIs such as pyelonephritis. Because of their ability to cause renal damage, upper UTIs are
considered more serious than lower UTIs.
Most uncomplicated UTIs are caused by Escherichia coli.
Other uropathic pathogens include Staphylococcus saprophyticus in uncomplicated UTIs, and both non–E. coli gramnegative rods (Proteus mirabilis, Klebsiella pneumoniae, and
Enterobacter, Pseudomonas, and Serratia species) and grampositive cocci (Staphylococcus aureus, group B streptococci)
in complicated UTIs.20–22 Most UTIs are caused by bacteria
that enter through the urethra. Bacteria can also enter
through the bloodstream, usually in immunocompromised
persons and neonates. Although the distal portion of the
urethra often contains pathogens, the urine formed in the
kidneys and found in the bladder normally is sterile or free
of bacteria. This is because of the washout phenomenon, in
which urine from the bladder normally washes bacteria out
of the urethra. When a UTI occurs, it is usually from bacteria that have colonized the urethra, vagina, or perianal area.
There is an increased risk for UTI in persons with urinary obstruction and reflux; in people with neurogenic
disorders that impair bladder emptying; in women who
are sexually active, especially if they use a diaphragm or
spermicide for contraception; in postmenopausal women;
in men with diseases of the prostate; and in elderly persons. Instrumentation and urinary catheterization are the
most common predisposing factors for nosocomial UTIs.
UTIs occur more commonly in women with diabetes than
in women without the disease. People with diabetes are
also at increased risk for complications associated with
UTIs, including pyelonephritis, and they are more susceptible to fungal infections (particularly, Candida species) and
infections with gram-negative pathogens other than E. coli,
both of which are accompanied by increased severity and
unusual manifestations.23
URINARY TRACT INFECTIONS
➤ Urinary tract infections involve both the lower and upper
urinary tract structures.
➤ In lower urinary tract infections, the infecting pathogens
tend to propagate in the urine and cause irritative voiding
symptoms, often with minimal systemic signs of infection.
➤ Upper urinary tract infections tend to invade the tissues of
the kidney pelvis, inciting an acute inflammatory response
with marked systemic manifestations of infection.
Host–Agent Interactions
Because certain people tend to be predisposed to development of UTIs, considerable interest has been focused on
host–pathogen interactions and factors that increase the
risk for UTI.
Host Defenses. In the development of a UTI, host defenses
are matched against the virulence of the pathogen. The
host defenses of the bladder have several components, including the washout phenomenon, in which bacteria are
removed from the bladder and urethra during voiding; the
protective mucin layer that lines the bladder and protects
against bacterial invasion; and local immune responses. In
the ureters, peristaltic movements facilitate the movement
of urine from the renal pelvis through the ureters and into
the bladder. Immune mechanisms, particularly secretory
immunoglobulin A (IgA), appear to provide an important
antibacterial defense. Phagocytic blood cells further assist
in the removal of bacteria from the urinary tract.
There has been a growing appreciation of the protective function of the bladder’s mucin layer.22 It is thought
that the epithelial cells that line the bladder synthesize
protective substances that subsequently become incorporated into the mucin layer that adheres to the bladder wall.
One theory proposes that the mucin layer acts by binding
water, which then constitutes a protective barrier between
the bacteria and the bladder epithelium. Elderly and postmenopausal women produce less mucin than younger
women, suggesting that estrogen may play a role in mucin
production in women.
Other important host factors include the normal flora
of the periurethral area in women and prostate secretions in
men. In women, the normal flora of the periurethral area,
which consists of organisms such as lactobacillus, provides
defense against the colonization of uropathic bacteria. Alterations in the periurethral environment, such as occurs
with a decrease in estrogen levels during menopause or the
use of antibiotics, can alter the protective periurethral flora,
allowing uropathogens to colonize and enter the urinary
tract. In men, the prostatic fluid has antimicrobial properties that protect the urethra from colonization.
Pathogen Virulence. Not all bacteria are capable of infecting the urinary tract. Of the many strains of E. coli and
other uropathogens, only those with adherence properties
are able to infect the urinary tract. These bacteria have fine
protein filaments that help them adhere to receptors on
the lining of urinary tract structures.22 These filaments are
called pili or fimbriae. Among the factors that contribute to
bacterial virulence, the type of pili that the bacteria possess
may be the most important. Bacteria with certain types of
pili are associated primarily with cystitis, and those with
other types are associated with a high incidence of pyelonephritis. The bacteria associated with pyelonephritis are
thought to have pili that bind to carbohydrates that are
specific to the surfaces of epithelial cells in this part of the
urinary tract.
Obstruction and Reflux
Obstruction and reflux are important contributing factors
in the development of UTIs. Any microorganisms that
CHAPTER 35
enter the bladder normally are washed out during voiding.
When outflow is obstructed, urine remains in the bladder
and acts as a medium for microbial growth; the microorganisms in the contaminated urine can then ascend along
the ureters to infect the kidneys. The presence of residual
urine correlates closely with bacteriuria and with its recurrence after treatment. Another aspect of bladder outflow
obstruction and bladder distention is increased intravesicular pressure, which compresses blood vessels in the bladder wall, leading to a decrease in the mucosal defenses of
the bladder.
In UTIs associated with stasis of urine flow, the obstruction may be anatomic or functional. Anatomic obstructions include urinary tract stones, prostatic hyperplasia,
pregnancy, and malformations of the ureterovesical junction. Functional obstructions include neurogenic bladder,
infrequent voiding, detrusor (bladder) muscle instability,
and constipation.
Reflux occurs when urine from the urethra moves into
the bladder (i.e., urethrovesical reflux) or from the bladder
into the ureters (i.e., vesicoureteral reflux). In women, urethrovesical reflux can occur during activities such as coughing or squatting, in which an increase in intra-abdominal
pressure causes the urine to be squeezed into the urethra
and then to flow back into the bladder as the pressure decreases. This also can happen when voiding is abruptly
interrupted. Because the urethral orifice frequently is contaminated with bacteria, the reflux mechanism may cause
bacteria to be drawn back into the bladder.
A second type of reflux mechanism, vesicoureteral reflux, occurs at the level of the bladder and ureter. Normally,
the distal portion of the ureter courses between the muscle layer and the mucosal surface of the bladder wall, forming a flap. The flap is compressed against the bladder wall
during micturition, preventing urine from being forced
into the ureter (Fig. 35-7). In persons with vesicoureteral
reflux, the ureter enters the bladder at an approximate
right angle such that urine is forced into the ureter during
micturition. It is seen most commonly in children with
UTIs and is believed to result from congenital defects in
length, diameter, muscle structure, or innervation of the
submucosal segment of the ureter. Vesicoureteral reflux
also is seen in adults with obstruction to bladder outflow,
primarily due to increased bladder volume and pressure.
Disorders of Renal Function
819
FIGURE 35-7 Anatomic features of the bladder and kidney in pyelonephritis caused by vesicoureteral reflux. Bladder. (A) In the normal
bladder, the distal portion of the intravesical ureter courses between
the mucosa and the muscularis of the bladder. A mucosal flap is thus
formed. On micturition, the elevated intravesicular pressure compresses the flap against the bladder wall, thereby occluding the
lumen. (B) Persons with a congenitally short intravesical ureter have
no mucosal flap, because the entry of the ureter into the bladder approaches a right angle. Thus, micturition forces urine into the ureter.
(Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 903]. Philadelphia:
Lippincott-Raven) (Courtesy of Dmitri Karetnikov, artist)
Catheter-Induced Infection
Urinary catheters are tubes made of latex or plastic. They
are inserted through the urethra into the bladder for the
purpose of draining urine. They are a source of urethral
irritation and provide a means for entry of microorganisms into the urinary tract.
Catheter-associated bacteriuria remains the most frequent cause of gram-negative septicemia in hospitalized
patients. Studies have shown that bacteria adhere to the
surface of the catheter and initiate the growth of a biofilm
that then covers the surface of the catheter.24 The biofilm
tends to protect the bacteria from the action of antibiotics
and makes treatment difficult. A closed drainage system
(i.e., closed to air and other sources of contamination) and
careful attention to perineal hygiene (i.e., cleaning the area
around the urethral meatus) help to prevent infections in
persons who require an indwelling catheter. Careful hand
washing and early detection and treatment of UTIs also are
essential.
MANIFESTATIONS
The manifestations of UTI depend on whether the infection
involves the lower (bladder) or upper (kidney) urinary tract
and whether the infection is acute or chronic. Most UTIs
are acute uncomplicated bladder infections that occur in
women. Upper UTIs are less common and occur more frequently in children and adults with urinary tract obstructions or other predisposing conditions such as diabetes.
820
UNIT VIII
Renal Function
An acute episode of cystitis (bladder infection) is characterized by frequency of urination (sometimes as often as
every 20 minutes), lower abdominal or back discomfort,
and burning and pain on urination (i.e., dysuria). Occasionally, the urine is cloudy and foul smelling. In adults,
fever and other signs of infection usually are absent. If
there are no complications, the symptoms disappear within
48 hours of treatment. The symptoms of cystitis also may
represent urethritis caused by Chlamydia trachomatis, Neisseria gonorrhoeae, or herpes simplex virus, or vaginitis attributable to Trichomonas vaginalis or Candida species (see
Chapter 48).
Upper UTIs affect the parenchyma and pelvis of the
kidney (pyelonephritis). They tend to produce more systemic signs of infection than lower UTIs because of closer
proximity to the vascular compartment and blood cells
(e.g., neutrophils) that incite the inflammatory response.
Acute pyelonephritis tends to present with an abrupt onset of shaking chills, moderate to high fever, and constant
ache in the loin area of the back that is unilateral or bilateral.22 Lower urinary tract symptoms, including dysuria,
frequency, and urgency, also are common. There may be
significant malaise, and the person usually looks and feels
ill. Nausea and vomiting may occur along with abdominal
pain. Palpation or percussion over the costovertebral angle
on the affected side usually causes pain. Chronic pyelonephritis, which results from repeated kidney infections
that cause scarring and atrophy of the kidney, often is
asymptomatic, and the condition is detected during evaluation for complications associated with renal insufficiency, such as hypertension.
DIAGNOSIS AND TREATMENT
Diagnosis
The diagnosis of UTI usually is based on symptoms and on
examination of the urine for the presence of microorganisms. When necessary, x-ray films, ultrasonography, and
CT and renal scans are used to identify contributing factors, such as obstruction.
Microscopic urine tests are used to establish the presence of bacteria and blood cells in the urine.22 A commonly accepted criterion for diagnosis of a UTI is the
presence of 105 or more bacteria per milliliter of urine.22
Colonization usually is defined as the multiplication of
microorganisms in or on a host without apparent evidence
of invasiveness or tissue injury. Pyuria (the presence of less
than five to eight leukocytes per high-power field) indicates a host response to infection rather than asymptomatic bacterial colonization. A Gram stain may be done to
determine the type of organism that is present (gram positive or gram negative).
Chemical screening (urine dipstick) for markers of infection may provide useful information but is less sensitive
than microscopic analysis. Bacteria reduce nitrates in the
urine to nitrites, providing a means for chemical analysis.
Similarly, activated leukocytes secrete leukocyte esterase,
which can be detected chemically. These two chemical
tests have sensitivities ranging from 80% and rarely are
positive in the absence of infection.11 Therefore, they are
commonly used as a screening tool in persons with symptoms of UTI. The tests are relatively inexpensive, easy to
perform, and can be done in the clinic setting or even in
the home. A urine culture confirms the presence of pathogenic bacteria in urine specimens, allows for their identification, and permits the determination of their sensitivity
to specific antibiotics.
Treatment
The treatment of UTI is based on the type of infection that
is present (lower or upper UTI), the pathogen causing the
infection, and the presence of contributing host–agent factors. Other considerations include whether the infection
is acute, recurrent, or chronic.
Acute Urinary Tract Infections. Most acute lower UTIs,
which occur mainly in women and are generally caused by
E. coli, are treated successfully with a short course of antimicrobial therapy. Forcing fluids may relieve signs and
symptoms, and this approach is used as an adjunct to antimicrobial treatment. For several decades, first-line therapy
for acute uncomplicated UTI has been a 3-day regimen of
trimethoprim-sulfamethoxazole (TMP-SMX).25 However,
there is increasing resistance among commonly acquired
E. coli infections to TMP-SMX in many parts of the United
States, varying from 22% to 39% depending on geographic
location.26 The resistance of E. coli to TMP-SMX is often accompanied by resistance to other antimicrobial drugs, including ampicillin, cephalothin, and tetracycline. Thus,
selection of a therapeutic agent must now take into account the geographic location and susceptibility of the
bacteria to the different antimicrobial agents.
Because there is risk for permanent kidney damage
with pyelonephritis, these infections are treated more aggressively. Treatment with an appropriate antimicrobial
agent usually is continued for 10 to 14 days. Hospitalization may be recommended during the early stages of infection until a response to treatment is observed.27
Recurrent Urinary Tract Infections. Recurrent lower UTIs
are those that recur after treatment. They are due either to
bacterial persistence or reinfection. Bacterial persistence
usually is curable by removal of the infectious source
(e.g., urinary catheter or infected bladder stones). Reinfection is managed principally through education regarding
pathogen transmission and prevention measures. Cranberry juice or blueberry juice has been suggested as a preventive measure for persons with frequent UTIs. Studies
suggest that these juices reduce bacterial adherence to the
epithelial lining of the urinary tract.28,29 Because of their
mechanism of action, these juices are used more appropriately in prevention rather than treatment of an established UTI.
Chronic Urinary Tract Infections. Chronic UTIs are more
difficult to treat. Because they often are associated with obstructive uropathy or reflux flow of urine, diagnostic tests
usually are performed to detect such abnormalities. When
possible, the condition causing the reflux flow or obstruction is corrected. Most persons with recurrent UTIs are
treated with antimicrobial agents for 10 to 14 days in doses
sufficient to maintain high urine levels of the drug, and
CHAPTER 35
they are examined for obstruction or other causes of infection. Men in particular should be investigated for obstructive disorders or a prostatic focus of infection.
INFECTIONS IN SPECIAL POPULATIONS
Urinary tract infections affect persons of all ages. In infants, they occur more often in boys than in girls. After the
first year of life, however, UTIs are more frequent in females because of the shorter length of the urethra and because the vaginal vestibule can be easily contaminated
with fecal flora. Approximately half of all adult women
have at least one UTI during their lifetime.30 In men, the
longer length of the urethra and the antibacterial properties of the prostatic fluid provide some protection from ascending UTIs until approximately 50 years of age. After
this age, prostatic hypertrophy becomes more common,
and with it may come obstruction and increased risk for
UTI (see Chapter 45).
Disorders of Renal Function
821
pregnancy, and premature delivery. Evidence suggests that
few women become bacteriuric during pregnancy. Rather,
it appears that symptomatic UTIs during pregnancy reflect
preexisting asymptomatic bacteriuria and that changes
occurring during pregnancy simply permit the prior urinary colonization to lead to symptomatic infection and
invasion of the kidneys.33 Untreated asymptomatic bacteriuria leads to symptomatic cystitis in approximately 30%
of pregnant women.33 Because bacteriuria may occur as an
asymptomatic condition in pregnant women, the American
College of Obstetrics and Gynecology recommends that a
urine culture be obtained at the first prenatal visit.34 A repeat culture should be obtained during the third trimester.
Women with bacteriuria should be followed closely, and
infections should be properly treated to prevent complications. The choice of antimicrobial agent should address
the common infecting organisms and should be safe for
the mother and fetus.
Urinary Tract Infections in Children
Urinary Tract Infections in Women
In women, the urethra is short and close to the vagina and
rectum, offering little protection against entry of microorganisms into the bladder. There is a peak incidence of
these infections in the 15- to 24-year-old age group, suggesting that hormonal and anatomic changes associated
with puberty and sexual activity contribute to UTIs.
The role of sexual activity in the development of urethritis and cystitis is controversial. The well-documented
“honeymoon cystitis” suggests that sexual activity may
contribute to such infections in susceptible women. The
anterior urethra usually is colonized with bacteria; urethral
massage or sexual intercourse can force these bacteria back
into the bladder. Using a diaphragm and spermicide enhances the susceptibility to infection.30,31 A nonpharmacologic approach to the treatment of frequent UTIs associated
with sexual intercourse is to increase fluid intake before intercourse and to void soon after intercourse. This procedure
uses the washout phenomenon to remove bacteria from
the bladder.
Pregnant women are at increased risk for UTIs. Normal
changes in the functioning of the urinary tract that occur
during pregnancy predispose to UTIs.32 These changes involve the collecting system of the kidneys and include dilatation of the renal calices, pelves, and ureters that begins
during the first trimester and becomes most pronounced
during the third trimester. This dilatation of the upper
urinary system is accompanied by a reduction in the peristaltic activity of the ureters that is thought to result from
the muscle-relaxing effects of progesterone-like hormones
and mechanical obstruction from the enlarging uterus. In
addition to the changes in the kidneys and ureters, the
bladder becomes displaced from its pelvic position to a
more abdominal position, producing further changes in
ureteral position.
Asymptomatic UTIs are common, with a prevalence
rate of 10% in pregnant women. The complications of
asymptomatic UTIs during pregnancy include persistent
bacteriuria, acute and chronic pyelonephritis, toxemia of
Urinary tract infections occur in as many as 3% to 5% of
female and 1% of male children.4,35 In girls, the average age
at first diagnosis is 5 years or younger, with peaks during
infancy and toilet training. In boys, most UTIs occur during the first year of life; they are more common in uncircumcised than in circumcised boys. Children who are at
increased risk for bacteriuria or symptomatic UTIs are premature infants discharged from neonatal intensive care
units; children with systemic or immunologic disease or
urinary tract abnormalities such as neurogenic bladder
or vesicoureteral reflux; those with a family history of UTI
or urinary tract anomalies with reflux; and girls younger
than 5 years of age with a history of UTI.4,35
UTIs in children frequently involve the upper urinary
tract (pyelonephritis). In children in whom renal development is not complete, pyelonephritis can lead to renal scarring and permanent kidney damage. It has been reported
that more than 75% of children younger than 5 years of
age with febrile UTIs have pyelonephritis, and that renal
scarring occurs in 27% to 64% of children with pyelonephritis.36 Most UTIs that lead to scarring and diminished
kidney growth occur in children younger than 4 years, especially infants younger than 1 year of age. The incidence
of scarring is greatest in children with gross vesicoureteral
reflux or obstruction, in children with recurrent UTIs, and
in those with a delay in treatment.
Unlike adults, children frequently do not present with
the typical signs of a UTI.36,37 Many neonates with UTIs
have bacteremia and may show signs and symptoms of
septicemia, including fever, hypothermia, apneic spells,
poor skin perfusion, abdominal distention, diarrhea, vomiting, lethargy, and irritability. Older infants may present
with feeding problems, failure to thrive, diarrhea, vomiting, fever, and foul-smelling urine. Toddlers often present
with abdominal pain, vomiting, diarrhea, abnormal voiding patterns, foul-smelling urine, fever, and poor growth.
In older children with lower UTIs, the classic features—
enuresis, frequency, dysuria, and suprapubic discomfort—
are more common. Fever is a common sign of UTI in
822
UNIT VIII
Renal Function
children, and the possibility of UTI should be considered
in children with unexplained fever.
Diagnosis is based on a careful history of voiding
patterns and symptomatology; physical examination to
determine fever, hypertension, abdominal or suprapubic
tenderness, and other manifestations of UTI; and urinalysis to determine bacteriuria, pyuria, proteinuria, and hematuria. A positive urine culture that is obtained correctly is
essential for the diagnosis. Additional diagnostic methods
may be needed to determine the cause of the disorder.
Vesicoureteral reflux is the most commonly associated abnormality in UTIs, and reflux nephropathy is an important cause of end-stage renal disease in children and
adolescents. Children with a relatively uncomplicated first
UTI may turn out to have significant reflux. Therefore,
even a single documented UTI in a child requires careful
diagnosis. Urinary symptoms in the absence of bacteriuria
suggest vaginitis, urethritis, sexual molestation, the use of
irritating bubble baths, pinworms, or viral cystitis. In adolescent girls, a history of dysuria and vaginal discharge
makes vaginitis or vulvitis a consideration.
The approach to treatment is based on the clinical
severity of the infection, the site of infection (i.e., lower
versus upper urinary tract), the risk for sepsis, and the presence of structural abnormalities. The immediate treatment
of infants and young children is essential. Most infants
with symptomatic UTIs and many children with clinical
evidence of acute upper UTIs require hospitalization and
intravenous antibiotic therapy. Follow-up is essential for
children with febrile UTIs to ensure resolution of the infection. Follow-up urine cultures often are done at the end
of treatment. Imaging studies often are recommended for
all children after first UTIs to detect renal scarring, vesicoureteral reflux, or other abnormalities.36,38
Urinary Tract Infections in the Elderly
Urinary tract infections are relatively common in elderly
persons.35 They are the second most common form of infection, after respiratory tract infections, among otherwise
healthy community-dwelling elderly. It is particularly prevalent in elderly living in nursing homes or extended-care
facilities.
Most of these infections follow invasion of the urinary
tract by the ascending route. Several factors predispose
elderly persons to UTIs: immobility resulting in poor bladder emptying, bladder outflow obstruction caused by prostatic hyperplasia or kidney stones, bladder ischemia caused
by urine retention, senile vaginitis, constipation, and diminished bactericidal activity of urine and prostatic secretions. Added to these risks are other health problems that
necessitate instrumentation of the urinary tract. UTIs develop in 1% of ambulatory patients after a single catheterization and within 3 to 4 days in essentially all patients
with indwelling catheters.39
Elderly persons with bacteriuria have varying symptoms, ranging from the absence of symptoms to the presence of typical UTI symptoms. Even when symptoms of
lower UTIs are present, they may be difficult to interpret
because elderly persons without UTIs commonly experi-
ence urgency, frequency, and incontinence. Alternatively,
elderly persons may have vague symptoms such as anorexia, fatigue, weakness, or change in mental status. Even
with more serious upper UTIs (e.g., pyelonephritis), the
classic signs of infection such as fever, chills, flank pain,
and tenderness may be altered or absent in elderly persons.35 Sometimes, no symptoms occur until the infection
is far advanced.
In summary, UTI is the second most common type of bacterial infection seen by health care professionals. Infections can
range from simple bacteriuria to severe kidney infections that
cause irreversible kidney damage. Predisposition to infection
is determined by host defenses and pathogen virulence. Host
defenses include the washout phenomenon associated with
voiding, the protective mucin lining of the bladder, and the
local immune defenses. Pathogen virulence is enhanced by
the presence of pili that facilitate adherence to structures in the
urinary tract.
Most UTIs ascend from the urethra and bladder. A number
of factors interact in determining the predisposition to development of UTIs, including urinary tract obstruction, urine stasis and reflux, pregnancy-induced changes in urinary tract
function, age-related changes in the urinary tract, changes in
the protective mechanisms of the bladder and ureters, impaired immune function, and virulence of the pathogen. Urinary tract catheters and urinary instrumentation contribute to
the incidence of UTIs. Early diagnosis and treatment of UTI are
essential to preventing permanent kidney damage.
Disorders of Glomerular Function
After completing this section of the chapter, you should be able to
meet the following objectives:
✦ Describe the two types of immune mechanisms involved
in glomerular disorders
✦ Use the terms proliferation, sclerosis, membranous, diffuse,
focal, segmental, and mesangial to explain changes in
glomerular structure that occur with glomerulonephritis
✦ Relate the proteinuria, hematuria, pyuria, oliguria,
edema, hypertension, and azotemia that occur with
glomerulonephritis to changes in glomerular structure
✦ Differentiate the pathology and manifestations of the
nephrotic syndrome from those of the nephritic
syndrome
The glomeruli are tufts of capillaries that lie between
the afferent and efferent arterioles. The capillaries of the
glomeruli are arranged in lobules and supported by a stalk
consisting of mesangial cells and a basement membrane–
like extracellular matrix (Fig. 35-8). The glomerular capillary membrane is composed of three structural layers that
constitute its permeability characteristics: an endothelial
cell layer lining the capillary, a basement membrane made
up of a network of matrix proteins, and a layer of epithelial
cells forming the outer surface of the capillary and lining
CHAPTER 35
A
B
FIGURE 35-8 Schematic representation of glomerulus. (A) Normal;
(B) localization of immune deposits (mesangial, subendothelial,
subepithelial) and changes in glomerular architecture associated
with injury. (Whitley K., Keane W.F., & Vernier R.L. [1984]. Acute
glomerulonephritis: A clinical overview. Medical Clinics of North America 68 [2], 263)
Bowman’s capsule (see Chapter 32, Fig. 32-5). The epithelial cells are attached to the basement membrane by discrete
cytoplasmic extensions, the foot processes (i.e., podocytes).
In the glomeruli, blood is filtered, and the urine filtrate
formed. The capillary membrane is selectively permeable:
it allows water, electrolytes, and dissolved particles, such
as glucose and amino acids, to leave the capillary and enter
Bowman’s space and prevents larger particles, such as
plasma proteins and blood cells, from leaving the blood.
MECHANISMS OF GLOMERULAR INJURY
Glomerulonephritis, an inflammatory process that involves
glomerular structures, is the leading cause of chronic renal
failure in the United States, accounting for one half of persons with end-stage renal disease.40 There are many causes
of glomerular disease. The disease may occur as a primary
condition in which the glomerular abnormality is the only
disease present, or it may occur as a secondary condition
in which the glomerular abnormality results from another
disease, such as diabetes mellitus or SLE. An understand-
Disorders of Renal Function
823
ing of the various forms of glomerular disease has emerged
only recently. Much of this knowledge can be attributed
to advances in immunobiology and electron microscopy,
development of animal models, and increased use of renal
biopsy during the early stages of glomerular disease.
Glomerulonephritis is characterized by hematuria with
red cell casts, a diminished glomerular filtration rate (GFR),
azotemia (presence of nitrogenous wastes in the blood),
oliguria, and hypertension. It is caused by diseases that
provoke a proliferative inflammatory response of the endothelial, mesangial, or epithelial cells of the glomeruli. The
inflammatory process damages the capillary wall, permitting red blood cells to escape into the urine and producing
hemodynamic changes that decrease the GFR.
Although little is known about the causative agents or
triggering events that produce glomerular disease, most
cases of primary and many cases of secondary glomerular
disease probably have an immune origin.5,6,40–42 Two types
of immune mechanisms have been implicated in the development of glomerular disease: injury resulting from
antibodies reacting with fixed glomerular antigens, and injury resulting from circulating antigen–antibody complexes that become trapped in the glomerular membrane
(Fig. 35-9). Antigens responsible for development of the
immune response may be of endogenous origin, such as
auto-antibodies to DNA in SLE, or they may be of exogenous origin, such as streptococcal membrane antigens
in poststreptococcal glomerulonephritis. Frequently, the
source of the antigen is unknown.
SPECIFIC TYPES OF GLOMERULAR DISEASE
The cellular changes that occur with glomerular disease
include proliferative, sclerotic, and membranous changes.
The term proliferative refers to an increase in the cellular
components of the glomerulus, regardless of origin; sclerotic to an increase in the noncellular components of the
glomerulus, primarily collagen; and membranous to an increase in the thickness of the glomerular capillary wall,
often caused by immune complex deposition. Glomerular changes can be diffuse, involving all glomeruli and all
parts of the glomeruli; focal, in which only some glomeruli are affected and others are essentially normal; segmental, involving only a certain segment of each glomeruli;
or mesangial, affecting only the mesangial cell. Figure 35-8
shows changes associated with various types of glomerular disease.
Among the different types of glomerular diseases are
acute proliferative glomerulonephritis, rapidly progressive
glomerulonephritis, nephrotic syndrome, membranous glomerulonephritis, minimal change disease (lipoid nephrosis), focal segmental glomerulosclerosis, IgA nephropathy,
and chronic glomerulonephritis.
Acute Proliferative Glomerulonephritis
The most commonly recognized form of acute glomerulonephritis is diffuse proliferative glomerulonephritis, which
follows infections caused by strains of group A β-hemolytic
streptococci. Diffuse proliferative glomerulonephritis also
may occur after infections by other organisms, including
824
A
UNIT VIII
Renal Function
Antiglomerular
membrane antibodies
B
Circulating
antigen–antibody
complex deposition
Epithelial cell
Foot process
Basement
membrane
Subendothelial
deposit
Circulating
antigen–antibody
complexes
Antigen
Antibody
staphylococci and a number of viral agents, such as those
responsible for mumps, measles, and chickenpox. With this
type of glomerulonephritis, the inflammatory response is
caused by an immune reaction that occurs when circulating immune complexes become entrapped in the glomerular capillary membrane. Proliferation of the endothelial
cells lining the glomerular capillary (i.e., endocapillary form
of the disease) and the mesangial cells lying between the endothelium and the epithelium follows (see Fig. 35-8). The
capillary membrane swells and becomes permeable to
plasma proteins and blood cells. Although the disease is
seen primarily in children, adults of any age can be affected.
The classic case of poststreptococcal glomerulonephritis follows a streptococcal infection by approximately
7 to 12 days—the time needed for the development of
antibodies.40 Oliguria, which develops as the GFR decreases, is one of the first symptoms. Proteinuria and
hematuria follow because of increased glomerular capillary wall permeability. The red blood cells are degraded by
materials in the urine, and cola-colored urine may be the
first sign of the disorder. Sodium and water retention gives
rise to edema, particularly of the face and hands, and hypertension. Important laboratory findings include an elevated streptococcal exoenzyme (antistreptolysin O) titer,
a decline in C3 complement (see Chapter 19), and cryoglobulins (i.e., large immune complexes) in the serum.
Treatment of acute poststreptococcal glomerulonephritis is largely symptomatic. The acute symptoms usu-
GLOMERULAR DISORDERS
➤ Glomerular disorders affect the glomerular capillary structures that filter material from the blood.
➤ Nephritic syndromes are caused by diseases that produce
proliferative inflammatory responses that decrease the
permeability of the glomerular capillary membrane.
➤ The nephrotic syndrome is caused by disorders that increase the permeability of the glomerular capillary membrane, causing massive loss of protein in the urine.
FIGURE 35-9 Immune mechanisms
of glomerular disease. (A) Antiglomerular antibodies leave the circulation and interact with antigens
that are present in the basement
membrane of the glomerulus.
(B) Antigen–antibody complexes
circulating in the blood become
trapped as they are filtered in the
glomerulus.
ally begin to subside in approximately 10 days to 2 weeks,
although in some children, the proteinuria may persist for
several months. The immediate prognosis is favorable, and
approximately 95% of children recover spontaneously.5
The outlook for adults is less favorable; approximately
60% recover completely. In the remainder of cases, the lesions eventually resolve, but there may be permanent kidney damage.
Rapidly Progressive Glomerulonephritis
Rapidly progressive glomerulonephritis is a clinical syndrome characterized by signs of severe glomerular injury
that does not have a specific cause. As its name indicates,
this type of glomerulonephritis is rapidly progressive, often
within a matter of months. The disorder involves focal
and segmental proliferation of glomerular cells and recruitment of monocytes (macrophages) with formation of
crescent-shaped structures that obliterate Bowman’s space.5
Rapidly proliferative glomerulonephritis may be caused by
a number of immunologic disorders, some systemic and
others restricted to the kidney. Among the diseases associated with this form of glomerulonephritis are immune
complex disorders such as SLE, the small vessel vasculitides (e.g., microscopic polyangiitis), and an immune disorder condition called Goodpasture’s syndrome.
Goodpasture’s syndrome, which is caused by antibodies to the glomerular basement membrane (GBM), accounts
for approximately 5% of cases of rapidly progressive glomerulonephritis. It is a rare disease and is associated with a
triad of pulmonary hemorrhage, iron-deficiency anemia,
and glomerulonephritis. All of these manifestations result from anti-GBM antibody deposition in the lungs and
glomeruli. The cause of the disorder is unknown, although
influenza infection and exposure to hydrocarbon solvent
(found in paints and dyes) have been implicated in some
persons, as have various drugs and cancers. There is a high
prevalence of certain human leukocyte antigen subtypes
(e.g., HLA-DRB1), suggesting a genetic predisposition.5
Treatment includes plasmapheresis to remove circulating
anti-GBM antibodies and immunosuppressive therapy
(i.e., corticosteroids and cyclophosphamide) to inhibit antibody production.
CHAPTER 35
Nephrotic Syndrome
Nephrotic syndrome is not a specific glomerular disease but
a constellation of clinical findings that result from increased
glomerular permeability to the plasma proteins (Fig. 35-10).
The glomerular derangements that occur with nephrosis
can develop as a primary disorder or secondary to changes
caused by systemic diseases such as diabetes mellitus, amyloidosis, and SLE. Among the primary glomerular lesions
leading to nephrotic syndrome are minimal change disease
(lipoid nephrosis), focal segmental glomerulosclerosis, and
membranous glomerulonephritis. The relative frequency
of these causes varies with age. In children younger than
15 years of age, nephrotic syndrome almost always is caused
by primary idiopathic glomerular disease, whereas in adults,
it often is a secondary disorder.5,43
The nephrotic syndrome is characterized by massive
proteinuria (>3.5 g/day) and lipiduria (e.g., free fat, oval
bodies, fatty casts), along with an associated hypoalbuminemia (<3 g/dL), generalized edema, and hyperlipidemia
(cholesterol >300 mg/dL).6,44–47 The initiating event in the
development of nephrosis is a derangement in the glomerular membrane that causes increased permeability to plasma
proteins. The glomerular membrane acts as a size and charge
barrier through which the glomerular filtrate must pass.
Any increased permeability allows protein to escape from
the plasma into the glomerular filtrate.
Generalized edema, which is a hallmark of nephrosis,
results from salt and water retention and a loss of serum
albumin below that needed to maintain the colloid osmotic pressure of the vascular compartment.5 The sodium
and water retention appears to be due to several factors,
including a compensatory increase in aldosterone, stimulation of the sympathetic nervous system, and a reduction
Glomerular damage
Increased permeability to proteins
Proteinuria ( 3.5 g/24 h)
Hypoproteinemia
Decreased plasma
oncotic pressure
Compensatory synthesis
of proteins by liver
Edema
Hyperlipidemia
FIGURE 35-10 Pathophysiology of the nephrotic syndrome.
Disorders of Renal Function
825
in secretion of natriuretic factors. Initially, the edema presents in dependent parts of the body such as the lower extremities, but becomes more generalized as the disease
progresses. Dyspnea due to pulmonary edema, pleural effusions, and diaphragmatic compromise due to ascites can
develop in persons with nephrotic syndrome.
Although the largest proportion of plasma protein
loss is in albumin, globulins also are lost. As a result, persons with nephrosis are particularly vulnerable to infections, particularly those caused by staphylococci and
pneumococci.5 This decreased resistance to infection probably is related to loss of both immunoglobulins and lowmolecular-weight complement components in the urine.
Many binding proteins also are lost in the urine. Consequently, the plasma levels of many ions (iron, copper, zinc),
hormones (thyroid and sex hormones), and drugs may be
low because of decreased binding proteins. Many drugs require protein binding for transport. Hypoalbuminemia
reduces the number of available protein-binding sites,
thereby producing a potential increase in the amount of
free (active) drug that is available.44
Thrombotic complications also have evolved as a risk
in persons with nephrotic syndrome.43 These disorders reflect a disruption in the function of the coagulation system
brought about by a loss of coagulation and anticoagulation
factors. Renal vein thrombosis, once thought to be a cause
of the disorder, is more likely a consequence of the hypercoagulable state.5 Other thrombotic complications include
deep vein thrombosis and pulmonary emboli.
The hyperlipidemia that occurs in persons with nephrosis is characterized by elevated levels of triglycerides
and low-density lipoproteins (LDLs). Levels of high-density
lipoproteins (HDLs) usually are normal. It is thought that
these abnormalities are related, at least in part, to increased
synthesis of lipoproteins in the liver secondary to a compensatory increase in albumin production.43 Because of the
elevated LDL levels, persons with nephrotic syndrome are
at increased risk for development of atherosclerosis.
Membranous Glomerulonephritis. Membranous glomerulonephritis is the most common cause of primary nephrosis
in adults, most commonly in their sixth or seventh decade.
The disorder is caused by diffuse thickening of the GBM due
to deposition of immune complexes. The disorder may be idiopathic or associated with a number of disorders, including
autoimmune diseases such as SLE, infections such as chronic
hepatitis B, metabolic disorders such as diabetes mellitus and
thyroiditis, and use of certain drugs such as gold compounds,
penicillamine, and captopril.5 Because of the presence of immunoglobulins and complement in the subendothelial deposits, it is thought that the disease represents a chronic
antigen–antibody complex–mediated disorder.
The disorder is treated with corticosteroids. Cytotoxic
drugs may be added to the treatment regimen. The progress
of the disease is variable; approximately one half of persons
sustain a slow but progressive loss of renal function.
Minimal Change Disease (Lipoid Nephrosis). Minimal
change disease is characterized by diffuse loss (through fusion) of the foot processes from the epithelial layer of the
glomerular membrane. The peak incidence is between 2
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and 6 years of age. The cause of minimal change nephrosis
is unknown; however, children in whom the disease develops often have a history of recent upper respiratory infections or of receiving routine immunizations.5 Although
minimal change disease does not progress to renal failure, it can cause significant complications, including predisposition to infection with gram-positive organisms, a
tendency toward thromboembolic events, hyperlipidemia,
and protein malnutrition. There usually is a dramatic response to corticosteroid therapy.5,43
Focal Segmental Glomerulosclerosis. Focal segmental glomerulosclerosis is characterized by sclerosis (i.e., increased
collagen deposition) of some but not all glomeruli, and in
the affected glomeruli, only a portion of the glomerular
tuft is involved.48 Although focal segmental sclerosis often
is an idiopathic syndrome, it may be associated with reduced
oxygen in the blood (e.g., sickle cell disease and cyanotic
congenital heart disease), human immunodeficiency virus
(HIV) infection, or intravenous drug abuse, or it may be a
secondary event reflecting glomerular scarring due to other
forms of glomerulonephritis or reflux nephropathy.5,6 The
presence of hypertension and decreased renal function distinguishes focal sclerosis from minimal change disease. The
disorder usually is treated with corticosteroids. Most persons with the disorder progress to end-stage renal disease
within 5 to 10 years.
Immunoglobulin A Nephropathy
Immunoglobulin A nephropathy (i.e., Buerger’s disease) is a
primary glomerulonephritis characterized by the presence
of glomerular IgA immune complex deposits. It can occur
at any age, but most commonly occurs with clinical onset
in the second and third decades of life.49 The disease occurs
more commonly in males than females and is the most
common cause of glomerular nephritis in Asians.
The disorder is characterized by the deposition of IgAcontaining immune complexes in the mesangium of the
glomerulus. Once deposited in the kidney, the immune
complexes are associated with glomerular inflammation.
The cause of the disorder is unknown. Some persons with
the disorder have elevated serum IgA levels. Recent studies
have focused on potential abnormalities of the IgA molecule as a factor in the pathogenesis of the disorder.49
Early in the disease, many persons with the disorder
have no obvious symptoms and are unaware of the problem. In these persons, IgA nephropathy is suspected during
routine screening or examination for another condition. In
other persons, the disorder presents with gross hematuria
that is preceded by upper respiratory tract infection, gastrointestinal tract symptoms, or a flulike illness. The hematuria usually lasts 2 to 6 days. Approximately one half of
the persons with gross hematuria have a single episode; the
remainder have gradual progression of glomerular disease
with recurrent episodes of hematuria and mild proteinuria.
Progression usually is slow, extending over several decades.
There is no satisfactory treatment for IgA nephropathy. The role of immunosuppressive drugs such as steroids
and cytotoxic drugs is not clear. There has been recent interest in the use of omega-3 fatty acids (fish oil) in delay-
ing the progression of the disease. Evidence suggests that
the daily use of fish oil in the diet may retard the progress
of the disease, particularly in persons with mildly impaired
renal function.49
CHRONIC GLOMERULONEPHRITIS
Chronic glomerulonephritis represents the chronic phase
of a number of specific types of glomerulonephritis.5 Some
forms of glomerulonephritis (e.g., poststreptococcal glomerulonephritis) undergo complete resolution, whereas
others progress at variable rates to chronic glomerulonephritis. Some persons who present with chronic glomerulonephritis have no history of glomerular disease. These cases
may represent the end result of relatively asymptomatic
forms of glomerulonephritis. Histologically, the condition
is characterized by small kidneys with sclerosed glomeruli.
In most cases, chronic glomerulonephritis develops insidiously and slowly progresses to end-stage renal disease over
a period of years (see Chapter 36).
GLOMERULAR LESIONS ASSOCIATED WITH
SYSTEMIC DISEASE
Many immunologic, metabolic, or hereditary systemic diseases are associated with glomerular injury. In some diseases, such as SLE and diabetes mellitus, the glomerular
involvement may be a major clinical manifestation. The
glomerular lesions associated with diabetes mellitus and
hypertension are discussed in this chapter.
Diabetic Glomerulosclerosis
Diabetic nephropathy, or kidney disease, is a major complication of diabetes mellitus. It affects approximately 30%
of persons with type 1 diabetes and accounts for 20% of
deaths in diabetic patients younger than 40 years of age.5
The glomerulus is the most commonly affected structure in diabetic nephropathy, evidenced by three glomerular syndromes: nonnephrotic proteinuria, nephrotic syndrome, and renal failure. Widespread thickening of the
glomerular capillary basement membrane occurs in almost
all persons with diabetes and can occur without evidence
of proteinuria.5 This is followed by a diffuse increase in
mesangial matrix, with mild proliferation of mesangial
cells. As the disease progresses, the mesangial cells impinge
on the capillary lumen, drastically reducing the surface
area for glomerular filtration. In nodular glomerulosclerosis, also known as Kimmelstiel-Wilson syndrome, there is
nodular deposition of hyaline in the mesangial portion of
the glomerulus. As the sclerotic process progresses in the
diffuse and nodular forms of glomerulosclerosis, there is
complete obliteration of the glomerulus, with impairment
of renal function.
Although the mechanisms of glomerular change in diabetes are uncertain, they are thought to represent enhanced or defective synthesis of the GBM and mesangial
matrix with an inappropriate incorporation of glucose into
the noncellular components of these glomerular structures.
Alternatively, hemodynamic changes that occur secondary
CHAPTER 35
to elevated blood glucose levels may contribute to the initiation and progression of diabetic glomerulosclerosis. It
has been hypothesized that elevations in blood glucose produce an increase in GFR and glomerular intracapillary pressure that leads to an enlargement of glomerular capillary
pores by a mechanism that is at least partly mediated by
angiotensin II. This enlargement impairs the size-selective
function of the membrane so that the protein content of
the glomerular filtrate increases, which in turn requires increased endocytosis of protein by the tubular endothelial
cells, a process that ultimately leads to nephron destruction
and progressive deterioration of renal function.50,51
The clinical manifestations of diabetic glomerulosclerosis are closely linked to those of diabetes. The increased
GFR that occurs in persons with early alterations in renal
function is associated with microalbuminuria, defined as urinary albumin excretion greater than 30 mg/24 hours and
no more than 300 mg/24 hours.51,52 Microalbuminuria is an
important predictor of future diabetic nephropathies.5,51 In
many cases, these early changes in glomerular function can
be reversed by careful control of blood glucose levels50,51
(see Chapter 43). Inhibition of angiotensin by angiotensinconverting enzyme inhibitors (e.g., captopril) has been
shown to have a beneficial effect, possibly by reversing increased glomerular pressure.6,51 Hypertension and cigarette
smoking have been implicated in the progression of diabetic nephropathy. Thus, control of high blood pressure
and smoking cessation are recommended as primary and
secondary prevention strategies in persons with diabetes.
Hypertensive Glomerular Disease
Hypertension can be viewed as both a cause and an effect of
kidney disease. Most persons with advanced kidney disease
have hypertension, and many persons with long-standing
hypertension eventually sustain changes in kidney function. Renal failure and azotemia occur in 1% to 5% of persons with long-standing hypertension (see Chapter 25).
Hypertension is associated with a number of changes in
glomerular structures, including sclerotic changes. As the
glomerular vascular structures thicken and perfusion diminishes, the blood supply to the nephron decreases, causing the kidneys to lose some of their ability to concentrate
the urine. This may be evidenced by nocturia. Blood urea
nitrogen levels also may become elevated, particularly during periods of water deprivation. Proteinuria may occur as
a result of changes in glomerular structure.
In summary, diseases of the glomerulus disrupt glomerular
filtration and alter the permeability of glomerular capillary
membrane to plasma proteins and blood cells. Glomerulonephritis is a term used to describe a group of diseases that
result in inflammation and injury of the glomerulus. These
diseases disrupt the capillary membrane and cause proteinuria, hematuria, pyuria, oliguria, edema, hypertension, and
azotemia. Almost all types of glomerulonephritis are caused
by immune mechanisms.
Glomerular diseases have been grouped into two categories: the nephritic and the nephrotic syndromes. The nephritic
syndrome evokes an inflammatory response in the glomeruli
Disorders of Renal Function
827
and is characterized by hematuria with red cell casts in the
urine, a diminished GFR, azotemia, oliguria, and hypertension.
The nephrotic syndrome affects the integrity of the glomerular
capillary membrane and is characterized by massive proteinuria, hypoalbuminemia, generalized edema, lipiduria, and
hyperlipidemia. Both conditions can lead to progressive loss of
glomerular function and eventual development of end-stage
renal disease. Among the secondary causes of glomerular kidney disease are diabetes and hypertension. Kidney disease is a
major complication of diabetes mellitus and is thought to be
related to hemodynamic changes associated with defective
synthesis of glomerular structures that occurs secondary to increased blood glucose levels. Hypertension is closely linked
with kidney disease, and kidney disease can be a cause or effect of elevated blood pressure.
Tubulointerstitial Disorders
After completing this section of the chapter, you should be able to
meet the following objectives:
✦ Cite a definition of tubulointerstitial kidney disease
✦ Differentiate between the defects in tubular function that
occur in proximal and distal tubular acidosis
✦ Explain the pathogenesis of kidney damage in
pyelonephritis
✦ Explain the vulnerability of the kidneys to injury caused
by drugs and toxins
Several disorders affect renal tubular structures, including the proximal and distal tubules. Most of these disorders also affect the interstitial tissue that surrounds the
tubules. These disorders, which sometimes are referred to
as tubulointerstitial disorders, include acute tubular necrosis
(see Chapter 36), renal tubular acidosis, pyelonephritis, and
the effects of drugs and toxins.
Tubulointerstitial renal diseases may be divided into
acute and chronic disorders. The acute disorders are characterized by their sudden onset and by signs and symptoms
of interstitial edema; they include acute pyelonephritis and
acute hypersensitivity reaction to drugs. The chronic disorders produce interstitial fibrosis, atrophy, and mononuclear infiltrates; most persons are asymptomatic until
late in the course of the disease. In the early stages, tubulointerstitial diseases commonly are manifested by fluid
and electrolyte imbalances that reflect subtle changes in
tubular function. These manifestations can include inability to concentrate urine, as evidenced by polyuria and nocturia; interference with acidification of urine, resulting in
metabolic acidosis; and diminished tubular reabsorption of
sodium and other substances.5
RENAL TUBULAR ACIDOSIS
Renal tubular acidosis (RTA) refers to a group of tubular
defects in reabsorption of bicarbonate ions (HCO3−) or excretion of hydrogen ions (H+) that result in acidosis and its
828
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Renal Function
subsequent complications, including metabolic bone disease, kidney stones, and growth failure in children. There
are two main types of RTA: proximal tubular disorders that
affect bicarbonate reabsorption, and distal tubular defects
that affect the secretion of fixed metabolic acids.53,54 A
third type of RTA results from aldosterone deficiency or resistance to its action that leads to impaired reabsorption of
sodium ions (Na+) with decreased elimination of H+ and
potassium ions (K+) (see Chapter 34). Renal acidosis also
occurs in renal failure (see Chapter 36).
Proximal Renal Tubular Acidosis. Proximal RTA involves
a defect in proximal tubular reabsorption of HCO3−, the
nephron site where 85% of filtered HCO3− is reabsorbed
(see Chapter 32). With the onset of impaired tubular
HCO3− absorption, there is a loss of HCO3− in the urine that
reduces plasma HCO3− levels. The concomitant loss of Na+
in the urine leads to contraction of the extracellular fluid
volume with increased aldosterone secretion and a resultant decrease in serum K+ levels (see Chapter 33). With
proximal tubular defects in acid-base regulation, the distal
tubular sites for secretion of the fixed acids into the urine
continue to function, and the reabsorption of HCO3− eventually resumes, albeit at a lower level of serum HCO3−.
Whenever serum levels rise above this decreased level,
HCO3− is lost in the urine. Persons with proximal RTA generally have plasma HCO3− levels greater than 15 mEq/L and
seldom develop severe acidosis.
Proximal RTA may occur as a hereditary or acquired
disorder and may involve an isolated defect in HCO3−
reabsorption or accompany other defects in proximal tubular function (Fanconi’s syndrome). Isolated defects in
HCO3− reabsorption are relatively rare. The term Fanconi’s
syndrome is used to describe a generalized proximal tubular dysfunction in which the RTA is accompanied by impaired reabsorption of glucose, amino acids, phosphate,
and uric acid. Children with Fanconi’s syndrome are likely
to have growth retardation, rickets, osteomalacia, and abnormal vitamin D metabolism in addition to mild acidosis associated with proximal RTA.
Children and infants with proximal RTA require alkali
therapy because of the high incidence of growth retardation
due to acidemia. Potassium supplements are also needed
because of increased loss of potassium that occurs with
alkali therapy. Adults may also require alkali therapy. Vitamin D and phosphate are appropriate treatments for rickets
and hypophosphatemia.
Distal Renal Tubular Acidosis. Distal RTA has its origin in
the distal convoluted tubule and the collecting duct where
about 15% of the filtered bicarbonate is reabsorbed. The
clinical syndrome of distal RTA includes hypokalemia, hyperchloremic metabolic acidosis, inability to acidify the
urine, nephrocalcinosis, and nephrolithiasis. Additional
features include osteomalacia or rickets.
Distal tubular RTA results from distal tubular defect in
H+ secretion with failure to acidify the urine. Because the
secretion of H+ in the distal tubules is linked to sodium reabsorption, failure to secrete H+ results in a net loss of
sodium bicarbonate in the urine. This results in contrac-
tion of fluids in the extracellular fluid compartment, a
compensatory increase in aldosterone levels, and development of hypokalemia. The persistent acidosis, which requires buffering by the skeletal system, causes calcium to
be released from bone. Increased losses of calcium in the
urine lead to increased levels of parathyroid hormone, osteomalacia, bone pain, impaired growth in children, and
development of kidney stones and nephrocalcinosis.
Long-term treatment of distal RTA requires alkali supplementation. Greater amounts are needed for children
because of the need for base deposition in growing bone
and because bicarbonate wastage is greater in children
than in adults. Alkali therapy will generally allow for correction of potassium wasting and hypokalemia. It also
decreases the calcium concentration in the urine and increases citrate excretion, both of which serve to decrease
the incidence of nephrocalcinosis and nephrolithiasis.54
PYELONEPHRITIS
Pyelonephritis refers to an inflammation of the kidney
parenchyma and renal pelvis. There are two forms of pyelonephritis: acute and chronic.
Acute Pyelonephritis
Acute pyelonephritis represents a patchy interstitial infectious inflammatory process, with abscess formation and
tubular necrosis. Gram-negative bacteria, including E. coli
and Proteus, Klebsiella, Enterobacter, and Pseudomonas species, are the most common causative agents. Gram-positive
bacteria are less commonly seen but include Enterococcus
faecalis and S. aureus. The infection usually ascends from
the lower urinary tract, with the exception of S. aureus,
which is usually spread through the bloodstream. Factors
that contribute to the development of acute pyelonephritis are catheterization and urinary instrumentation, vesicoureteral reflux, pregnancy, and neurogenic bladder. A
second less frequent and more serious type of acute pyelonephritis, called necrotizing pyelonephritis, is characterized
by necrosis of the renal papillae. It is particularly common
in persons with diabetes and may also be a complication
of acute pyelonephritis when there is significant urinary
tract obstruction.
The onset of acute pyelonephritis typically is abrupt,
with chills, fever, headache, back pain, tenderness over
the costovertebral angle, and general malaise. It usually is
accompanied by symptoms of bladder irritation, such as
dysuria, frequency, and urgency. Pyuria occurs but is not
diagnostic because it also occurs in lower UTIs. The development of necrotizing papillitis is associated with a
much poorer prognosis. These persons have evidence of
overwhelming sepsis with frequent development of renal
failure.
Acute pyelonephritis is treated with appropriate antimicrobial drugs. Unless obstruction or other complications occur, the symptoms usually disappear within several
days. Hospitalization during initial treatment may be necessary. Depending on the cause, recurrent infections are
possible.
CHAPTER 35
Chronic Pyelonephritis
Chronic pyelonephritis represents a progressive process.
There is scarring and deformation of the renal calices and
pelvis5 (Fig. 35-11). The disorder appears to involve a bacterial infection superimposed on obstructive abnormalities or
vesicoureteral reflux. Chronic obstructive pyelonephritis is
associated with recurrent bouts of inflammation and scarring, which eventually lead to chronic pyelonephritis. Reflux, which is the most common cause of chronic pyelonephritis, results from superimposition of infection on
congenital vesicoureteral reflux or intrarenal reflux. Reflux
may be unilateral with involvement of a single kidney or bilateral leading to scarring and atrophy of both kidneys with
the eventual development of chronic renal insufficiency.
Chronic pyelonephritis may cause many of the same
symptoms as acute pyelonephritis, or its onset may be insidious. Loss of tubular function and of the ability to concentrate urine give rise to polyuria and nocturia, and mild
proteinuria is common. Severe hypertension often is a
contributing factor in the progress of the disease. Chronic
pyelonephritis is a significant cause of renal failure. It is
thought to be responsible for 11% to 20% of all cases of
end-stage renal disease.5
DRUG-RELATED NEPHROPATHIES
Drug-related nephropathies involve functional or structural changes in the kidneys that occur after exposure to
a drug. The kidneys are exposed to a high rate of delivery
of any substance in the blood because of their large blood
flow and high filtration pressure. The kidneys also are ac-
FIGURE 35-11 Chronic pyelonephritis. Marked dilatation of calices
caused by inflammatory destruction of papillae, with atrophy and
scarring of the overlying cortex. (Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 905] Philadelphia: Lippincott-Raven)
Disorders of Renal Function
829
tive in the metabolic transformation of drugs and therefore are exposed to a number of toxic metabolites. The
tolerance to drugs varies with age and depends on renal
function, state of hydration, blood pressure, and the pH
of the urine. Because of a decrease in physiologic function, elderly persons are particularly susceptible to kidney damage caused by drugs and toxins. The dangers of
nephrotoxicity are increased when two or more drugs
capable of producing kidney damage are given at the
same time.
Drugs and toxic substances can damage the kidneys
by causing a decrease in renal blood flow; obstructing
urine flow; directly damaging tubulointerstitial structures;
or producing hypersensitivity reactions.55
Some drugs such as diuretics, high-molecular-weight
radiocontrast media, the immunosuppressive drugs cyclosporine and tacrolimus, and the nonsteroidal antiinflammatory drugs can cause acute prerenal failure by decreasing
renal blood flow (see Chapter 36). Persons at risk are those
who already have compromised renal blood flow. Other
drugs such as sulfonamides and vitamin C (due to oxalate
crystals) can form crystals that cause kidney damage by obstructing urine flow within the tubules.
Acute drug-related hypersensitivity reactions produce
tubulointerstitial nephritis, with damage to the tubules
and interstitium. This condition was observed initially in
persons who were sensitive to the sulfonamide drugs; currently, it is observed most often with the use of methicillin
and other synthetic antibiotics, and with the use of furosemide and the thiazide diuretics in persons sensitive to
these drugs. The condition begins approximately 15 days
(range, 2 to 40 days) after exposure to the drug.56 At the
onset, there is fever, eosinophilia, hematuria, mild proteinuria, and in approximately one fourth of cases, a rash.
In approximately 50% of cases, signs and symptoms of
acute renal failure develop. Withdrawal of the drug commonly is followed by complete recovery, but there may be
permanent damage in some persons, usually in older persons. Drug nephritis may not be recognized in its early
stage because it is uncommon.
Chronic analgesic nephritis, which is associated with
analgesic abuse, causes interstitial nephritis with renal papillary necrosis. When first observed, it was attributed to
phenacetin, a then-common ingredient of over-the-counter
medications containing aspirin, phenacetin, and caffeine.
Although phenacetin is no longer contained in these preparations, it has been suggested that other ingredients, such
as aspirin and acetaminophen, also may contribute to the
disorder. How much analgesic it takes to produce papillary
necrosis is unknown.
Nonsteroidal anti-inflammatory drugs (NSAIDs) also
have the potential for damaging renal structures, including
medullary interstitial cells. Prostaglandins (particularly PGI2
and PGE2) contribute to regulation of tubular blood flow.56
The deleterious effects of NSAIDs on the kidney are thought
to result from their ability to inhibit prostaglandin synthesis. Persons who are particularly at risk are the elderly because of age-related changes in renal function, persons who
are dehydrated or have a decrease in blood volume, and persons with preexisting kidney disease or renal insufficiency.
830
UNIT VIII
Renal Function
In summary, tubulointerstitial diseases affect the tubules and
the surrounding interstitium of the kidneys. These disorders include renal tubular acidosis, chronic pyelonephritis, and the effects of drugs and toxins. Renal tubular acidosis describes a
form of systemic acidosis that results from tubular defects in
bicarbonate reabsorption or hydrogen ion secretion. Pyelonephritis, or infection of the kidney and kidney pelvis, can
occur as an acute or a chronic condition. Acute pyelonephritis
typically is caused by ascending bladder infections or infections that come from the bloodstream; it usually is successfully
treated with appropriate antimicrobial drugs. Chronic pyelonephritis is a progressive disease that produces scarring and
deformation of the renal calices and pelvis. Drug-induced impairment of tubulointerstitial structure and function usually is
the result of direct toxic injury, decreased blood flow, or hypersensitivity reactions.
stage IV, hematogenous metastasis most commonly involves the lung. Bilateral kidney involvement occurs in
5% to 10% of cases.
The common presenting signs are a large asymptomatic abdominal mass and hypertension. The tumor is
often discovered inadvertently, and it is not uncommon
for the mother to discover it while bathing the child.
Some children may present with abdominal pain, vomiting, or both. Microscopic and gross hematuria is present
in 10% to 25% of children. CT scans are used to confirm
the diagnosis.
Treatment involves surgery, chemotherapy, and sometimes radiation therapy. Long-term survival rates have increased to greater than 80% with an aggressive treatment
plan.57,58
ADULT KIDNEY CANCER
Neoplasms
After completing this section of the chapter, you should be able to
meet the following objectives:
✦ Characterize Wilms’ tumor in terms of age of onset,
possible oncogenic origin, manifestations, and treatment
✦ Cite the risk factors for renal cell carcinoma, describe the
manifestations, and explain why the 5-year survival rate
has been so low
There are two major groups of renal neoplasms: embryonic kidney tumors (i.e., Wilms’ tumor), which occur
during childhood, and adult kidney cancers.
WILMS’ TUMOR
Wilms’ tumor (i.e., nephroblastoma) is one of the most
common primary neoplasms of young children. The median age at time of diagnosis of unilateral Wilms’ tumor is
approximately 3 to 5 years.57,58 Classically, the tumor is
composed of all three embryonic cell types: blastemic, stromal, and epithelial. An important feature of Wilms’ tumor
is its association with other congenital anomalies, the most
frequent being those affecting genitourinary structures.
Several chromosomal abnormalities have been associated
with Wilms’ tumor. Deletions involving at least two loci
on chromosome 11 have been found in approximately
20% of children with Wilms’ tumor.57
Wilms’ tumor usually is a solitary mass that occurs in
any part of the kidney. It usually is sharply demarcated
and variably encapsulated. The tumors grow to a large
size, distorting kidney structure. The tumors usually are
staged using the Wilms’ Tumor Study Group classification.57 Stage I tumors are limited to the kidney and can be
excised with the capsular surface intact. Stage II tumors
extend into the kidney but can be excised. In stage III, extension of the tumor is confined to the abdomen, and in
Adult kidney cancer accounts for 2% to 3% of all new cancers. Men are affected about twice as often as women, and
the mean age at time of diagnosis is about 60 years.59 The
increased use of imaging procedures such as ultrasonography, CT scanning, and magnetic resonance imaging (MRI)
has contributed significantly to earlier diagnosis and more
accurate staging of kidney cancers.60
Renal cell carcinoma originates in the renal cortex and
accounts for approximately 80% to 85% of kidney tumors,
with transitional or squamous cell cancers of the renal
pelvis accounting for most of the remaining cancers.61 The
cause of renal cell carcinoma remains unclear. Some of
these tumors may occur as a result of chronic irritation
associated with kidney stones. Epidemiologic evidence
suggests a correlation between smoking and kidney cancer. Obesity also is a risk factor, particularly in women.61
Additional risk factors include occupational exposure to
petroleum products, heavy metals, and asbestos. The risk
for renal cell carcinoma also is increased in persons with
acquired cystic kidney disease associated with chronic renal insufficiency.60,61 Most cases of renal cell carcinoma
occur without a recognizable hereditary pattern. However,
there are several rare forms of renal cell cancer that are
characterized by an autosomal dominant pattern of inheritance, young age at onset (third and fourth decade),
and bilateral or multifocal tumors.60,61
Kidney cancer is largely a silent disorder during its
early stages, and symptoms usually denote advanced disease. Presenting features include hematuria, costovertebral
pain, presence of a palpable flank mass, polycythemia, and
fever. Hematuria, which occurs in 70% to 90% of cases, is
the most reliable sign. It is, however, intermittent and may
be microscopic; as a result, the tumor may reach considerable size before it is detected. In approximately one third
of cases, metastases are present at the time of diagnosis.
Kidney cancer is suspected when there are findings of
hematuria and a renal mass. Ultrasonography, CT scanning, excretory urography, and renal angiography are used
to confirm the diagnosis. MRI with intravenous gadolinium may be used when involvement of the inferior vena
cava is suspected.
CHAPTER 35
Surgery (radical nephrectomy with lymph node dissection) is the treatment of choice for all resectable tumors. Nephron-sparing surgery may be done when both
kidneys are involved or when the contralateral kidney is
threatened by an associated disease such as hypertension
or diabetes mellitus. Single-agent and combination
chemotherapy have been used with limited success. Immunotherapy involving interferon-alfa and interleukin-2
has been used with some success.61 The 5-year survival rate
for stage I disease ranges from 65% to 85%; 45% to 80%
for stage II disease; 15% to 35% for stage III disease; and
0% to 10% for stage IV disease.60
In summary, there are two major groups of renal neoplasms:
embryonic kidney tumors (i.e., Wilms’ tumor) that occur during
childhood and adult renal cell carcinomas. Wilms’ tumor is the
most common malignant tumor of children. The most common presenting signs are a large abdominal mass and hypertension. Treatment is surgery, chemotherapy, and sometimes
radiation therapy. The long-term survival rate for children with
Wilms’ tumor is approximately 90% with an aggressive plan
of treatment.
Adult kidney cancers account for 2% of all cancers. Renal
cell carcinoma is the most frequent type of kidney cancer.
These tumors are characterized by a lack of early warning
signs, diverse clinical manifestations, and resistance to chemotherapy and radiation therapy. Because of the lack of early
warning signs, the tumors often are far advanced at the time
of diagnosis. Diagnostic methods include ultrasonography
and CT scans. The treatment of choice is surgical resection.
Prognosis depends on the stage of the cancer; the 5-year survival rate for stage I tumors is 65% to 85%, and for stage IV
tumors, it is 0% to 10%.
REVIEW EXERCISES
A 6-year-old boy is diagnosed with glomerulonephritis
secondary to a streptococcal throat infection. He had
been diagnosed with nephrotic syndrome several months
ago. At this time, the following manifestations are noted:
a decrease in urine output, increasing lethargy, hyperventilation, and generalized edema. Trace amounts of
protein are detected in his urine. Blood analysis reveals
the following: pH = 7.35, HCO3 = 18 mEq/L, hematocrit
= 29%, Na = 132 mEq/L, K = 5.6 mEq/L, BUN = 62 mg/dL,
creatinine = 4.1 mg/dL, albumin = 2 g/dL.
A. What is the probable cause of this boy’s glomerular
disease?
B. Use the lab values in the appendix to interpret his
lab values. Which values are significant and why?
C. Is he progressing to uremia? How can you tell?
A 26-year-old woman makes an appointment with her
health care provider complaining of urinary frequency,
urgency, and burning. She reports that her urine is cloudy
and smells abnormal. Her urine is cultured, and she is
given a prescription for antibiotics.
Disorders of Renal Function
831
A. What is the most likely cause of the woman’s
symptoms?
B. What microorganism is most likely responsible for
the infection?
C. What factors may have predisposed to this disorder?
D. What could this woman do to prevent future
infection?
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