BRS – Pediatrics: Nephrology and Urology

Source: BRS Pediatrics, 2019

I. Fluids, Electrolytes, and Dehydration

A. General principles
1. The most common cause of acute fluid and electrolyte imbalance is acute diarrhea with dehydration.
2. Worldwide, acute diarrheal diseases are among the leading causes of childhood morbidity and mortality.
B. Total body fluid requirement is the sum of a patient’s maintenance fluid needs, replacement of prior fluid losses (i.e., deficits), and replacement of ongoing losses, if any.
1. Maintenance water and electrolyte calculations are designed to balance the usual daily losses of water and salts that occur as a result of normal daily metabolic activities. These losses take both measurable forms (sensible losses), such as urinary losses, and less readily measurable but still clinically significant forms (insensible losses), such as losses from the skin, lungs, and gastrointestinal (GI) tract.
a. Maintenance water requirement is approximately 1500 mL/m2/day for children. Water requirements for infants and premature infants vary with the birth weight and postnatal age.
b. Maintenance water requirement may alternatively be calculated from the patient’s weight.
1. 100 mL/kg/day for the first 10 kg of body weight
2. 50 mL/kg/day for the second 10 kg of body weight
3. 20 mL/kg/day for each kg above the first 20 kg of body weight
c. Maintenance fluids should be increased if the patient has increased insensible losses, such as respiratory distress and fever (i.e., about a 10% increase for every degree of temperature).
d. Maintenance sodium (Na+) requirement is approximately 2–3 mEq/kg/day.
e. Maintenance potassium (K+) requirement is approximately 2 mEq/kg/day.
2. Deficit fluid calculations are designed to replace abnormal losses of water and salts caused by pathologic states, such as diarrhea and vomiting. Deficit fluids are calculated as follows: Fluid deficit (L) = pre-illness weight (kg) − current weight (kg).
3. Ongoing loss calculations are designed to replace additional losses of water and salts after the patient’s initial evaluation (e.g., ongoing vomiting or diarrhea, nasogastric tube aspirate). These ongoing losses are replaced milliliter for milliliter.
C. Dehydration may be classified by both the initial serum Na+ level and by the degree of dehydration.
1. Classification by serum sodium concentration
a. Hyponatremic dehydration (Na+ < 130 mmol/L)
b. Isonatremic dehydration (Na+ = 130–150 mmol/L)
c. Hypernatremic dehydration (Na+ > 150 mmol/L)
2. Classification by degree of dehydration
a. Mild dehydration (3–5%) is associated with normal pulse rate and quality, flat fontanelle, dry mucous membranes, normal skin turgor, normal capillary refill, and normal to decreased urine output.
b. Moderate dehydration (7–10%) is associated with mild tachycardia with a weak pulse, flat fontanelle, deep set eyes, reduced tears, dry mucous membranes, skin tenting, and capillary refill of about of 2 seconds, in a patient with decreased urine output.
c. Severe dehydration (≥10%) is associated with tachycardia and feeble pulse, sunken fontanelle, sunken eyes, no tears, parched and cracked lips and buccal mucosa,

clammy skin, and capillary refill >3 seconds, in a patient with lethargy and anuria.
D. Parenteral rehydration should occur in two phases:
1. Emergency phase
a. The goal of the emergency phase is to restore or maintain the intravascular volume to ensure perfusion of vital organs.
b. The emergency phase is the same for all patients, regardless of the patient’s initial serum sodium level.
c. 20 mL/kg boluses of intravenous (IV) solutions with a high enough oncotic load (e.g., normal saline or lactated Ringer solution) are commonly used.
2. Repletion phase
a. The goal of the repletion phase is a more gradual correction of the patient’s water and electrolyte deficits.
b. Patients with the acute onset of hyponatremic or isonatremic dehydration generally have their fluid and electrolyte deficits replaced over 24 hours. Chronic hyponatremia should be corrected much more slowly.
c. Patients with hypernatremic dehydration generally have their fluid and electrolyte deficits replaced more slowly, usually over 48 hours, to minimize the risk of cerebral edema that may accompany rapid fluid correction.
E. Oral rehydration therapy (ORT)
1. ORT may be an effective, safe, and inexpensive alternative to IV rehydration therapy.
2. Oral rehydration salt (ORS) solutions are balanced mixtures of glucose and electrolytes for use in treating and preventing dehydration, potassium depletion, and base deficits caused by diarrhea.
3. ORT is based on the principle that the intestinal absorption of sodium and other electrolytes is enhanced by the active absorption of glucose (coupled cotransport mechanism). This coupled cotransport process of intestinal absorption continues to function normally during secretory diarrhea, whereas other pathways of intestinal absorption of sodium are impaired.
4. ORT is inappropriate for patients with severe life-threatening dehydration, for patients with paralytic ileus or GI obstruction, and for patients with extremely rapid stool losses or repeated severe emesis losses.

II. Hematuria
A. Definition. Hematuria is defined as the presence of red blood cells (RBCs) in the urine. Hematuria may be seen on voiding (gross hematuria) or only on urinalysis (microscopic hematuria). Microscopic hematuria is defined as ≥5–6 RBCs per high-power field (HPF) detected on two or more consecutive samples.
B. Epidemiology. Approximately 5% of school children have microscopic hematuria detected on a single voided urine sample, but only 0.5–2% have persistent microscopic hematuria.
C. Clinical significance. Microscopic hematuria may be an indicator of a serious medical condition such as a tumor or chronic glomerulonephritis or may be of no serious medical consequence. Discolored urine may not be from blood in the urine. See Figure 11-1 for clues regarding the causes of discolored urine. The differential diagnosis of hematuria is outlined in Figure 11-2.
D. Evaluation (Figure 11-1). Detection of hematuria may be by urinary dipstick or by microscopy. Urinary dipstick detects the presence of hemoglobin or myoglobin in the urine. False-negative results may occur with ascorbic acid (vitamin C) ingestion. Microscopic urinalysis may also provide helpful clues. When RBCs are present on microscopic examination, careful examination of RBC morphology and identification of other urine elements, such as casts or bacteria, may be extremely helpful in determining the cause of the hematuria.
1. RBC morphology
a. RBCs originating in the glomerulus are dysmorphic in character, often with blebs in the RBC membrane.
b. RBCs that appear to be normal biconcave disks usually originate in the lower urinary tract.
2. RBC casts are diagnostic of glomerular bleeding, which usually occurs in acute or chronic glomerulonephritis.
a. Crystals may be indicative of renal stone disease.
b. Large numbers of RBCs (especially in the presence of dysuria) may indicate acute hemorrhagic cystitis, which may result from bacterial infections, viral infections (e.g., adenovirus), or chemotherapeutic agents (e.g., cyclophosphamide).

FIGURE 11-1 An approach to red urine. RBC = red blood cell; U/A = urinalysis.

FIGURE 11-2 Differential diagnosis of hematuria.

III. Proteinuria
A. While a small amount of protein is normally present in the urine, proteinuria greater than 100 mg/m2/day or an elevated urine total protein/creatinine ratio are considered pathologic.
B. Detection
1. Urinary dipstick is the most frequently used method of screening for proteinuria and detects variable levels of albuminuria.
a. False positives may result if the urine is very concentrated (specific gravity > 1.025) or alkaline (pH ≥ 7.0), or if the patient has received certain medications (e.g., penicillin, aspirin, IV contrast imaging agents, oral hypoglycemic agents).
b. False negatives may result if the urine is very dilute.
2. Twenty-four–hour urinary protein collection (normal is <100 mg/m2/day) is the most accurate method of detecting proteinuria but is very difficult to obtain in children. Instead, a random spot urine total protein-to-creatinine ratio (TP/CR) is usually performed. An early morning sample correlates well with 24-hour urinary protein excretion.
a. Normal urine TP/CR for infants of age 6–24 months is <0.5.
b. Normal urine TP/CR for children of age >2 years is <0.2.
C. Epidemiology. Up to 10% of children have a single positive dipstick test for proteinuria at some point; however, <1% have persistent proteinuria on repeated dipstick evaluations.
D. Classification
1. Benign transient proteinuria. Increased urinary protein excretion may sometimes be associated with vigorous exercise, fever, dehydration, and congestive heart failure (CHF).
2. Orthostatic proteinuria
a. Certain children and adults (especially athletic individuals) have increased urinary protein excretion while upright but not while supine.
b. Orthostatic proteinuria is usually a benign condition, and its confirmation eliminates the need for further workup.
c. The presence of orthostatic proteinuria is diagnosed with an elevated afternoon urine TP/CR and a normal first morning urine TP/CR.
3. Persistent pathologic proteinuria
a. Persistent pathologic proteinuria may be associated with significant renal disease and is considered a marker for progression of renal disease.
b. Generally, the greater the magnitude of the proteinuria, the more serious the renal disease. The greatest amounts of proteinuria are seen in patients with nephrotic syndrome [see section VI].
c. Persistent pathologic proteinuria may have a glomerular origin or a tubular origin. Glomerular proteinuria is more common.
1. Glomerular proteinuria is caused by increased permeability of the glomerular capillaries to large molecular weight proteins, as seen in glomerulonephritis [see section V] and in minimal change nephrotic syndrome.
2. Tubular proteinuria results from decreased reabsorption of low molecular weight proteins by the tubular epithelial cells, or by the addition of inflammatory proteins to the tubular urine.
a. Examples of tubular proteinuria include interstitial nephritis, ischemic renal injury (acute tubular necrosis, acute kidney injury [AKI]), and tubular damage resulting from nephrotoxic drugs.
b. Laboratory findings include elevated levels of urinary β2-microglobulin,

a good marker for tubular proteinuria among others. This small molecule, which is freely filtered at the glomerulus, is normally almost completely reabsorbed by the tubular epithelial cells. Its presence therefore signifies tubular injury. Glucosuria and aminoaciduria may also accompany diffuse injury to the tubular epithelial cells.
E. Evaluation of proteinuria (Figure 11-3)

FIGURE 11-3 Evaluation of proteinuria.

IV. Hypertension
A. Definitions
1. Normal blood pressures during childhood depend on the child’s age, sex, height, and weight. Standards are based on upper arm blood pressures (blood pressures in the legs are generally higher than in the arms).
2. Normal systolic and diastolic blood pressures are defined as blood pressure less than the 90th percentile.
3. Prehypertension is between the 90th and 95th percentiles for age.
B. Classification. Hypertension is divided into categories based on severity and etiology.
1. Hypertension is defined as the average of three separate blood pressures that are greater than the 95th percentile for age.
2. Stage 1 hypertension is defined as systolic or diastolic blood pressures between the 95th and 99th percentiles + 5 mm Hg.
3. Stage 2 hypertension is defined as systolic or diastolic blood pressures > 99th percentile + 5 mm Hg.
4. Malignant hypertension is hypertension associated with evidence of end organ damage, such as retinal hemorrhages, papilledema, seizures, and coronary artery disease (in adults).
5. Essential hypertension is defined as hypertension without a clear etiology.
6. Secondary hypertension is hypertension that has a recognizable cause (e.g., renal parenchymal disease, coarctation of the aorta). Most hypertension in childhood is secondary hypertension.
C. Measurement
1. Blood pressure cuff size
a. It is critical to use the proper size cuff. A cuff that is too small will give factitiously elevated blood pressures, and a cuff that is too large will give falsely depressed blood pressures.
b. The cuff bladder should measure two-thirds of the length of the arm from the shoulder to the elbow.
2. Position
a. Blood pressure in infants should be measured in the supine position.
b. Blood pressure in children and adolescents should be measured in the seated position with the fully exposed right arm resting on a supportive surface at heart level.
D. Etiology (Table 11-1). The causes of hypertension vary with the child’s age.
1. In neonates and young infants, the most common causes include renal artery embolus after umbilical artery catheter placement, coarctation of the aorta, congenital renal disease, and renal artery stenosis.
2. In children 1–10 years of age, the most common causes include renal diseases and coarctation of the aorta.
3. In adolescents, the most common causes include renal diseases and essential hypertension.
E. Clinical features. Clinical presentations of hypertension also vary with the child’s age. Some children, like some adults, are asymptomatic.
1. Infants may present with nonspecific signs and symptoms including irritability, vomiting, failure to thrive, seizures, or even CHF if the hypertension is severe.
2. Children with malignant hypertension, especially of acute onset, may develop headaches, seizures, and stroke.

3. Children with chronic hypertension may have growth retardation and poor school performance.
F. Evaluation. Because most children with hypertension have secondary hypertension, the cause of the hypertension is usually identified through a careful history (including family history and birth history), physical examination, and diagnostic testing. Testing is guided by the most likely causes of hypertension on the basis of the child’s age and clinical presentation.
1. Physical examination
a. All children should undergo an assessment of growth and careful, accurate measurements of four-limb blood pressures to evaluate for coarctation of the aorta (see Chapter 8, section III.F). In coarctation, hypertension is usually noted in the right arm with lower blood pressures in the legs.
b. In children, a careful fundoscopic examination may show retinal hemorrhages, papilledema, or in long-standing hypertension, arteriovenous nicking.
c. Other important physical findings include signs of CHF, café-au-lait spots as seen in neurofibromatosis, abdominal masses, abdominal bruits, and ambiguous genitalia.
2. Laboratory evaluation and imaging
a. Initial evaluation should include a complete blood count (CBC), electrolyte panel, blood urea nitrogen (BUN) and creatinine, urinalysis, plasma renin and aldosterone levels, thyroid panel, chest radiograph, and renal ultrasound. A urine microalbumin/creatinine ratio is useful in detecting early glomerular injury from the hypertension as a sign of end organ damage. (Note that the microalbumin/creatinine ratio is a very sensitive test for detecting proteinuria and is used to detect early glomerular proteinuria in hypertension. The protein/creatinine ratio becomes positive when a patient has more overt proteinuria and is therefore an indicator for more severe damage.)
b. If the initial evaluation is suggestive, further studies may include plasma catecholamines, measurement of plasma and urinary steroids, and echocardiography. Computer tomography (CT) angiography, especially in the setting of discrepant kidney sizes, can be performed to rule out renal artery stenosis.
c. Ambulatory blood pressure monitoring is very useful to rule out anxiety (“white coat hypertension”) before embarking on more expensive or invasive diagnostic testing.
G. Management. The treatment of hypertension should be aimed at curative therapies, whenever possible. In chronic hypertension, the ultimate goal is to maintain the child’s blood pressure below the 90th percentile for age.
1. If a specific, treatable cause of hypertension is identified, directed management, such as surgical correction of a coarctation of the aorta, treatment of hyperthyroidism, or removal of a catecholamine-secreting tumor, is performed as a cure.
2. If the child appears to have essential hypertension, the initial approach is conservative through implementation of a diet with no added salt, and if appropriate, weight loss. This approach requires frequent monitoring and encouragement.
3. If the child has underlying renal disease or more significant hypertension (e.g., stage 2), or if conservative hypertension treatment has failed, antihypertensive medications are used.
4. Hypertensive emergencies (e.g., seizures, severe headache, stroke, fundoscopic changes, CHF) require prompt therapy with IV antihypertensives.

Table 11-1
Etiology of Hypertension in Children

Essential hypertension*
No identifiable cause, but heredity, salt sensitivity, obesity, and stress all may play a role
Renal diseases
Glomerulonephritis Reflux nephropathy Renal dysplasia Polycystic kidney disease Renal trauma Obstructive uropathy
Hemolytic uremic syndrome
Renal vascular lesions
Renal artery stenosis or embolus Renal vein thrombosis Vasculitis
Neurofibromatosis
Cardiac disease
Coarctation of the aorta
Endocrine disorders
Neuroblastoma Pheochromocytoma Congenital adrenal hyperplasia Hyperthyroidism Hyperparathyroidism Hyperaldosteronism
Cushing syndrome
Central nervous system disorders
Increased intracranial pressure (e.g., hemorrhage, tumor) Encephalitis
Familial dysautonomia
Drug-related causes
Corticosteroids
Illicit drugs (e.g., amphetamines, cocaine, PCP) Anabolic steroids
Cold remedies Oral contraceptives
Genetic causes
Liddle syndrome Gordon syndrome
Apparent mineralocorticoid excess syndrome Glucocorticoid remediable
Aldosteronism
Miscellaneous causes
Wilms tumor
Blood pressure cuff too small Anxiety
Pain
Fractures and orthopedic traction Hypercalcemia
*Essential hypertension is rare in young children. All children with hypertension should have a careful evaluation to determine the cause of the hypertension.
PCP = phencyclidine.

V. Glomerulonephritis
A. Definition. Glomerulonephritis refers to a group of diseases that cause inflammatory changes in the glomeruli.
B. Etiology. Causes are varied but generally involve immune-mediated injury to the glomerulus. Various antigens can stimulate immune complex deposition or formation within the glomerulus.
C. Classification
1. Primary glomerulonephritis refers to a disease process limited to the kidney.
2. Secondary glomerulonephritis refers to a disease process that is part of a systemic disease (e.g., systemic lupus erythematosus [SLE]).
D. Clinical features. The presentation of glomerulonephritis is variable.
1. Some patients present with an acute “nephritic” syndrome which is characterized by gross hematuria, “cola-colored” urine, hypertension, and occasionally signs of fluid overload from renal insufficiency.
2. Some patients may present with glomerulonephritis associated with nephrotic syndrome
with heavy proteinuria, hypercholesteremia, and edema.
3. Some patients may be relatively asymptomatic, in whom glomerulonephritis is only detected as part of the evaluation of microscopic hematuria, proteinuria, or hypertension.
E. Laboratory evaluation. Laboratory studies should be performed promptly to avoid missing key transient abnormalities (e.g., transient decrease in serum complement is seen in poststreptococcal glomerulonephritis [PSGN]).
1. Initial evaluation should include urinalysis (to look for casts and to evaluate RBC morphology), urinary TP/CR (to quantify proteinuria), blood chemistries (including electrolyte panel, BUN, creatinine, serum albumin, liver enzymes, and cholesterol), serum complement components, antibody testing (antinuclear antibody [ANA], antineutrophil cytoplasmic antibody panel [ANCA], antistreptolysin O [ASO] and anti- DNase B [ADB]), and an IgA level if IgA nephropathy is suspected.
2. Additional evaluation, should the history be suggestive, may include human immunodeficiency virus (HIV) testing and hepatitis C and hepatitis B serologies to evaluate for causes of postinfectious glomerulonephritis.
F. Common types of glomerulonephritis in children
1. Post-Streptococcal Glomerulonephritis (PSGN)
a. Epidemiology. PSGN is the most common form of acute glomerulonephritis that occurs in school-age children. (Note that some of the other less common causes of postinfectious glomerulonephritis include malaria, HIV, hepatitis B and C, and congenital syphilis.) PSGN is rare before 2 years of age.
b. Clinical features
1. PSGN typically develops 8–14 days after an infection of the skin or pharynx with a nephritogenic strain of group A β-hemolytic streptococcus. The latency period after impetigo may be as long as 21–28 days.
2. Hematuria (often gross hematuria), proteinuria (rarely of nephrotic proportion), and hypertension with signs of fluid overload (e.g., edema) are common clinical features.
3. Low serum complement (C3) is present but transient and normalizes within 8–12 weeks.
4. The degree of impairment of renal function is variable and usually normalizes within 6–8 weeks. Severe renal failure is rare.
c. Diagnosis. Diagnosis is on the basis of clinical features and laboratory findings,

including evidence of prior streptococcal infection.
1. Detection of prior streptococcal infection
a. ASO titer is positive in 90% of children after streptococcal pharyngitis, but is positive in only 50% of patients with impetigo.
b. ADB titer is reliably positive after respiratory or skin infections with streptococcus.
2. Other diagnostic tests should include urinalysis, serum complement levels, renal ultrasound, tests of renal function, serum albumin, and serum cholesterol if the serum albumin is depressed.
3. Renal biopsy is indicated only if the patient has significant renal impairment or nephrotic syndrome, or if the serum complement fails to normalize within 12 weeks. Biopsy typically shows mesangial cell proliferation and increased mesangial matrix, as well as very large subepithelial deposits (humps) on electron microscopy, and C3 and IgG deposits on immunofluorescent microscopy.
d. Management. Treatment is supportive in most cases and includes fluid restriction, antihypertensive medications, and dietary restriction of protein, sodium, potassium, and phosphorus, as dictated by the level of renal functional impairment.
e. Prognosis is excellent with complete recovery in most patients.
f. Prompt antibiotic treatment of infections with nephritogenic strains of group A β-hemolytic streptococcus does not reduce the risk of PSGN, although it will reduce the risk of rheumatic fever (see Chapter 16, section VI and Chapter 7, section IX.A.5.f).
2. IgA nephropathy (Berger disease)
a. Epidemiology
1. IgA nephropathy is the most common type of chronic glomerulonephritis worldwide. It typically presents in the second or third decade of life.
2. It is more prevalent in Asia and Australia and in Native Americans, and it is rare in African Americans.
b. Etiology. The cause is poorly understood but may relate to abnormal clearance and formation of IgA immune complexes containing IgA molecules that are abnormally glycosylated.
c. Clinical features. Clinical findings classically include recurrent bouts of gross hematuria associated with respiratory infections. However, not all patients experience gross hematuria. Transient acute renal failure may occur in some patients. Microscopic hematuria is present in between the bouts of gross hematuria. The presence of heavy proteinuria and elevated serum creatinine are poor prognostic signs.
d. Diagnosis. Renal biopsy, which shows mesangial proliferation and increased mesangial matrix on light microscopy, is the basis of diagnosis. Immunofluorescent microscopy reveals mesangial deposition of IgA as the dominant immunoglobulin. Approximately 50% of patients have elevated serum levels of IgA. In more advanced cases there may be crescents, glomerular scarring, and tubular atrophy.
e. Management. Treatment is supportive and includes regular follow-up for the development of hypertension. Hypertension may eventually worsen proteinuria and renal function. Medications (angiotensin-converting enzyme [ACE] inhibitors, steroids, and immunosuppressants such as mycophenolate mofetil) are usually recommended for patients with associated pathologic proteinuria, renal insufficiency, or more significant glomerular inflammation on renal biopsy.
f. Prognosis is variable. Twenty to forty percent of patients eventually develop end-

stage renal disease (ESRD).
3. Henoch–Schönlein purpura (HSP) nephritis (see Chapter 16, section I)
a. Definition. HSP is an IgA-mediated vasculitis characterized by nonthrombocytopenic “palpable purpura” on the buttocks, thighs, and lower arms, in addition to abdominal pain, arthritis or arthralgias, and gross or microscopic hematuria.
b. Clinical features. Clinical findings related to renal involvement include the following:
1. In the majority of patients, the renal features of HSP are self-limited with complete recovery within 3 months. One to five percent of patients develop chronic renal failure.
2. If proteinuria and marked hematuria are present, there may be severe glomerular inflammation. Renal biopsy is indicated for significant proteinuria or if there is an elevated serum creatinine.
3. The renal biopsy in HSP nephritis is indistinguishable from that of a patient with IgA nephropathy.
4. Membranoproliferative glomerulonephritis (MPGN)
a. Definition. MPGN is a term used for three forms of histologically distinct glomerulonephritis that share similar features. MPGN is characterized by lobular mesangial hypercellularity and thickening of the glomerular basement membrane.
b. Clinical features
1. Patients typically present with acute nephritic syndrome or with nephrotic syndrome accompanied by microscopic or gross hematuria.
2. Hypertension is common.
3. Seventy-five percent of patients have low serum complement levels.
4. Clinical course is variable, although most patients ultimately develop ESRD.
c. Management. There is no standardized treatment for MPGN, although some patients may respond to corticosteroids or mycophenolate mofetil. ACE inhibitors may slow disease progression.
5. Membranous nephropathy (MN) is a rare form of glomerulonephritis in young children, although it may be seen in children and adolescents. MN presents with heavy proteinuria and may progress to renal insufficiency. MN is the most common cause of nephrotic syndrome in adults in the United States. It is an autoimmune disease sometimes associated with hepatitis B infections and SLE.
6. SLE nephritis (see Chapter 16, section IV.D.8)

VI. Nephrotic Syndrome (NS)
A. Definition. NS is a condition characterized by heavy proteinuria (>50 mg/kg/24 hours or by a urine total protein/creatinine ratio >3.5), hypoalbuminemia, hypercholesterolemia, and edema.
B. Epidemiology
1. Two-thirds of cases in children present before 5 years of age.
2. In young children, the ratio of boys to girls is 2:1. By late adolescence, both sexes are equally affected.
C. Classification. There are three categories of NS:
1. Primary NS, which refers to cases that are not a consequence of systemic disease. Primary NS accounts for 90% of all childhood cases of NS. The most common cause of primary NS in children is minimal change disease (MCD), which accounts for 95% of NS cases among young children and 50% of cases in older children and adolescents.
2. NS that results from other primary glomerular diseases, including focal segmental glomerulosclerosis (FSGS), MPGN, IgA nephropathy, and PSGN
3. NS that results from systemic diseases, including SLE and HSP
D. Pathophysiology
1. The basic physiologic defect is a loss of the normal charge- and size-selective glomerular barrier to the filtration of plasma proteins.
2. Excessive urinary protein losses lead to the hypoproteinemia of NS.
3. Hypercholesterolemia is a consequence of the hypoproteinemia.
a. Reduced plasma oncotic pressure induces increased hepatic production of plasma proteins, including lipoproteins.
b. Plasma lipid clearance is reduced because of reduced activity of lipoprotein lipase in adipose tissue.
E. Clinical features
1. Most children present with edema, which can range from mild periorbital edema to scrotal or labial edema to widespread edema. The edema often follows an upper respiratory infection (URI). Pleural effusions and hypotension may also occur.
2. Patients may rarely be asymptomatic at the time of diagnosis. In these patients, NS is diagnosed during an evaluation for asymptomatic proteinuria, and they are less likely to have MCD.
3. Patients are predisposed to thrombosis secondary to hypercoagulability. Rarely, patients may present with stroke or other thrombotic events such as renal vein thrombosis, deep vein thrombosis, and sagittal sinus thrombosis.
4. Patients are also at an increased risk for infection with encapsulated organisms, such as Streptococcus pneumoniae, and therefore may present with spontaneous bacterial peritonitis, pneumonia, or overwhelming sepsis.
5. The clinical course for the child with MCD follows periods of relapses and remissions. About one-third of patients have only one episode, one-third have infrequent relapses, and one-third will have frequent relapses. For the latter two groups, the nephrotic syndrome is a chronic illness in which the side effects of medications have to be weighed against the complications of the disease.
6. Many, but not all, children with MCD achieve a sustained remission by adolescence.
F. Diagnosis. Diagnosis is on the basis of clinical features and on the following studies:
1. Urinalysis typically reveals 3+ to 4+ protein, sometimes microscopic hematuria, and a very elevated urinary TP/CR. The presence of RBC casts indicates a cause other than MCD.
2. CBC may show an elevated hematocrit as a result of hemoconcentration resulting from

the hypoproteinemia. The platelet count may also be elevated.
3. Routine chemistries (electrolytes) may demonstrate metabolic acidosis, which may be caused by acquired renal tubular acidosis (in severe cases the heavy proteinuria of nephrotic syndrome may cause RTA). Hypoalbuminemia and elevated serum cholesterol are present. BUN and creatinine should be measured to assess for renal impairment.
4. C3, ANA, and antistreptococcal antibodies are indicated during an initial evaluation to rule out causes of NS other than MCD.
5. Renal ultrasound often shows enlarged kidneys.
6. Renal biopsy is rarely indicated in the young child with typical NS, unless the creatinine clearance is impaired or initial management with corticosteroids is ineffective.
7. Genetic testing for mutations associated with nephrotic syndrome may be indicated in the child who presents with nephrotic syndrome before their first birthday and in the steroid-resistant child.
G. Management. Treatment is dictated by the underlying cause of the NS.
1. Most children are hospitalized for initial treatment, although a relatively asymptomatic child with a reliable caregiver can be followed carefully as an outpatient.
2. If the child has widespread edema, scrotal or labial edema, hypotension, or symptomatic pleural effusions, IV infusions of 25% albumin should be given initially to achieve a diuresis and to maintain the intravascular volume.
3. The diet should consist of meals with no added salt.
4. Most patients with MCD respond to therapy with corticosteroids. Steroid-dependent and frequently relapsing children may achieve a prolonged remission during treatment with cyclophosphamide, mycophenolate mofetil, tacrolimus, or cyclosporine. For the steroid-resistant patient a prolonged course of tacrolimus plus steroids may induce a remission.
5. Because of the risk of pneumococcal infection, if the child is febrile, evaluation should include blood culture, urine culture, and chest radiograph. If peritonitis is suspected, paracentesis for Gram stain, culture, and cell count of the ascites fluid is indicated. Empiric broad-spectrum IV antibiotic coverage should be initiated.
H. Prognosis varies according to the underlying cause. Mortality approaches 5%, almost exclusively in children who are steroid-resistant and almost always from overwhelming infection or thrombosis.

VII. Hemolytic Uremic Syndrome (HUS)
See Chapter 13, section I.F.2.b.(3) and Chapter 7, Table 7-6.

A. Definition. HUS is a condition characterized by acute kidney injury (AKI) in the presence of microangiopathic hemolytic anemia and thrombocytopenia.
B. Subtypes. There are three different subtypes of HUS, which differ in their known etiology, treatments, and prognoses: Shiga-like toxin HUS, pneumococcal HUS, and atypical HUS.
C. Shiga-like toxin–associated HUS (STEC-HUS)
1. Epidemiology. STEC-HUS is the most common subtype seen in childhood.
2. Etiology
a. STEC-HUS occurs as a result of an intestinal infection with a toxin-producing bacterial strain. In North America, the most common pathogen is Escherichia coli 0157:H7. Other pathogens include other strains of E. coli and Shigella dysenteriae type
1. Testing the stool with cultures for enteropathogenic E. coli and for Shiga toxin is informative.
b. Known sources of bacterial contamination include undercooked beef, unpasteurized milk, produce, and contaminated fruit juices. Human-to-human transmission has been described.
3. Pathogenesis
a. Vascular endothelial injury by the Shiga-like toxin is the key to the pathogenesis of injury in STEC-HUS.
b. The toxin binds to endothelial cells, causing endothelial cell injury, most especially in the renal vasculature. This leads to platelet thrombi formation and renal ischemia from the microthrombi.
4. Clinical features. The clinical presentation includes a diarrheal prodrome (often bloody and may be severe) followed by the sudden onset of hemolytic anemia, thrombocytopenia, and AKI.
5. Management. Treatment is supportive.
a. Transfusions as needed for severe anemia and thrombocytopenia.
b. AKI is managed as described in section X.E.
c. The use of antibiotics is controversial in treating diarrhea due to HUS-associated bacteria. Although antibiotic treatment of E. coli hemorrhagic colitis with certain antibiotics may increase the likelihood that the patient will eventually develop HUS, there is some preliminary evidence that fosfomycin may be protective and could be considered during outbreaks of E. coli–associated diarrhea.
6. Prognosis. The prognosis is generally favorable and depends on the severity of the presentation.
a. Poor prognostic signs for renal recovery include a high white blood cell (WBC) count on admission and prolonged oliguria.
b. A minority of patients die during the acute phase from the complications of colitis, such as toxic megacolon, or from central nervous system complications, such as cerebral infarctions.
D. Pneumococcal HUS
1. Pneumococcal HUS is triggered by infection with pneumococcus and accounts for about 5% of the cases of HUS.
2. It is mediated by neuraminidase, which functions as a toxin in the presence of a S. pneumoniae infection. Plasma infusions may worsen the symptoms in this type of HUS, and if plasma exchange is considered, albumin should be used instead of plasma.
3. It often carries a worse prognosis than STEC-HUS because of necrotizing pneumonia.

E. Atypical HUS (aHUS)
1. Epidemiology. aHUS is much less common than STEC-HUS.
2. Etiology
a. Drugs (e.g., oral contraceptives, cyclosporine, tacrolimus) or pregnancy may cause aHUS.
b. Inherited aHUS occurs with both autosomal dominant and autosomal recessive inheritance patterns, although not all patients have identifiable mutations. These genetic mutations cause chronic, excessive activation of complement, which also leads to platelet activation, endothelial cell damage, and systemic thrombotic microangiopathy.
3. Clinical features. Clinical findings are similar to those of STEC-HUS. Diarrhea may also be present, and severe proteinuria and hypertension are more consistently found. The clinical course is generally more severe with multiorgan damage.
4. Management. Treatment is supportive. Inciting medications, if any, must be stopped immediately.
5. Prognosis. Some patients have a chronic relapsing course (recurrent HUS). All patients with aHUS have a higher risk of progression to ESRD than patients with STEC-HUS.

VIII. Hereditary Renal Diseases
A. General concepts. Because many inherited renal diseases present in childhood, a careful family history is critical in all children with renal disease.
B. Alport syndrome
1. Definition. Alport syndrome is a form of progressive hereditary nephritis that is secondary to defects in the side chains of type IV collagen within the glomerular basement membrane.
2. Etiology. Inheritance is usually X-linked dominant, although autosomal dominant and autosomal recessive variants exist.
3. Clinical features
a. Renal manifestations initially include hematuria, often gross hematuria, and sometimes hypertension. ESRD often occurs in males with X-linked Alport syndrome as early as adolescence, but the age of onset of ESRD differs between kindreds. Women who carry the gene are less likely to develop ESRD, but it may occur. Autosomal dominant and autosomal recessive Alport syndrome may also lead to ESRD.
b. Hearing loss typically begins in childhood and progresses; approximately 50% of adults have some loss of hearing, ranging from mild to severe.
c. Ocular abnormalities involving the lens and retina occur in 25–40% of patients.
4. Management. Therapy includes treatment of hypertension, use of ACE inhibitors (even in patients who have proteinuria without hypertension), sometimes with the addition of an angiotensin receptor blocker to slow the progression of renal disease, and eventually renal transplantation.
C. Multicystic renal dysplasia. This condition is the most common cause of a renal mass in the newborn, occurring in 1 in 4300 live births, and is most often unilateral. The inheritance is not clear, but it appears to be a sporadic occurrence. See section XII.D.2 for more details.
D. Autosomal recessive polycystic kidney disease (ARPKD) or infantile polycystic kidney disease
1. Epidemiology. ARPKD is uncommon, occurring in approximately 1 in 10,000–40,000 live births.
2. Clinical features
a. The most severely affected infants have a maternal history of oligohydramnios secondary to nonfunctioning or poorly functioning kidneys in utero. This leads to pulmonary hypoplasia, which may be incompatible with life.
b. Greatly enlarged cystic kidneys
c. Severe hypertension is common.
d. Liver involvement of variable clinical severity is a constant finding, including cirrhosis with portal hypertension.
3. Prognosis. Although the degree of renal insufficiency in infancy may range from mild to severe, ARPKD is progressive and ultimately all patients require renal transplantation.
E. Autosomal dominant polycystic kidney disease (ADPKD) or adult polycystic kidney disease
1. Epidemiology. ADPKD is a common genetic disorder (affecting about 1 in 500 individuals) that usually presents in adulthood (20–40 years of age). There are two gene mutations that cause ADPKD; ADPKD1 mutations are more common and cause an earlier onset of disease than ADPKD2 mutations.
2. Clinical features. Clinical findings are variable and include abdominal pain, flank masses, urinary tract infection (UTI), gross or microscopic hematuria, hypertension, or

renal insufficiency. Associated cerebral aneurysms may occur, with early death.
3. Prognosis. Most patients develop severe hypertension and renal insufficiency, eventually requiring transplantation.
F. Medullary sponge kidney. This condition occurs sporadically or may have autosomal dominant inheritance. Patients may be asymptomatic or have hematuria, UTI, or nephrolithiasis.
G. Nephronophthisis. This is a ciliopathy that occurs in several forms. The infantile, juvenile, and adolescent forms are autosomal recessive and lead to ESRD in childhood or young adulthood, and there are often significant associated extrarenal manifestations in 10–15% of patients, including retinal degeneration, cerebellar vermis hypoplasia, occipital encephalocele, hepatic fibrosis, situs inversus, bronchiectasis, and skeletal defects. More than 13 mutated genes have been described that lead to nephronophthisis.

IX. Renal Tubular Acidosis (RTA)
A. Definition. RTA refers to a group of congenital or acquired disorders that result from the inability of the kidney to maintain normal acid–base balance because of defects in bicarbonate conservation or because of defects in the excretion of hydrogen ions.
B. Etiology (Table 11-2)
1. Congenital forms of RTA are caused by mutations in various transporters in the proximal or distal tubular cells.
2. Acquired forms of RTA may be caused by nephrotoxic drugs (e.g., amphotericin) or systemic diseases (e.g., autoimmune disorders).
C. Clinical features (Table 11-2). Symptoms vary with the type of RTA and with the patient’s
age.
1. Infants and young children tend to present with growth failure and vomiting, and, at times with life-threatening metabolic acidosis.
2. Older children and adults may have recurrent calculi, muscle weakness, bone pain, and myalgias.
3. Some forms of RTA result in nephrocalcinosis, which in turn may lead to polyuria from urinary concentrating defects.
4. The classic electrolyte presentation is a hyperchloremic metabolic acidosis with a
normal serum anion gap.
D. Types of RTA (Table 11-2)
E. Evaluation. RTA should be considered in patients who present with a non–anion gap hyperchloremic metabolic acidosis. Acidosis should be confirmed by a venous blood gas.
1. Initial laboratory studies should include serum potassium, phosphorus and uric acid, urine pH, and urinalysis to evaluate for proteinuria and glucosuria. Calculation of the urine anion gap (urine Na+ + urine K+ − urine chloride) is important; a positive urine anion gap is seen in Types I and IV RTA and may be seen in Type II RTA.
2. If there are signs of a diffuse tubular disorder (manifested by hypokalemia, hypophosphatemia, and aminoaciduria), the patient should be evaluated for Fanconi syndrome by performing more extensive testing of other tubular functions.

Table 11-2
Types of Renal Tubular Acidosis (RTA)

Type of
RTA Characteristic Features Causes or Associations Clinical Presentation Treatment
Distal RTA
(Type I)
Inability of the distal renal tubular cells to excrete acid (H+)
Isolated inherited defect Associated with nephrotic syndrome, sickle cell anemia, connective tissue disorders
Associated with toxins, drugs (amphotericin)
Vomiting Growth failure Acidosis Nephrocalcinosis
and nephrolithiasis
Small doses of oral alkali
Proximal RTA
(Type II)
Impaired bicarbonate reabsorption by the proximal renal tubular cells
Isolated inherited defect Intoxication (heavy metals)
Prematurity
Drugs (gentamicin) Associated with more global defects in tubular reabsorption (Fanconi syndrome*)

Vomiting Growth failure Acidosis
Muscle weakness
Large doses of oral alkali

Type IV
RTA
Transient acidosis in
Associated with renal
Patients may be
Furosemide
infants and children disorders such as asymptomatic or to lower
Hyperkalemia is the obstructive uropathy and may present with serum
hallmark interstitial nephritis failure to thrive potassium;
Diabetes mellitus oral alkali
Associated with
mineralocorticoid
deficiency states
*Findings associated with Fanconi syndrome: proximal RTA, hyperphosphaturia, aminoaciduria, glucosuria, and potassium wasting.

X. Acute Kidney Injury
A. Definition. AKI is defined as an abrupt decrease in the ability to excrete nitrogenous wastes.
B. Etiology (Table 11-3)
C. Clinical features
1. Systemic signs and symptoms depend on the cause and severity of the renal insult but often include lethargy, nausea, vomiting, respiratory distress, hypertension, and sometimes seizures.
2. The clinical presentation may be oliguric (diminished urine output) or nonoliguric (normal urine output). In children, oliguria is defined as a urine output < 1 mL/kg/hour.
D. Evaluation
1. Laboratory tests should include serum electrolytes, BUN, creatinine, urinalysis, and urinary protein and creatinine levels, as well as a more specific investigation for the cause of kidney injury, such as testing for ANCA or drug levels of nephrotoxic medications based on the clinical history.
2. Imaging studies may include a renal or pelvic ultrasound and a nuclear renal scan to evaluate renal function.
E. Management
1. If possible, the specific cause should be addressed (e.g., removal of a nephrotoxic drug).
2. If the patient is intravascularly volume depleted, the intravascular volume should be restored first with appropriate IV fluids, and then total fluid intake should be restricted to the patient’s insensible losses (approximately 300 mL/m2/day) plus output (urine, stool) replacement.
3. Electrolyte intake should be matched to estimated electrolyte losses. Typically, sodium, potassium, and phosphorus intake are restricted.
4. Protein intake should be restricted to the recommended dietary allowance (RDA) of protein for age. Caloric intake should also be at the RDA for age.
5. Patient monitoring should include daily weights, frequent blood pressure measurements, calculation of intake and output, and monitoring of electrolytes.
6. Dialysis therapy (peritoneal dialysis, hemodialysis, or continuous renal replacement therapy) is used when conservative management fails to maintain the patient in safe biochemical, nutritional, and fluid balance.

Table 11-3
Etiologies of Acute Kidney Injury (AKI)

Categories of AKI Causes of Renal Failure Specific Examples Laboratory
Findings
Prerenal Caused by a reversible ↓ in renal
perfusion that leads to a ↓ in GFR Dehydration ↑ BUN/Creat
ratio > 20
Hemorrhage ↑ Urine SG ≥ 1.030
Congestive heart failure Urine osmolality > 500
Septic shock Urine Na+ < 20
Hypoproteinemic states *FeNa < 1% in older children, <2.5% in neonates
Renal parenchymal Damage to glomerulusDamage to tubules (acute tubular necrosis)Damage to interstitium
(acute interstitial nephritis) PSGN Hematuria
Lupus nephritis Proteinuria↑ Urinary β2- microglobulin
HUS

hypoperfusionDrugs (semisynthetic penicillins) neonates
Eosinophilia, eosinophiluria
Postrenal Obstruction of urine flow from either a solitary kidney, from both kidneys, or from the urethra Stones Dilation of renal collecting system on renal
ultrasound
Tumor
Ureterocele
Urethral trauma
Neurogenic bladder
Posterior urethral valves in males
Vascular ↓ Perfusion of the kidneys Renal artery embolus (especially in the presence of an umbilical artery
catheter) ↓ Renal blood flow on nuclear renal scan
Renal vein thrombosis, presenting with sudden-onset gross hematuria and a unilateral or bilateral flank mass, with ↑ incidence in
infants of diabetic mothers
*

HUS = hemolytic uremic syndrome; PSGN = poststreptococcal glomerulonephritis; FeNa = fractional excretion of sodium;
SG = specific gravity; GFR = glomerular filtration rate; Creat = creatinine; BUN = blood urea nitrogen.

XI. Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD)
A. Etiology
1. The most common causes include glomerular diseases (e.g., FSGS), congenital or inherited kidney diseases (e.g., renal dysplasias or obstructive uropathies), reflux nephropathy, collagen vascular diseases, cystic kidney diseases, interstitial nephritis, and HUS.
2. The cause is unknown in up to 10% of cases.
3. Determining the cause of the child’s chronic kidney disease may have implications for the child and his or her family, especially important in cases of inherited disorders. Specific therapies may modify disease progression, some genetic diseases may occur in siblings or offspring, and some diseases may recur in transplanted kidneys.
B. Clinical features. Clinical findings may include short stature, anemia, failure to thrive, polyuria and polydipsia, lethargy, and rickets.
C. Evaluation
1. Investigation for the causes of CKD
2. Careful family history
3. Assessment of growth and nutrition
4. Evaluation for renal osteodystrophy (i.e., bone disease secondary to renal failure)
5. Serologic testing for collagen vascular diseases
6. Renal imaging to look for structural kidney abnormalities
7. Renal biopsy (in some cases)
D. Management
1. Medical
a. Nutritional management includes assurance of adequate caloric intake and avoidance of high phosphorus, high sodium, and high potassium foods. Patients are also given oral phosphate binders and vitamin D analogues to prevent renal osteodystrophy. Protein intake should be at the RDA for age.
b. Biochemical management includes monitoring and management of serum electrolytes, BUN, creatinine, calcium, and alkaline phosphatase.
c. Blood pressure monitoring and management are critical.
d. Anemia is treated with iron and recombinant erythropoietin therapy.
e. Growth is closely monitored, and patients may require recombinant human growth hormone if their growth fails to normalize with other medical interventions.
2. Dialysis is initiated or transplantation is considered when the glomerular filtration rate is <10% of normal, or earlier if the child is symptomatic.
a. Peritoneal dialysis is generally the preferred dialysis modality in infants and children.
b. Chronic hemodialysis may also be performed in children and requires vascular access via an indwelling catheter or an arteriovenous fistula. This is technically very difficult in an infant.
c. Kidney transplantation is the preferred treatment for children with ESRD.
1. Living related donors and living unrelated donors are preferred over deceased donors because of better kidney transplant outcomes. Graft outcome varies with donor source. Approximately 80% of living donor kidneys and 65% of deceased donor kidneys remain functioning 5 years after transplant.
2. Kidney transplantation requires lifelong immunosuppression with increased risks of infection and subsequent malignancies.

3. The most common causes of transplant loss include acute and chronic rejection, noncompliance with medications, technical problems during surgery, and recurrent disease.

XII. Structural and Urologic Abnormalities
A. Structural and urologic abnormalities are common, occurring in 6–10% of children.
B. Congenital obstructive abnormalities may occur at any level in the urinary tract. Bilateral lesions threaten renal function.
1. Ureteropelvic junction obstruction may occur as a result of kinks, fibrous bands, or overlying aberrant blood vessels.
2. Ureterovesical junction obstruction may occur as a result of ureterocele, primary megaureter, or abnormal insertion of the ureter into the bladder.
3. Bladder outlet obstruction may occur as a result of posterior urethral valves in males, may be secondary to polyps or tumors, and may be associated with prune belly syndrome (i.e., absence of rectus muscles, bladder outlet obstruction, and, in males, cryptorchidism). Bladder outlet obstruction is typically associated with impairment in renal function.
4. Any form of congenital obstruction, if severe in utero, may lead to abnormal renal development (renal dysplasia). Severe impairment of renal function from any in utero cause may lead to oligohydramnios, which results in pulmonary hypoplasia that may be incompatible with life.
C. Acquired obstruction may occur as the result of renal calculi [see section XIII], tumors, or strictures.
D. Renal abnormalities
1. Renal agenesis occurs as a result of the failure of development of the mesonephric duct or the metanephric blastema, and may be associated with severe congenital anomalies in other organ systems (e.g., heart and hearing).
a. Unilateral renal agenesis occurs in 0.1–0.2% of children.
b. Bilateral renal agenesis is very rare. Infants die in the perinatal period secondary to associated pulmonary hypoplasia.
2. Renal dysplasia is much more common than renal agenesis.
a. Pathologically, renal dysplasia is associated with altered structural organization of the kidney, ranging in severity from mild to severe.
b. Functionally, renal dysplasia is associated with concentrating defects, RTA, and varying degrees of decreased kidney function.
c. Patients with relatively mild renal dysplasia and its associated renal functional abnormalities at birth may experience improved kidney function in later infancy and childhood, only to deteriorate in late childhood or adolescence.
d. Severe renal dysplasia results in a nonfunctional kidney.
1. The most common abdominal mass discovered in newborns is the multicystic dysplastic kidney, which is usually associated with an atretic ureter.
2. If bilateral and severe, multicystic dysplastic kidneys are incompatible with life. These infants are usually born with the stigmata of Potter syndrome (see Chapter 5, section IV.I.6).
3. Other structural abnormalities include horseshoe kidney (fusion of the lower poles of the kidneys), renal ectopia (kidney located outside of the renal fossa, such as in the pelvis), and duplication anomalies.
E. Vesicoureteral reflux (VUR)
1. Definition. VUR is defined as urine refluxing from the urinary bladder into the ureters and the renal collecting system.
2. Epidemiology. It is estimated that at least 0.5% of healthy infants have some degree of

VUR.
3. Etiology
a. VUR is caused by abnormalities of the ureterovesical junction, most commonly a short submucosal tunnel in which the ureter inserts through the bladder wall. It also is associated with dysfunctional voiding patterns in infants and children.
b. VUR has been described to have multiple inheritance patterns, including autosomal dominant inheritance with variable expression, autosomal recessive, or X-linked inheritance.
4. Classification. VUR is graded from grade 1 to grade 5 (Figure 11-4).
5. Clinical features
a. Most children with lower grades of VUR eventually have spontaneous resolution of the reflux.
b. VUR may predispose to episodes of pyelonephritis, and severe pyelonephritis in turn may lead to renal scarring, especially in infants and young children.
c. Severe in utero VUR may lead to renal hypoplasia/dysplasia and compromised kidney function.
d. Reflux nephropathy is the pathologic entity resulting from severe VUR. Kidneys show segmental scars, contraction, and interstitial nephritis, and this may lead to ESRD and hypertension.
6. Diagnosis. VUR is diagnosed by voiding cystourethrogram (VCUG) in which contrast is introduced into the urinary bladder via a urinary catheter. The bladder and kidneys are imaged under fluoroscopy during filling of the bladder and during voiding.
7. Management
a. Low-dose prophylactic antibiotics were previously routinely prescribed to reduce the incidence of UTI until the child outgrew the VUR. However, more recent studies have suggested that the benefits of prophylactic antibiotics may not outweigh the risks, especially in older children with low-grade VUR. The infant with high-grade VUR (e.g., grades 4 or 5) and a history of febrile UTI is still a candidate for prophylactic antibiotic therapy and close follow-up.
b. Children with grade 4 or 5 reflux should be referred to a pediatric urologist for consideration of surgical reimplantation of the ureters.

FIGURE 11-4 Classification of vesicoureteral reflux.

XIII. Urolithiasis
A. Epidemiology. Renal stones are uncommon in children, and predisposing metabolic disorders should be sought in any child presenting with urinary calculi. There is a higher incidence in overweight and obese children.
B. Etiology. The most common stones seen in childhood include stones of calcium salts, uric acid, cysteine, or magnesium ammonium phosphate (struvite). Conditions associated with urolithiasis that should be considered include the following:
1. Hypercalciuria, which predisposes to calcium-containing stones. Hypercalciuria may be idiopathic or caused by hypercalcemia, familial hypercalciuria, or furosemide use (especially in premature infants).
2. Hypocitraturia, which predisposes to calcium-containing stones and is an inherited condition.
3. Hyperoxaluria, which may be inherited or secondary to malabsorption from the GI tract (e.g., inflammatory bowel disease)
4. Distal RTA
5. Hyperuricosuria, which may occur during the treatment of leukemia or lymphoma, with Lesch–Nyhan syndrome or with primary gout
6. Cystinuria, which is an autosomal recessive disorder that may lead to radiopaque renal stones
7. UTI, especially with Proteus mirabilis
8. Hyperparathyroidism
C. Clinical features. Clinical findings include flank or abdominal pain, gross or microscopic hematuria, or symptoms of cystitis or pyelonephritis.
D. Diagnosis and evaluation. Because of the possibility of an underlying metabolic disorder, children with urolithiasis should have a careful evaluation, including the following:
1. Laboratory testing should include electrolytes, BUN, creatinine, calcium, phosphorus, parathyroid hormone (PTH) level, uric acid level, and venous blood gas to rule out RTA.
2. Urine testing should include urinalysis with microscopy, urinary oxalate-to-creatinine ratio to identify hyperoxaluria, random first morning urine for calcium-to-creatinine ratio to identify hypercalciuria and uric acid-to-creatinine ratio to identify hyperuricosuria, urine culture, and testing for cystinuria. Twenty-four–hour urine collections are important to measure 24-hour urinary excretion of creatinine, oxalate, uric acid, citrate (low urinary citrate predisposes to stone formation), calcium, phosphorus, magnesium, and cysteine.
3. Imaging studies, including a plain radiograph of the abdomen and renal ultrasound, are necessary to confirm and identify the stone(s). Sometimes a high-resolution abdominal CT scan can identify the stone.
4. Stone fragment analysis, if a fragment is collected.
E. Management. Management is aimed first at hydration and the relief of any obstruction, treating any associated UTI, and then specific therapy on the basis of the underlying predisposing cause of the urolithiasis. On an on-going basis, patients should have, increased water intake at least to the maintenance fluid range, as well as reduced sodium intake. Patients with hypocitraturia can be treated with increased fluids that contain citrate.

XIV. Urinary Tract Infection (UTI)
A. Epidemiology. UTI is one of the most common bacterial infections in children.
1. Incidence of symptomatic UTI during infancy is 0.4–1%.
2. Until 6 months of age, UTIs are twice as common in infant boys than girls. After 6 months of age, UTIs are much more common in girls.
3. Before 6 months of age, UTIs are 10 times more common in uncircumcised boys as compared with boys who are circumcised.
B. Etiology. The vast majority of UTIs are caused by enteric bacteria, especially E. coli. Other pathogens include Klebsiella, Pseudomonas, Staphylococcus saprophyticus (especially in adolescent females), Serratia, Proteus (associated with a high urinary pH), and Enterococcus.
C. Pathogenesis
1. Most bacteria enter the urinary tract by ascending through the urethra.
2. Bacterial properties that promote the adherence of bacteria to the urothelium increase the likelihood of UTI (such as the presence of P fimbria on E. coli).
D. Clinical features. UTI symptoms vary with the age of the child.
1. In neonates, symptoms are nonspecific and include lethargy, fever or temperature instability, irritability, and jaundice.
2. In older infants, symptoms include fever, vomiting, and irritability. Pyelonephritis is difficult to diagnose in young nonverbal children but should be suspected if fever or systemic symptoms are present.
3. In young children who were previously toilet-trained or dry at night, UTI may present with nocturnal enuresis or daytime wetting.
4. In older children, cystitis (lower tract infection) is diagnosed when children present with only low-grade or no fever and with complaints of dysuria, urinary frequency, or urgency. Pyelonephritis (upper tract infection) is associated with back or flank pain, high fever, and other symptoms and systemic signs such as vomiting and dehydration.
E. Diagnosis and evaluation
1. Diagnosis depends on the proper collection of the urine specimen.
a. In neonates and infants, urine for culture must be collected by suprapubic aspiration of the urinary bladder or via a sterile urethral catheterization. A clean “bagged” urine sample is adequate for a screening urinalysis but not for culture.
b. In older children who can void on command, a careful “clean-catch” urine sample is adequate for culture.
c. Because bacteria multiply exponentially at room temperature, it is crucial that the urine be cultured immediately or at least refrigerated immediately until it can be cultured.
2. Urinalysis findings suggestive of UTI include the presence of leukocytes on microscopy (>5–10 WBCs/HPF) and a positive nitrite or leukocyte esterase on dipstick. Note however that not all bacteria produce nitrites (e.g., enterococcus), which may lead to a negative nitrite test.
3. Urine culture remains the “gold standard” for diagnosis. Significant colony counts
depend on the culture method:
a. Any growth on urine collected by suprapubic aspiration
b. ≥10,000 colonies in samples obtained by sterile urethral catheterization
c. ≥50,000–100,000 colonies of a single organism in urine collected by clean-catch technique
4. Imaging
a. Imaging is indicated in selected children with UTI, because children with UTI have

an increased incidence of structural abnormalities of the urinary tract (e.g., vesicoureteral reflux).
b. All children with pyelonephritis, all children with recurrent UTI, prepubertal males, and girls younger than 2 years of age with cystitis should have an imaging evaluation, which should include a renal ultrasound and consideration for a VCUG.
F. Management
1. Empiric antibiotic therapy should be started in symptomatic patients with a suspicious urinalysis while culture results are pending. Commonly used oral antibiotics include trimethoprim–sulfamethoxazole or cephalexin.
2. Neonates with UTIs are admitted to the hospital for initial IV management, which commonly includes ampicillin and gentamicin.
3. Toxic-appearing children with high fever and children with dehydration should also be admitted to the hospital for initial IV antibiotics and hydration. Patients can be transitioned to oral antibiotics once the child has shown clinical improvement and sensitivities are available.
4. Duration of treatment for cystitis is usually 7–10 days, and for pyelonephritis, 14 days.

Review Test
1. A 3-week-old uncircumcised male infant presents with a 2-day history of very poor feeding. He now takes only 1 oz of formula every 3 hours, instead of the usual 2–3 oz. The parents state that their son has become increasingly irritable, and they deny fever, vomiting, or other symptoms. You perform a laboratory evaluation to look for evidence of infection. A urinalysis demonstrates 25–50 white blood cells per high-power field. You suspect that the infant has a urinary tract infection (UTI). Which of the following statements regarding UTI in this infant is correct?
A. There would be no significant difference in his risk of UTI had he been circumcised.
B. During infancy, the risk of developing a UTI is the same as that of an infant girl.
C. A clean “bagged” urine sample is adequate for culture in this febrile infant with no obvious source of infection.
D. If diagnosed with a UTI, this infant has an increased risk of having vesicoureteral reflux as compared with an infant without a UTI.
E. This infant should be treated empirically with oral antibiotics on an outpatient basis and reevaluated within 24 hours.
2. A 5-year-old boy is brought to your office by his parents, who noticed that when their son urinated earlier in the day, his urine appeared red. Dysuria, urinary frequency, and fever are absent, and he is well appearing on examination. Which of the following statements regarding this patient’s presentation and subsequent workup is correct?
A. This patient may be diagnosed with microscopic hematuria if there are ≥10 red blood cells (RBCs) per high-power field on a single urine sample.
B. On urinalysis, RBCs that appear as biconcave disks indicate that they originated in the glomerulus, and this suggests that he has glomerulonephritis.
C. Because of his presentation with hematuria at a young age, this patient will likely have persistent microscopic hematuria.
D. This patient’s red-colored urine may have resulted from eating beets the previous day.
E. This patient’s urinary dipstick for blood may be falsely positive if he has recently ingested ascorbic acid (vitamin C).
3. A 4-year-old girl who recently returned from Southeast Asia presents with a history of watery diarrhea, vomiting, and decreased urine output. She is irritable and is crying, although she stops crying when held by her parents. Examination reveals tachycardia with a normal blood pressure, dry mucous membranes, and good peripheral perfusion with normal skin turgor. Which of the following statements regarding rehydration of this child is correct?
A. The goal of the emergency phase of intravenous rehydration is to restore or maintain intravascular volume to ensure perfusion of the vital organs. The type of intravenous fluids administered depends on the serum level of sodium in the blood.
B. Appropriate bolus fluids in the emergency phase of intravenous rehydration should include 20 mL/kg of one half–normal saline solution.
C. If this patient is isonatremic or hypernatremic, her fluid deficits should be replaced over 24 hours, but if she is hyponatremic, her fluid deficits should be replaced over 48 hours.
D. If stool losses continue, these losses should not be replaced until all the deficit fluids are replaced.
E. Oral rehydration therapy may be effective even if this child has a secretory diarrhea.
4. A 5-year-old boy has a 3-day history of headache, “puffiness,” and dark-colored urine. Physical examination reveals hypertension and periorbital and peripheral edema. Urinalysis reveals hematuria with red blood cell casts and 2+ proteinuria. The diagnosis of poststreptococcal glomerulonephritis is suspected pending further evaluation. Which of the

following statements regarding this patient’s diagnosis is correct?
A. If diagnosed with poststreptococcal glomerulonephritis, this patient would be expected to have mild to moderate impairment of renal function and normal serum complement levels.
B. This patient is likely to have had an infection of the skin or pharynx with a nephritogenic strain of group A β-hemolytic streptococcus 60–90 days before the current presentation.
C. A negative antistreptolysin O titer would rule out the diagnosis of poststreptococcal glomerulonephritis in this patient.
D. Antibiotic treatment with penicillin for streptococcal pharyngitis would have prevented this patient’s glomerulonephritis.
E. If the diagnosis of poststreptococcal glomerulonephritis is confirmed, the prognosis for this patient is excellent; complete recovery usually occurs.
5. A previously healthy 3-year-old girl presents with a 2-week history of progressive facial edema. You suspect nephrotic syndrome. Which of the following statements regarding this patient’s presentation, evaluation, and management is correct?
A. This patient’s nephrotic syndrome is most likely a consequence of a primary glomerular disease, such as IgA nephropathy.
B. This patient’s age of presentation is atypical; the peak age of presentation of nephrotic syndrome is between the ages 5 and 15 years.
C. This patient should undergo renal biopsy to confirm the diagnosis and to establish an appropriate approach to management.
D. If this patient develops a high fever, she should be empirically treated with antibiotics to cover possible pneumococcal peritonitis.
E. Discovery of heavy proteinuria, hypoalbuminemia, and hypocholesterolemia on laboratory testing would confirm the diagnosis.
6. A previously healthy 3-year-old boy presents with lethargy, pallor, and bloody diarrhea. He has had bloody stools for 4 days, and in the past 2 days he has developed fatigue and pale skin. He is drinking less than normal, and his urine output is somewhat decreased. The parents deny any travel or medication use. Physical examination reveals mild hypertension, pale mucous membranes, abdominal tenderness, and a petechial skin rash on the trunk and extremities. Hemolytic uremic syndrome (HUS) is suspected. Which of the following statements regarding the suspected diagnosis is correct?
A. Given the nature of this patient’s symptoms and his young age, he is most likely to have atypical HUS.
B. Parenteral antibiotic treatment with gentamicin is indicated for the treatment of suspected Escherichia coli hemorrhagic colitis.
C. Although he has a petechial rash, his platelet count will be normal.
D. The prognosis is poor; he will likely have a chronic relapsing course, with a high chance of end-stage renal disease.
E. The renal impairment is caused by toxin binding to renal vascular endothelial cells.
7. A 14-year-old Japanese American boy has 3+ protein and 4+ blood with red blood cell casts on a routine screening urinalysis conducted as part of a health maintenance evaluation. Further questioning reveals two prior episodes of “brown-colored urine” concurrent with upper respiratory tract infections during the last 3 years. Which of the following is the most likely diagnosis?
A. Membranous nephropathy
B. Systemic lupus erythematosus nephritis
C. IgA nephropathy
D. Membranoproliferative glomerulonephritis
E. Henoch–Schönlein purpura nephritis

8. A 3-year-old girl has a 2-day history of fever, irritability, and emesis. Urine culture grows
>100,000 colonies/mL of Escherichia coli. She is treated with cephalexin and returns 10 days later for an imaging evaluation to rule out a structural abnormality of the urinary tract. A voiding cystourethrogram reveals grade 2 vesicoureteral reflex (VUR), but her renal ultrasound is normal. Which of the following statements regarding VUR is correct?
A. Inheritance of VUR is most likely to be autosomal recessive.
B. The chance of developing chronic renal insufficiency as a result of VUR is 50%.
C. Referral to a pediatric urologist for ureteral reimplantation is appropriate.
D. The VUR is likely caused by a short submucosal tunnel in which the ureter inserts through the bladder wall.
E. Because this patient has grade 2 VUR, she should be placed on prophylactic antibiotics.
9. A 1-year-old boy has a 2-day history of irritability, decreased oral intake, decreased urine output, occasional watery diarrhea, and tactile fever. On physical examination, he is nontoxic and moderately dehydrated and has a temperature of 38.3°C (101°F). You admit him for intravenous rehydration because of his dehydration. Which of the following statements regarding his maintenance fluid and electrolyte requirements is correct?
A. His maintenance sodium requirement is approximately 1 mEq/kg/day.
B. His maintenance water requirement is 1000 mL/m2/day of body surface area.
C. His fever will result in increased insensible losses, and maintenance fluids should therefore be increased by 5% for every degree of temperature above 38°C.
D. His maintenance fluid calculations need to be adjusted for increased ongoing losses should he develop protracted vomiting or profuse watery diarrhea.
E. Maintenance fluid calculations for this child take into account both sensible and insensible losses.
10. A 4-day-old male infant has gross hematuria. His parents noticed the bleeding today when they changed his diaper. Perinatal history is remarkable for a term gestation complicated by gestational diabetes mellitus. Physical examination reveals hypertension and a right-sided flank mass. In addition, the infant appears very sleepy, and his mucous membranes are dry. Which of the following is the most likely explanation for his hematuria?
A. Maternal systemic lupus erythematosus nephritis
B. Adenovirus infection
C. Sickle cell disease
D. Hypercalciuria
E. Renal vein thrombosis
11. A 6-month-old female infant with a 2-week history of vomiting is brought to your office by her parents. The vomiting occurs three to four times per day, and her parents report she has been very fussy. Review of her growth records reveals very poor growth consistent with failure to thrive. A complete blood count is normal, but an electrolyte panel shows metabolic acidosis. Which of the following laboratory findings would be most consistent with suspected renal tubular acidosis?
A. Hypokalemia
B. Hyperphosphatemia
C. Hyperchloremia
D. Elevated serum anion gap
E. Hypocalcemia

The response options for statements 12–14 are the same. You will be required to select one answer for each statement in the following set.

A. Autosomal dominant
B. Autosomal recessive

C. Sporadic
D. X-linked

For each patient, select the likely mode of inheritance of the disease.

1. A 6-month-old girl with bilateral abdominal masses and severe hypertension, whose older sister died as a neonate after being diagnosed with oligohydramnios.
2. A 12-year-old boy who has three renal cysts on a renal ultrasound that was performed for the evaluation of microscopic hematuria. The patient’s paternal grandfather died of a stroke at 32 years of age, and the patient’s father has hypertension.
3. A 15-year-old boy who has mild hearing loss, mild hypertension, hematuria, and proteinuria.

Answers and Explanations
1. The answer is D [XIV.A, XIV.E.1, and XIV.F]. Infants with urinary tract infections (UTIs) have an increased risk of having underlying structural abnormalities, including vesicoureteral reflux. A structural abnormality of the urinary tract, such as vesicoureteral reflux, predisposes a child to developing a UTI. Before 6 months of age, UTIs are twice as common in boys, but after 6 months of age, UTIs are more common in girls. Before 6 months of age, UTIs are 10 times more common in uncircumcised boys as compared with circumcised boys. In neonates and infants, urine for culture must be collected by suprapubic aspiration of the urinary bladder or by a sterile urethral catheterization. Bagged specimens obtained from an infant are inappropriate for culture as they are very likely to be contaminated. Outpatient management for older nontoxic children with suspected UTI may be appropriate. However, toxic-appearing children, neonates, and patients who have significant dehydration should be hospitalized and administered intravenous antibiotics initially.
2. The answer is D [Figure 11-1]. Patients may develop red-colored urine from the ingestion of exogenous pigments, such as those found in beets, and from medications, such as phenytoin and rifampin. Such patients have negative urine dipsticks for blood. Although 4–5% of school children may have microscopic hematuria on a single voided urine sample, only 0.5–2% have persistent microscopic hematuria on retesting. The diagnosis of microscopic hematuria may be made if ≥6 red blood cells (RBCs) are noted per high-power field on three or more consecutive urine samples. Patients with positive dipsticks for blood should have microscopic evaluations of fresh urine specimens. RBCs that appear as normal biconcave disks usually originate in the lower urinary tract, unlike dysmorphic RBCs, which are more likely to originate in the glomerulus. False-negative results on dipstick for blood may occur with ascorbic acid (vitamin
C) ingestion.
3. The answer is E [I.D, I.E]. Oral rehydration therapy has been shown to be a safe and inexpensive alternative to intravenous rehydration and effective even in the face of secretory diarrhea, such as would be seen in cholera. Patients with secretory diarrhea still maintain their ability to absorb fluid and electrolytes through an intact, coupled cotransport mechanism. However, oral rehydration therapy should not be used for patients with severe life- threatening dehydration, paralytic ileus, or gastrointestinal obstruction. In patients with these problems, parenteral rehydration is more appropriate. The goal of the first phase of parenteral rehydration (emergency phase) is to restore or maintain the intravascular volume to ensure perfusion of vital organs, and this phase is the same for all patients (regardless of the patient’s initial serum sodium level). Appropriate fluids for use in the emergency phase include isotonic crystalloids, such as normal saline or lactated Ringer solutions in boluses of 20 mL/kg. One quarter– or one half–normal saline is not an appropriate intravenous fluid for the emergency phase. The subsequent repletion phase, or the more gradual correction of fluid and electrolyte deficits, should occur over 24 hours for patients with isonatremic and hyponatremic dehydration, and over 48 hours for patients with hypernatremic dehydration. There is a risk of cerebral edema if deficit replacement occurs too quickly in patients with hypernatremic dehydration. Ongoing losses should be replaced on a “milliliter for milliliter basis” concurrent with the replacement of deficits.
4. The answer is E [V.F.1]. The most common form of acute glomerulonephritis in school-age children is poststreptococcal glomerulonephritis. Patients usually present with hematuria, proteinuria, and hypertension after an infection of the skin (sometimes up to 28 days after impetigo) or pharynx (usually 10–14 days after pharyngitis) with a nephritogenic strain of group A β-hemolytic streptococcus. The prognosis for children with poststreptococcal glomerulonephritis is excellent, and affected children usually recover completely; renal failure

is rare. Laboratory features consistent with the diagnosis include transient low serum complement levels. The antistreptolysin O titer is positive in 90% of children after a respiratory infection but in only 50% of patients who have had skin infections. Antibiotic treatment of streptococcal pharyngitis or impetigo does not reduce the risk of poststreptococcal glomerulonephritis, although the risk of rheumatic fever is reduced.
5. The answer is D [VI.A, VI.B, VI.E, and VI.G.5]. Nephrotic syndrome in children is defined as heavy proteinuria (>50 mg/kg/24 hours), hypoalbuminemia, hypercholesterolemia, and edema. Patients with nephrotic syndrome are susceptible to infections with encapsulated organisms, such as pneumococcal infections, and are at risk for developing peritonitis, pneumonia, and overwhelming sepsis. Patients with nephrotic syndrome and fever should therefore be treated empirically with antibiotics pending culture results. The most common form of nephrotic syndrome in children is minimal change disease, which comprises 90% of all cases. Primary glomerular disease (e.g., IgA nephropathy) and systemic diseases (e.g., systemic lupus erythematosus) are less common causes of nephrotic syndrome in children. Most cases of childhood nephrotic syndrome (two-thirds) occur in children younger than
5 years of age. Renal biopsy to establish the diagnosis or to determine a management approach is not indicated for most patients with nephrotic syndrome. However, it is indicated for patients who have impaired creatinine clearance or for those who do not respond to initial management with corticosteroids.
6. The answer is E [VII.C.3]. There are three subtypes of hemolytic uremic syndrome (HUS), a Shiga toxin–associated form (the most common form in childhood), pneumococcal- associated form, and an atypical form caused by medications or complement system dysregulation which is often inherited. Shiga toxin–associated HUS occurs as a result of intestinal infection with a toxin-producing bacterial strain, most commonly Escherichia coli 0157:H7. The toxin binds to vascular endothelial cells, especially in the renal vasculature, causing platelet thrombi and resultant renal ischemia. Patients with HUS have a microangiopathic hemolytic anemia, renal impairment, and thrombocytopenia, which may result in visible petechiae on the skin. The prognosis for patients with Shiga toxin–associated HUS is generally good, although poor prognostic signs include elevated white blood cell count on admission and prolonged oliguria. Antibiotic treatment of the E. coli hemorrhagic colitis is controversial and may actually increase the likelihood that a patient will go on to develop HUS.
7. The answer is C [V.F.2]. This patient’s clinical presentation and ethnicity are consistent with IgA nephropathy (Berger disease), the most common form of chronic glomerulonephritis in the world. Patients with IgA nephropathy typically present in the second or third decade of life with recurrent bouts of gross hematuria associated with respiratory infections. IgA nephropathy is most common in Asia and Australia and in Native Americans. Membranoproliferative nephritis, membranous nephropathy, and nephritis as a result of systemic lupus erythematosus during childhood are all less common causes of glomerulonephritis in children. This patient’s clinical presentation is not consistent with Henoch–Schönlein purpura, which is characterized by abdominal pain, palpable purpura on the buttocks and thighs, and joint symptoms.
8. The answer is D [XII.E]. Vesicoureteral reflux (VUR) is caused by abnormalities of the ureterovesical junction, most commonly a shortened submucosal tunnel in which the ureter inserts through the bladder wall. The inheritance pattern is most commonly autosomal dominant with variable expression but autosomal recessive inheritance has also been described. The majority of children with VUR eventually outgrow the reflux, although a minority develop severe renal impairment owing to reflux nephropathy from severe VUR. Patients with grade 4 or 5 VUR should be referred to a pediatric urologist for consideration of ureteral reimplantation. Although previously recommended, low-dose prophylactic antibiotics to decrease the risk of urinary tract infection in low risk patients is not indicated.

9. The answer is E [I.B and I.C]. Maintenance water and electrolyte calculations are designed to balance the usual daily losses of water and salts as a result of normal daily metabolic activities. These losses include both measurable forms (sensible losses), such as urinary losses, and less readily measurable but still clinically significant forms (insensible losses), such as losses from the skin, lungs, or gastrointestinal tract. The maintenance sodium requirement is approximately 2–3 mEq/kg/day for infants and children. When calculating maintenance fluids using the surface area method, the maintenance water requirement for children is
1500 mL/m2/day. Fever will result in increased insensible losses, and maintenance fluids should be increased by about 10% for every degree of temperature above 38°C. Maintenance fluid calculations should not be adjusted for increased ongoing losses, such as profuse watery diarrhea. Instead, any increased stool losses should be replaced on a “milliliter per milliliter” basis.
10. The answer is E [Figure 11-2 and Table 11-3]. This patient likely has a renal vein thrombosis, which presents in infancy with the sudden onset of gross hematuria and unilateral or bilateral flank masses. Acute renal failure may result. Infants of diabetic mothers have a greatly increased risk of renal vein thrombosis. Maternal systemic lupus erythematosus (SLE) would not result in hematuria in the infant; however, maternal SLE is associated with infant heart block. Adenovirus infection is a cause of hemorrhagic cystitis, which often causes hematuria; however, this would be very unusual in a neonate. Similarly, although sickle cell disease also causes hematuria, it would be an uncommon presentation in a neonate. Hypercalciuria is a common cause of hematuria; however, a flank mass would not be a presenting sign.
11. The answer is C [IX.E and Table 11-2]. The classic electrolyte presentation seen in renal tubular acidosis (RTA) is a hyperchloremic metabolic acidosis with a normal serum anion gap. Hypokalemia is not specifically associated with RTA; however, type IV RTA is associated with hyperkalemia. Patients with Fanconi syndrome may present with proximal (type II) RTA with glucosuria, aminoaciduria, and hyperphosphaturia (therefore low serum phosphorus levels, not high serum phosphorus levels). Hypocalcemia is not a feature of RTA.
12. The answers are B, A, and D, respectively [VIII.D, VIII.E, and VIII.B]. Infantile polycystic kidney disease (question 12) is an autosomal recessive disorder characterized by greatly enlarged cystic kidneys, severe hypertension, and variable degrees of liver involvement. Severe cases are associated with oligohydramnios, pulmonary hypoplasia, and early neonatal death. Although the family history may be negative in recessive disorders, there is a 25% risk of affected siblings in subsequent pregnancies. In contrast, adult polycystic kidney disease (question 13) is inherited in an autosomal dominant pattern, and there is considerable variability in its severity, ranging from mild microscopic hematuria to severe hypertension and renal failure. Adult polycystic kidney disease may also be associated with cerebral aneurysms and early death. Alport syndrome (question 14) is inherited in multiple patterns, but the X-linked form is by far the most common. Alport syndrome is characterized by renal manifestations, including hypertension and hematuria, as well as renal failure more consistently in the males; hearing loss; and ocular abnormalities of the lens and retina.