Pediatric Residency Training Program

11

Nephrology and Urology

Elaine S. Kamil M.D.

Lee Todd Miller M.D.

  1. Fluids, Electrolytes, and Dehydration
  2. General Principles
  3. The most common cause of acute fluid and electrolyte imbalance is acute diarrhea with dehydration.
  4. Worldwide, acute diarrheal diseases are one of the leading causes of childhood morbidity and mortality, accounting for more than 5 million childhood deaths each year.
  5. Patients with acute dehydration may be managed with both parenteral rehydration and oral rehydration therapy.
  6. Total body fluid requirement is the sum of a patient's maintenance fluid needs, plus replacement of prior fluid losses (i.e., deficits), plus replacement of ongoing losses

if any.

  1. Maintenance water and electrolyte calculationsare 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.
  2. Maintenance water requirement isapproximately 1, 500 mL/m2/d for children.
  3. Maintenance water requirement may alternatively be calculatedfrom the patient's weight:
  4. 100 mL/kg/dayfor the first 10 kg of body weight
  5. 50 mL/kg/dayfor the second 10 kg of body weight
  6. 20 mL/kg/dayfor each kg above the first 20 kg of body weight
  7. Maintenance fluids should be increasedif the patient has increased insensible losses, such as respiratory distress and fever (i.e., a 12% increase for every degree of temperature above 38°C.
  8. Maintenance sodium (Na+) requirement is approximately 2–3 mEq/kg/d.

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  1. Maintenance potassium (K+) requirementis approximately 2 mEq/kg/d during infancy but decreases with age.
  2. Deficit fluid calculationsare designed to replace abnormal losses of water and salts caused by pathologic states, such as diarrhea and vomiting.
  3. Ongoing loss calculationsare 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.
  4. Dehydration may be classified

by both the initial serum Na+ level and by the degree of dehydration.

  1. Classification by serum sodium concentration
  2. Hyponatremicdehydration (Na+ < 130 mmol/L)
  3. Isonatremicdehydration (Na+ 130–150 mmol/L)
  4. Hypernatremicdehydration (Na+ > 150 mmol/L)
  5. Classification by degree of dehydration
  6. Milddehydration (3–5%)
  7. Moderatedehydration (7–10%)
  8. Severedehydration (≥ 12%)
  9. Parenteral rehydration

should occur in two phases:

  1. Emergency phase
  2. The goal of the emergency phaseis to restore or maintain the intravascular volume to ensure perfusion of vital organs.
  3. The emergency phase is the same for all patients, regardless of the patient's initial serum sodium level.
  4. 20 mL/kg bolusesof intravenous (IV) solutions with a high enough oncotic load (e.g., normal saline or lactated Ringer's) are commonly used.
  5. Repletion phase
  6. The goal of the repletion phaseis a more gradual correction of the patient's water and electrolyte deficits.
  7. Patients with the acute onset of hyponatremic or isonatremic dehydrationgenerally have their fluid and electrolyte deficits replaced over 24 hours. Chronic hyponatremia should be corrected much more slowly.
  8. Patients with hypernatremic dehydrationgenerally 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.
  9. Oral Rehydration Therapy (ORT)
  10. ORT may be an effective, safe, and inexpensive alternativeto IV rehydration therapy.
  11. Oral rehydration salt (ORS) solutionsare balanced mixtures of glucose and electrolytes for use in treating and preventing dehydration, potassium depletion, and base deficits caused by diarrhea.

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  1. ORT is based on the principle that the intestinal absorption of sodium and other electrolytes is enhanced by the active absorption of glucose (coupled co-transport mechanism). This coupled co-transport process of intestinal absorption continues to function normally during secretory diarrhea, whereas other pathways of intestinal absorption of sodium are impaired.
  2. ORT is inappropriatefor 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.
  3. Hematuria
  4. 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 ≥ 6 RBCs per high-power field (HPF) detected on three or more consecutive samples.

  1. Epidemiology

Between 4 and 5% of school children have microscopic hematuria detected on a single voided urine sample, but only 0.5–2% have persistent microscopic hematuria.

  1. 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. Thedifferential diagnosis of hematuria is outlined in Figure 11-1.

  1. Evaluation

(Figure 11-2). 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. Urinalysis may also provide clues. When RBCs are present on microscopic examination, careful examination of RBC morphology and identification of other urine elements may be extremely helpful in determining the cause of the hematuria.

  1. RBC castsare diagnostic of glomerular bleeding, which usually occurs in acute or active glomerulonephritis.
  2. RBC morphology
  3. RBCs originating in the glomerulus are dysmorphic in character, often with blebs in the RBC membrane.
  4. RBCs that appear to be normal biconcave disks usually originate in the lower urinary tract.
  5. The presence of other clues in the urine may also point to a diagnosis.
  6. Crystalsmay be indicative of renal stone disease.
  7. 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).

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Figure 11-1. Differential diagnosis of hematuria.

III. Proteinuria

  1. Definition

Whereas a small amount of protein is normally present in the urine, proteinuria greater than 100 mg/m2/day is considered pathologic.

  1. Detection
  2. Urinary dipstickis the most frequently used method of screening for proteinuria and detects variable levels of albuminuria.
  3. False positivesmay 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, oral hypoglycemic agents).

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  1. False negativesmay result if the urine is very dilute.
 

Figure 11-2. An approach to red urine. RBC = red blood cell; U/A = urinalysis

  1. 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.
  2. Normal urine TP/CR for infants 6–24 months is < 0.5.
  3. Normal urine TP/CR for children > 2 years is < 0.2.
  4. Epidemiology

Two to eleven percent of children have a single positive dipstick test for proteinuria at some point; however, <1% have persistent proteinuria on repeated dipstick evaluations.

  1. Classification
  2. Benign transient proteinuria.Increased urinary protein excretion may sometimes be associated with vigorous exercise, fever, dehydration, and congestive heart failure.
  3. Orthostatic proteinuria
  4. Certain children and adults (especially athletic individuals) have increased urinary protein excretion while upright, but not while supine.

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  1. Orthostatic proteinuria is usually a benign conditionand its confirmation eliminates the need for further workup.
  2. 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
  4. Persistent pathologic proteinuria may be associated with significant renal disease and is considered a marker for progression of renal disease.
  5. Generally, the greater the magnitude of the proteinuria, the more serious the renal disease.The highest amounts of proteinuria are seen in patients with nephrotic syndrome (see section V).
  6. Persistent pathologic proteinuria may have a glomerularorigin or a tubular origin. Glomerular proteinuria is more common.
  7. Glomerular proteinuriais caused by increased permeability of the glomerular capillaries to large molecular weight proteins, as seen in glomerulonephritis (see section IV).
  8. Tubular proteinuriaresults from decreased reabsorption of low molecular weight proteins by the tubular epithelial cells.
  9. Examples of tubular proteinuriainclude interstitial nephritis, ischemic renal injury (acute tubular necrosis), and tubular damage resulting from nephrotoxic drugs.
  10. Laboratory findingsinclude elevated levels of urinary β2-microglobulin, a good marker for tubular proteinuria. 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.
  11. Evaluation of Proteinuria

(Figure 11-3)

  1. Glomerulonephritis
  2. Definition

Glomerulonephritis refers to a group of diseases that cause inflammatory changes in the glomeruli.

  1. 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.

  1. Classification
  2. Primary glomerulonephritisrefers to a disease process limited to the kidney.
  3. Secondary glomerulonephritisrefers to a disease process that is part of a systemic disease (e.g., systemic lupus erythematosus).
  4. Clinical features

Presentation is variable.

  1. Some patients present with an acute “nephritic” syndromecharacterized by gross hematuria, hypertension, and occasionally signs of fluid overload from renal insufficiency.

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  1. Some patients may present with glomerulonephritis associated with nephrotic syndromewith heavy proteinuria, hypercholesteremia, and edema.
 

Figure 11-3. Evaluation of proteinuria.

  1. Some patients may be relatively asymptomatic, in whom glomerulonephritis is only detected as part of the evaluation of microscopic hematuria, proteinuria, or hypertension.

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  1. Laboratory Evaluation

Laboratory studies should be performed promptly to avoid missing key transient abnormalities (e.g., transient decrease in serum complement seen in poststreptococcal glomerulonephritis).

  1. Initial evaluationshould include urinalysis (to look for casts and to evaluate RBC morphology), urinary TP/CR (to quantify proteinuria), blood chemistries (including electrolyte panel, blood urea nitrogen [BUN], creatinine, serum albumin, liver enzymes, and cholesterol), serum complement componentsantibody testing (antinuclear antibody [ANA], 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 HIV testing, hepatitis C and hepatitis B serologies to evaluate for other causes of postinfectious glomerulonephritis, and other autoimmune markers.
  3. Common Types of Glomerulonephritis in Children
  4. Poststreptococcal glomerulonephritis
  5. Epidemiology. Poststreptococcal glomerulonephritis (PSGN)is the most common form of acute glomerulonephritis that occurs in school-age children. (Note that other less common causes of postinfectious glomerulonephritis include HIV and hepatitis B and C.) PSGN is rare before 2 years of age.
  6. Clinical features
  7. PSGN develops 8–14 days after an infection of the skin or pharynxwith a nephritogenic strain of group A β-hemolytic streptococcus. The latency period after impetigo may be as long as 21–28 days.
  8. Hematuria(often gross hematuria), proteinuria (rarely of nephrotic proportion), and hypertension with signs of fluid overload (e.g., edema) are common clinical features.
  9. Low serum complement(C3) is present but transient, and normalizes within 8–12 weeks.
  10. Degree of impairment of renal function is variable and usually normalizes within 6–8 weeks. Severe renal failure is rare.
  11. Diagnosis.Diagnosis is on the basis of clinical features and laboratory findings, including evidence of prior streptococcal infection.
  12. Detection of prior streptococcal infection
  13. ASO titeris positive in 90% of children after streptococcal pharyngitis, but is positive in only 50% of patients with impetigo.
  14. ADB titeris reliably positive after respiratory or skin infections with streptococcus.
  15. Other diagnostic testsshould include urinalysis, serum complement levels, renal ultrasound, tests of renal function, serum albumin, and serum cholesterol if the serum albumin is depressed.
  16. Renal biopsyis indicated only if the patient has significant renal impairment or nephrotic syndrome, or if the serum complement fails to normalize within 8 weeks. Biopsytypically shows mesangial cell proliferation and increased mesangial matrix.

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  1. Management.Treatment is supportive in most cases, and includes fluid restriction, antihypertensive medications, and dietary restriction of protein, sodium, potassium, and phosphorus.
  2. Prognosisis excellent with complete recovery in most patients.
  3. Prompt antibiotic treatment of infections with nephritogenic strains of group Aβ-hemolytic streptococcus does not reduce the risk of poststreptococcal glomerulonephritis, although it will reduce the risk of rheumatic fever (see Chapter 16, section VI and Chapter 7, section IX.A.5.f).
  4. IgA nephropathy (Berger's disease)
  5. Epidemiology
  6. IgA nephropathy is the most common type of chronic glomerulonephritis worldwide.It typically presents in the second or third decade of life.
  7. It is more prevalent in Asiaand Australia and in Native Americans, and it is rare in African Americans.
  8. Etiology.The cause is poorly understood but may relate to abnormal clearance or formation of IgA immune complexes.
  9. Clinical features.Clinical findings classically include recurrent bouts of gross hematuria associated with respiratory infections. Transient acute renal failure may occur in some patients. Microscopic hematuria is present in between the bouts of gross hematuria.
  10. 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.
  11. Management.Treatment is supportive, and medications (angiotensin-converting enzyme [ACE] inhibitors, steroids, and immunosuppressants) usually are only recommended for patients with associated pathologic proteinuria or renal insufficiency.
  12. Prognosisis variable. Twenty to forty percent of patients eventually develop end-stage renal disease.
  13. Henoch-Schönlein purpura (HSP) nephritis(see Chapter 16, section I)
  14. Definition.HSP is an IgA-mediated vasculitis characterized by nonthrombocytopenic “palpable purpura” on the buttocks and thighs, abdominal pain, arthritis or arthralgias, and gross or microscopic hematuria.
  15. Clinical features.Clinical findings related to renal involvement include:
  16. If proteinuria is present, it may suggest severe glomerular inflammation. Renal biopsy is indicated for heavy or nephrotic-range proteinuria.
  17. 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.

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  1. Membranoproliferative glomerulonephritis (MPGN)
  2. 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.
  3. Clinical features
  4. Patients typically present with nephritis, or with nephrotic syndrome accompanied by microscopic or gross hematuria.
  5. Hypertension is common.
  6. Seventy-five percent of patients have low serum complement levels.
  7. Clinical course is variable, although most patients ultimately develop end-stage renal disease.
  8. Management.There is no definitive treatment for MPGN, although some patients may respond to corticosteroids. ACE inhibitors may slow disease progression.
  9. Membranous nephropathy (MN)is a rare form of glomerulonephritis in young children, although it may be seen in adolescents. MN presents with heavy proteinuria and often progresses to renal insufficiency. MN is the most common cause of nephrotic syndrome in adults in the United States.
  10. Systemic lupus erythematosus nephritis(see Chapter 16, section IV.D.8)
  11. Nephrotic Syndrome (NS)
  12. Definition

NS is a condition characterized by heavy proteinuria (> 50 mg/kg/24 hours), hypoalbuminemia, hypercholesterolemia, and edema.

  1. Epidemiology
  2. Two thirds of cases present before 5 years of age.
  3. In young children, the ratio of boys to girls is 2:1. By late adolescence, both sexes are equally affected.
  4. 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 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 IgA nephropathy, MPGN, and PSGN
  3. NS that results from systemic diseases, including systemic lupus erythematosus and HSP
  4. Pathophysiology
  5. The basic physiologic defect is a loss of the normal charge- and size-selective glomerular barrier to the filtration of plasma proteins.

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  1. Excessive urinary protein losses lead to the hypoproteinemia of NS.
  2. Hypercholesterolemia is a consequence of the hypoproteinemia.
  3. Reduced plasma oncotic pressure induces increased hepatic production of plasma proteins, including lipoproteins.
  4. Plasma lipid clearance is reduced because of reduced activity of lipoprotein lipase in adipose tissue.
  5. Clinical Features
  6. 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.
  7. Patients may rarely be asymptomatic at the time of diagnosis. In these patients, NS is diagnosed during an evaluation for asymptomatic proteinuria.
  8. Patients are predisposed to thrombosissecondary to hypercoagulability. Patients may present with stroke or other thrombotic events such as renal vein thrombosis, deep vein thrombosis, and sagittal sinus thrombosis.
  9. Patients are also at an increased riskfor infection with encapsulated organisms, such as Streptococcus pneumoniae, and therefore may present with spontaneous bacterial peritonitis, pneumonia, or overwhelming sepsis.
  10. Diagnosis

Diagnosis is on the basis of clinical features and on the following studies:

  1. Urinalysistypically reveals 3+ to 4+ protein, sometimes microscopic hematuria, and an elevated urinary TP/CR. The presence of RBC casts indicates a cause other than MCD.
  2. Complete blood count (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 renal tubular acidosis. Hypoalbuminemia and elevated serum cholesterol are present. BUN and creatinine should be measured to assess for renal impairment.
  4. C3, ANA, and antistreptococcal antibodiesare indicated to rule out causes of NS other than MCD.
  5. Renal ultrasoundoften shows enlarged kidneys.
  6. Renal biopsyis rarely indicated in the child with typical NS unless the creatinine clearance is impaired or initial management with corticosteroids is ineffective.
  7. Management

Treatment is dictated by the underlying cause of the NS, but supportive therapy is universally indicated.

  1. Most children are hospitalized for initial treatment, although a relatively asymptomatic child with a reliable caregiver can be followed carefully as an outpatient.

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  1. If the child has widespread edema, scrotal or labial edema, hypotension, or symptomatic pleural effusions, IV infusions of 25% albuminshould be given to achieve a diuresis and to maintain the intravascular volume.
  2. The dietshould consist of meals with no added salt.
  3. Most patients with MCD respond to therapy with corticosteroids.Steroid-dependent or steroid-resistant patients may respond to cyclophosphamide or cyclosporine.
  4. 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.
  5. Prognosis

varies according to the underlying cause.

  1. Mortality approaches 5%, almost exclusively in children who are steroid-resistant, and almost always from overwhelming infectionor thrombosis.
  2. In the majority of children with steroid-sensitive NS, relapses typically occur with varying frequency but often disappear by the completion of puberty. Less than 10% of children who are initially steroid-sensitive develop end-stage renal disease (ESRD), resulting in focal sclerosing glomerulosclerosis (FSGS).In contrast, a majority of patients with steroid-resistant or steroid-dependent NS eventually develop ESRD.
  3. Hemolytic Uremic Syndrome (HUS)

(see Chapter 13, section I.F.2.b.(3) and Chapter 7, Table 7-6)

  1. Definition

HUS is a condition characterized by acute renal failure in the presence of microangiopathic hemolytic anemia and thrombocytopenia.

  1. Subtypes

There are two different subtypes of HUS, which differ in their known etiology, treatments, and prognoses.

  1. Shiga toxin-associated HUS (Stx HUS)
  2. Epidemiology.Stx HUS is the most common subtype seen in childhood.
  3. Etiology
  4. Stx HUS occurs as a result of intestinal infection with a toxin-producing bacteria.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.
  5. Known sources of infection include undercooked beef, unpasteurized milk, and contaminated fruit juices. Human-to-human transmission has been described.
  6. Pathogenesis
  7. Vascular endothelial injury by the shiga toxin is the key to the pathogenesis of injury in Stx HUS.

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  1. The toxin binds to endothelial cells, causing endothelial cell injury, most especially in the renal vasculature, leading to platelet thrombi formation and renal ischemia.
  2. Clinical features.Clinical presentation is of a diarrheal prodrome (often bloody and may be severe) followed by the sudden onset of hemolytic anemia, thrombocytopenia, and acute renal failure.
  3. Management. Treatment is supportive.
  4. Transfusions are given as needed for severe anemia and thrombocytopenia.
  5. Acute renal failure is managed as described in section X.E.
  6. Antibiotics are not indicated for HUS.In addition, antibiotic treatment of E. coli hemorrhagic colitis may increase the likelihood that the patient will eventually develop HUS.
  7. Prognosis.The prognosis is generally favorable and depends on the severity of the presentation.
  8. Poor prognostic signsfor renal recovery include a high white blood cell (WBC) count on admission and prolonged oliguria.
  9. 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.
  10. Atypical HUS
  11. Epidemiology.Atypical HUS is much less common than Stx HUS.
  12. Etiology
  13. Drugs(e.g., oral contraceptives, cyclosporine, tacrolimus, and OKT3) may cause atypical HUS.
  14. Inheritedatypical HUS has also been described, with both autosomal dominant and autosomal recessive inheritance patterns.
  15. Clinical features.Clinical findings are similar to those of Stx HUS, although diarrhea is absent and severe proteinuria and hypertension are more consistently present.
  16. Management. Treatment is supportive.Inciting medications, if any, must be stopped immediately.
  17. Prognosis.Some patients have a chronic relapsing course (recurrent HUS). All patients with atypical HUS have a higher risk of progression to ESRD than patients with Stx HUS.

VII. Hereditary Renal Diseases

  1. General Concepts

Because many inherited renal diseases present in childhood, a careful family history is critical in all children with renal disease.

  1. Alport's Syndrome
  2. Definition.Alport's 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.

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  1. Etiology. Inheritanceis usually X-linked dominant, although autosomal dominant and autosomal recessive variants exist.
  2. Clinical features
  3. Renal manifestationsinclude hypertension and hematuria. ESRD may occur (most commonly in males).
  4. Hearing losstypically begins in childhood and progresses; approximately 50% of adults have some loss of hearing, ranging from mild to severe.
  5. Ocular abnormalitiesinvolving the lens and retina occur in 25–40% of patients.
  6. Management.Therapy includes treatment of hypertension, use of ACE inhibitors to slow the progression of renal disease, and eventually renal transplantation.
  7. Multicystic Renal Dysplasia

This condition is the most common cause of a renal mass in the newborn, occurring in 1 in 4, 300 live births, and is most often unilateral. The inheritance is not clear, but it appears to be a sporadic occurrence. See section XI.D.2 for more details.

  1. Autosomal Recessive Polycystic Kidney Disease (ARPKD) or Infantile Polycystic Kidney Disease
  2. Epidemiology.ARPKD is uncommon, occurring in approximately 1 in 10, 000 to 1 in 40, 000 live births.
  3. Clinical features
  4. The most severely affected infants have a maternal history of oligohydramniossecondary to nonfunctioning or poorly functioning kidneys. This leads to pulmonary hypoplasia.
  5. Greatly enlarged cystic kidneys
  6. Severe hypertensionis common.
  7. Liver involvementof variable clinical severity is a constant finding, including cirrhosis with portal hypertension.
  8. Prognosis.Whereas the degree of renal insufficiency in infancy may range from mild to severe, ARPKD is progressive and ultimately all patients require renal transplantation.
  9. Autosomal Dominant Polycystic Kidney Disease (ADPKD) or Adult Polycystic Kidney Disease
  10. Epidemiology.ADPKD is a common genetic disorder (affecting 1 in 600 individuals) that usually presents in adulthood (20–40 years of age).
  11. 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.
  12. Prognosis.Most patients develop severe hypertension and renal insufficiency, eventually requiring transplantation.
  13. Medullary Sponge Kidney

This condition occurs sporadically or may have autosomal dominant inheritance. Patients may be asymptomatic or have hematuria, UTI, or nephrolithiasis.

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  1. Nephronophthisis-Medullary Cystic Disease Complex (NPH-MCD)

This histologic entity occurs in several forms. The juvenile form is autosomal recessive and leads to ESRD in childhood, and the adult form is autosomal dominant and causes renal failure later in life.

VIII. Hypertension

  1. Definitions
  2. Normal blood pressuresduring 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).
  3. Normal systolic and diastolic blood pressuresare defined as blood pressure less than the 90th percentile for age.
  4. Normal high blood pressuresare between the 90th and 95th percentiles for age.
  5. Classification

Hypertension is divided into categories based on severity and etiology.

  1. Significant hypertensionis defined as the average of three separate blood pressures that are greater than the 95th percentile for age.
  2. Severe hypertensionis defined as the average of three separate blood pressures that are greater than the 99th percentile for age.
  3. Malignant hypertensionis hypertension associated with evidence of end-organ damage, such as retinal hemorrhages, papilledema, seizures, and coronary artery disease (in adults).
  4. Essential hypertensionis defined as hypertension without a clear etiology.
  5. Secondary hypertensionis hypertension that has a recognizable cause (e.g., renal parenchymal disease, coarctation of the aorta). Most hypertension in childhood is secondary hypertension.
  6. Measurement
  7. Blood pressure cuff size
  8. It is critical to use the proper size cuff. A cuff that is too smallwill give factitiously elevated blood pressures, and a cuff that is too large will give falsely depressed blood pressures.
  9. The cuff bladder should measure two thirds of the length of the arm from the shoulder to the elbow.
  10. Position
  11. Blood pressure in infants should be measured in the supine position.
  12. 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.
  13. Etiology (Table 11-1)

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.

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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 diseases

Coarctation of the aorta

 

Endocrine disorders

Neuroblastoma
Pheochromocytoma
Congenital adrenal hyperplasia
Hyperthyroidism

Hyperparathyroidism
Hyperaldosteronism
Cushing's 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

 

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.

  1. In children 1–10 years of age, the most common causes include renal diseases and coarctation of the aorta.
  2. In adolescents, the most common causes include renal diseases and essential hypertension.
  3. Clinical features. Clinical presentations of hypertension

also vary with the child's age. Some children, like some adults, are asymptomatic.

  1. Infantsmay present with nonspecific signs and symptoms including irritability, vomiting, failure to thrive, seizures, or even congestive heart failure (CHF) if the hypertension is severe.
  2. Childrenwith malignant hypertension, especially of acute onset, may develop headaches, seizures, and stroke.
  3. Childrenwith chronic hypertension may frequently have growth retardation and poor school performance.
  4. 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
  2. All children should undergo an assessment of growth and careful, accurate measurements of four limb blood pressuresto 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.
  3. In children, a careful funduscopic examinationmay show retinal hemorrhages, papilledema, or, in long-standing hypertension, arterial-venous nicking.
  4. Other important physical findings include signs of CHF, café-au-lait spots as seen in neurofibromatosis, abdominal masses, abdominal bruits, or ambiguous genitalia.
  5. Laboratory evaluation and imaging
  6. Initial evaluationshould include a CBC, electrolyte panel, BUN and creatinine, urinalysis, plasma renin, chest radiograph, and renal ultrasound.
  7. If the initial evaluation is suggestive, further studies may include a thyroid panel, plasma catecholamines, measurement of plasma and urinary steroids, and echocardiography. Radioisotope renal scan with the administration of captopril or renal angiography identifies renal artery stenosis.
  8. 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 well 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

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of hyperthyroidism, or removal of a catecholamine-secreting tumor, is performed as a cure.

  1. 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.
  2. If the child has underlying renal diseaseor severe hypertension, or if conservative hypertension treatment has failed, antihypertensive medications are used.
  3. Hypertensive emergencies(e.g., seizures, severe headache, stroke, funduscopic changes, CHF) require prompt therapy with intravenous antihypertensives.
  4. Renal Tubular Acidosis (RTA)
  5. Definition

Renal tubular acidosis 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.

  1. Etiology

(Table 11-2)

  1. Congenital formsof RTA are caused by mutations in various transporters in the proximal or distal tubular cells.
  2. Acquired formsof RTA may be caused by nephrotoxic drugs (e.g., amphotericin) or systemic diseases (e.g., autoimmune disorders).
  3. Clinical Features

(see Table 11-2). Symptoms vary with the type of RTA and with the patient's age.

  1. Infants and young childrentend to present with growth failure and vomiting, and at times with life-threatening metabolic acidosis.
  2. Older children and adultsmay 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. Classic electrolyte presentationis a hyperchloremic metabolic acidosis with a normal serum anion gap.
  5. Types of RTA

(see Table 11-2)

  1. 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 studiesshould include serum potassium and phosphorus, 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 distal RTA.
  2. If there are signs of a diffuse tubular disorder (manifested by hypokalemia,

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hypophosphatemia, and aminoaciduria), the patient should be evaluated for Fanconi syndrome (see Table 11-2) 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
Associated with drugs (amphotericin)

Vomiting
Growth failure
Acidosis
If untreated, nephro-calcinosis and nephro-lithiasis

Small doses of oral alkali

Proximal RTA (Type II)

Impaired bicarbonate reabsorption by the proximal renal tubular cells

Isolated defect
Intoxication (heavy metals)
Drugs (gentamicin)
Associated with more global defects in tubular reabsorption (Fanconi syndrome*)

Vomiting
Growth failure
Acidosis
Muscle weakness

Large doses of oral alkali

Type III RTA

Avariant of type I, complicated by proximal tubular bicarbonate wasting during infancy

 

 

Large doses of oral alkali

Type IV RTA

Transient acidosis in infants and children
Hyperkalemia is the hallmark

Associated with renal disorders such as obstructive uropathy
Associated with aldo-sterone deficiency states

Patients may be asymptomatic, or may present with failure to thrive

Furosemide to lower serum potassium; oral alkali

*Findings associated with Fanconi syndrome: proximal RTA, hyperphosphaturia, aminoaciduria, glucosuria, and potassium wasting.

  1. Renal Failure
  2. Definition. Acute renal failure

(ARF) is defined as an abrupt decrease in the ability to excrete nitrogenous wastes.

  1. Etiology

(Table 11-3)

  1. Clinical Features
  2. 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.
  3. The clinical presentation may be oliguric (diminished urine output) or nonoliguric (normal urine output). In children, oliguriais defined as a urine output < 1 mL/kg/hr.
  4. Evaluation
  5. Laboratory testsshould include serum electrolytes, BUN, creatinine, urinalysis, and urinary protein and creatinine levels.
  6. Imaging studiesmay include a renal or pelvic ultrasound and a nuclear renal scan to evaluate renal function.
  7. Management
  8. If possible, the specific cause should be addressed (e.g., removal of a nephrotoxic drug).
  9. If the patient is intravascularly volume depleted, the intravascular volume should be restored first, and then total fluid intake should be restricted to the patient's insensible losses (approximately 300 mL/m2/day) plus output (urine, stool) replacement.
  10. Electrolyte intake should be matched to estimated electrolyte losses.Typically, sodium, potassium, and phosphorus intake are restricted.
  11. Protein intake should be restrictedto the recommended dietary allowance (RDA) of protein for age. Caloric intake should also be at the RDA for age.
  12. Patient monitoringshould include daily weights, frequent blood pressure measurements, calculation of intake and output, and monitoring of electrolytes.
  13. Dialysis therapy(peritoneal dialysis or hemodialysis) is used when conservative management fails to maintain the patient in safe biochemical, nutritional, and fluid balance.
  14. Chronic Renal Insufficiency and End-Stage Renal Disease (ESRD)
  15. Etiology
  16. The most common causesinclude glomerular diseases (e.g., FSGS), congenital or inherited kidney diseases (e.g., renal dysplasias or obstructive

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uropathies), reflux nephropathy, collagen vascular diseases, cystic kidney diseases, interstitial nephritis, and HUS.

Table 11-3. Etiologies of Acute Renal Failure (ARF)

Categories of ARF

Causes of Renal Failure

Specific Examples

Laboratory Findings

Prerenal

Caused by a reversible ↓ in renal perfusion that leads to a ↓ in GFR

Dehydration
Hemorrhage
Congestive heart failure
Septic shock
Hypoproteinemic states

↓ BUN/Creat ratio > 20
↓ Urine SG ≥ 1.030
Urine osmolality 500 > Urine Na+ < 20
*FENa < 1% in older children, < 2.5% in neonates

Renal parenchymal

Damage to glomerulus

PSGN
Lupus nephritis
HUS

Hematuria
Proteinuria

 

Damage to tubules (acute tubular necrosis)

Ischemic injuries from renal hypoperfusion

↓ Urinary β2-microglobulin
FENa > 1% in children, > 2.5% in neonates

Postrenal

Obstruction of urine flow from either a solitary kidney, from both kidneys, or from the urethra

Stones
Tumor
Ureterocele
Urethral trauma
Neurogenic bladder
Posterior urethral valves in males

Dilation of renal collecting system on renal ultrasound

Vascular

↓ Perfusion of the kidneys

Renal artery embolus (especially in the presence of an umbilical artery catheter)
Renal vein thrombosis, presenting with sudden-onset gross hematuria and a unilateral or bilateral flank mass, with ↓ incidence in infants of diabetic mothers

↓ Renal blood flow on nuclear renal scan

 

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.

  1. The cause is unknown in up to 10% of cases.
  2. Determining the cause of the child's chronic renal insufficiency may have implications for the child and his or her family. Specific therapies may modify disease progression, some genetic diseases may occur in siblings or offspring, and some diseases may recur in transplanted kidneys.
  3. Clinical features.Clinical findings may include short stature, anemia, failure to thrive, polyuria and polydipsia, lethargy, and rickets.
  4. Evaluation
  5. Investigation for the causes of ARF (Table 11-3)
  6. Careful family history
  7. Assessment of growth and nutrition
  8. Evaluation for renal osteodystrophy (i.e., bone disease secondary to renal failure)
  9. Serologic testing for collagen vascular diseases
  10. Renal imaging to look for structural kidney abnormalities
  11. Renal biopsy (in some cases)
  12. Management
  13. Medical
  14. Nutritional managementincludes 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 analogs to prevent renal osteodystrophy. Protein intake should be at the RDA for age.
  15. Biochemical managementincludes monitoring and management of serum electrolytes, BUN, creatinine, calcium, and alkaline phosphatase.
  16. Blood pressuremonitoring and management are critical.
  17. Anemiais treated with iron and recombinant erythropoietin therapy.
  18. Growthis closely monitored, and patients may require recombinant human growth hormone if their growth fails to normalize with other medical interventions.
  19. Dialysisis initiated or transplantation is considered when the glomerular filtration rate is 5–10% of normal.
  20. Peritoneal dialysisis generally the preferred dialysis modality in infants and children.
  21. Chronic hemodialysismay also be performed in children and requires vascular access via an indwelling catheter or an arteriovenous fistula.
  22. Kidney transplantationis the preferred treatment for children with ESRD.
  23. Living-related donors and living-unrelated donors are preferred over cadaveric donors because of better kidney transplant outcome. Graft outcome varies with donor source.

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Approximately 80% of living donor kidneys and 65% of cadaveric kidneys remain functioning 5 years after transplant.

  1. Kidney transplantation requires lifelong immunosuppression with increased risks of infection and subsequent malignancies.
  2. The most common causes of transplant lossinclude acute and chronic rejection, noncompliance with medications, technical problems during surgery, and recurrent disease.
  3. Structural and Urologic Abnormalities

A

Structural and urologic abnormalities are common, occurring in 6–10% of children.

  1. Congenital obstructive abnormalities

may occur at any level in the urinary tract. Bilateral lesions may threaten renal function.

  1. Ureteropelvic junction obstructionmay occur as a result of kinks, fibrous bands, or overlying aberrant blood vessels.
  2. Ureterovesical junction obstructionmay occur as a result of ureteroceles, primary megaureters, or abnormal insertion of the ureter into the bladder.
  3. Bladder outlet obstructionmay occur as a result of posterior urethral valves in males, polyps, or 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.
  5. Acquired obstruction

may occur as the result of renal calculi (see section XII), tumors, or strictures.

  1. Renal Abnormalities
  2. Renal agenesisoccurs 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).
  3. Unilateral renal agenesisoccurs in 0.1–0.2% of children.
  4. Bilateral renal agenesisis very rare. Infants die in the perinatal period secondary to associated pulmonary hypoplasia.
  5. Renal dysplasiais much more common than renal agenesis.
  6. Pathologically, renal dysplasia is associated with altered structural organization of the kidney, ranging in severity from mild to severe.
  7. Functionally, renal dysplasia is associated with concentrating defects, renal tubular acidosis, and varying degrees of renal insufficiency.
  8. Patients with relatively mild renal dysplasia and its associated renal functional abnormalities at birth may temporarily improve in later infancy and childhood, only to deteriorate in late childhood or adolescence.

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  1. Severe renal dysplasia results in a nonfunctional kidney.
  2. The most common abdominal mass discovered in newborns is the multicystic dysplastic kidney, which is usually associated with an atretic ureter.
  3. If bilateral and severe, multicystic dysplastic kidneys are incompatible with life. These infants are usually born with the stigmata of Potter's syndrome (see Chapter 5, section III.E.1).
  4. Other structural abnormalitiesinclude 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.
  5. Vesicoureteral Reflux (VUR)
  6. Definition.VUR is defined as urine refluxing from the urinary bladder into the ureters and the renal collecting system.
  7. Epidemiology
  8. Approximately 0.5% of healthy infants have some degree of VUR.
  9. VUR is identified in 30–50% of infants and young children with UTIs.
  10. Etiology
  11. VURis caused by abnormalities of the ureterovesical junction, most commonly a short submucosal tunnel in which the ureter inserts through the bladder wall.
  12. VUR has autosomal dominant inheritancewith variable expression.
  13. Classification.VUR is graded from grade 1 to grade 5 (Figure 11-4).
  14. Clinical features
  15. Most children with lower grades of VUR eventually have spontaneous resolution of the reflux.
  16. VUR may predispose to episodes of pyelonephritis, and severe pyelonephritis in turn may lead to renal scarring, especially in infants and young children.
  17. Reflux nephropathyis the pathologic entity resulting from severe VUR. This may lead to ESRD and hypertension. Kidneys show segmental scars, contraction, and interstitial nephritis.
  18. 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.
  19. Management
  20. Low-dose prophylactic antibioticsare prescribed to reduce the incidence of UTI until the child outgrows the VUR.
  21. Children with grade 4 or 5 reflux should be referred to a pediatric urologist for consideration of surgical reimplantation of the ureters.

XII. Urolithiasis

  1. Epidemiology

Renal stones are uncommon in children, and predisposing metabolic disorders should be sought in any child presenting with urinary calculi.

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Figure 11-4. Classification of vesicoureteral reflux.

  1. 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. Hyperoxaluria, which may be inherited or secondary to enteric malabsorption (e.g., inflammatory bowel disease)

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  1. Distal RTA
  2. Hyperuricosuria, which may occur during the treatment of leukemia or lymphoma, with Lesch-Nyhan syndrome, or with primary gout
  3. Cystinuria, which is an autosomal recessivedisorder that may lead to radiopaque renal stones
  4. UTI, especially with Proteus mirabilis
  5. Hyperparathyroidism
  6. Clinical features

Clinical findings include flank or abdominal pain, gross or microscopic hematuria, or symptoms of cystitis or pyelonephritis.

  1. 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 testingshould include electrolytes, BUN, creatinine, calcium, phosphorus, parathyroid hormone (PTH) level, uric acid level, and venous blood gas to rule out RTA.
  2. Urine testingshould 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 may also be necessary for 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.
  5. Management

Treatment is aimed first at hydration and the relief of any obstruction, treatment of any associated UTI, and then specific therapy on the basis of the underlying predisposing cause of the urolithiasis.

XIII. Urinary Tract Infection (UTI)

  1. Epidemiology

UTI is one of the most common bacterial infections in children.

  1. Incidenceof 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 boysas compared with boys who are circumcised.
  4. Etiology

The vast majority of UTIs are caused by enteric bacteria, especially E. coli. Other pathogens include KlebsiellaPseudomonasStaphylococcus saprophyticus (especially in adolescent females), Serratia, Proteus (associated with a high urinary pH), and Enterococcus.

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  1. Pathogenesis
  2. Most bacteria enter the urinary tract by ascendingthrough the urethra.
  3. Bacterial properties that promote the adherence of bacteria to the urothelium increase the likelihood of UTI.
  4. 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 childrenwho 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.
  5. Diagnosis and Evaluation
  6. Diagnosis depends on the proper collection of the urine specimen.
  7. 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 notfor culture.
  8. In older childrenwho can void on command, a careful “clean-catch” urine sample is adequate for culture.
  9. 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.
  10. Urinalysis findings suggestive of UTIinclude the presence of leukocytes on microscopy (> 5–10 WBCs/HPF) and a positive nitrite or leukocyte esterase on dipstick.
  11. Urine cultureremains the “gold standard” for diagnosis. Significant colony counts depend on the culture method:
  12. Any growth on urine collected by suprapubic aspiration
  13. ≥ 10, 000 colonies in samples obtained by sterile urethral catheterization
  14. ≥ 50, 000–100, 000 colonies of a single organism in urine collected by clean-catch technique
  15. Imaging
  16. Imaging is indicated in selected children with UTI because children with UTI have a significant incidence of structural abnormalities of the urinary tract (e.g., vesicoureteral reflux).
  17. All children with pyelonephritis, all children with recurrent UTI, all males, and all girls younger than 4 years of age with cystitis should

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have an imaging evaluation, which should include a renal ultrasound and a VCUG.

  1. Management
  2. Empiric antibiotic therapyshould be started in symptomatic patients with a suspicious urinalysis while culture results are pending. Commonly used oral antibiotics include trimethoprim–sulfamethoxazole or cephalexin.
  3. Neonateswith UTIs are admitted to the hospital for initial intravenous management, which commonly includes ampicillin and gentamicin.
  4. Toxic-appearing childrenwith high fever and children with dehydration should also be admitted to the hospital for initial intravenous antibiotics and hydration. Oral antibiotics are started once the child has shown initial improvement.
  5. Duration of treatment for cystitis is usually 7–10 days, and for pyelonephritis, 14 days.
  6. Because the risk of renal scarring after pyelonephritis is greatest in infants, they should receive low-dose prophylactic antibiotics for at least 3 months after an episode of pyelonephritis.

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Review Questions and Answers

  1. A 3-week-old uncircumcised male infant presents with a 2-day history of very poor feeding. He now takes only 1 ounce of formula every 3 hours, instead of the usual 2–3 ounces. 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 this boy developing a UTI is greater than that of a girl, but after infancy, he has the same risk as a 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.

  1. 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).

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  1. 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.

  1. 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 1+ 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 normally occurs.

  1. 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 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.

  1. 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.

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  1. 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

  1. A 9-month-old female infant 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). Which of the following statements regarding VUR is correct?

(A). Inheritance of VUR is 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 only grade 2 VUR, she does not require low-dose prophylactic antibiotics; the risk of subsequent urinary tract infection is low.

  1. 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 101°F (38.3°C). 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 1, 000 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 fever above 38°C (0° Fahrenheit).

(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.

  1. 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

  1. 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

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

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.

(A). Autosomal dominant

(B). Autosomal recessive

(C). Sporadic

(D). X-linked dominant

(E). X-linked recessive

  1. 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.

(A). Autosomal dominant

(B). Autosomal recessive

(C). Sporadic

(D). X-linked dominant

(E). X-linked recessive

  1. A 15-year-old boy who has mild hearing loss, mild hypertension, hematuria, and proteinuria.

(A). Autosomal dominant

(B). Autosomal recessive

(C). Sporadic

(D). X-linked dominant

(E). X-linked recessive

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Answers and Explanations

  1. The answer is D[XIII.A, XIII.E.1, XIII.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 highly 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 11-2]. 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 co-transport 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's 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[IV.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 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.

P.358

  1. The answer is D[V.A, V.B, V.E, V.G.5]. Nephrotic syndrome in children is defined as heavy proteinuria (>50 mg/kg/24 hr), 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. 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 those who do not respond to initial management with corticosteroids.
  2. The answer is E[VI.C.3]. There are two subtypes of HUS, a shiga toxin-associated form (most common form in childhood) and an atypical form caused by medications or genetic inheritance. Shiga toxin-associated HUS occurs as a result of intestinal infection with a toxin-producing bacteria, most commonly Escherichia coli0157: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 not indicated and may actually increase the likelihood that a patient will go on to develop HUS.
  3. The answer is C[IV.F.2]. This patient's clinical presentation and ethnicity are consistent with IgA nephropathy (Berger's 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.
  4. The answer is D[XI.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. 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. Patients with VUR of any grade are treated with low-dose prophylactic antibiotics to decrease the risk of urinary tract infection.
  5. The answer is E[I.B, 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 1, 500 mL/m2/day. Fever will result in increased insensible losses, and maintenance fluids should be increased by 12% for every degree of fever 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.
  6. The answer is E[Figure 11-1 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) does 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 unusual in a neonate. Similarly, although sickle cell disease also causes hematuria, it is an uncommon presentation in a neonate. Hypercalciuria is a common cause of hematuria; however, a flank mass would not be a presenting sign.

P.359

 

  1. 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.

12–14. The answers are B, A, and D, respectively [VII.D, VII.E, and VII.B]. Infantile polycystic kidney disease 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 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 is also associated with cerebral aneurysms and early death. Alport's syndrome is inherited in multiple patterns, but the X-linked dominant form is by far the most common. Alport's syndrome is characterized by renal manifestations, including hypertension and hematuria, as well as renal failure in males; hearing loss; and ocular abnormalities of the lens and retina.