Pediatric Examination and Board Review (223 page)

2.
Which is the least common cause of isolated microscopic hematuria?

(A) benign familial hematuria/thin basement membrane disease

(B) idiopathic hypercalciuria

(C) Alport syndrome

(D) IgA nephropathy

(E) exercise

3.
If the urinary calcium/creatinine ratio was 0.45 and reconfirmed, the patient should be

(A) encouraged to drink more than 2 L of fluids in 24 hours

(B) placed on a low-sodium, normal-calcium diet

(C) treated with thiazides

(D) none of the above

(E) all of the above

4.
Gross hematuria persisted for 7 days. A renal ultrasound was ordered that showed enlargement of both kidneys with multiple cysts bilaterally consistent with autosomal dominant polycystic kidney disease (ADPKD). The next test that should be ordered is

(A) magnetic resonance angiography (MRA) of brain

(B) US of abdomen

(C) VCUG

(D) genetic testing for PKD1 and PKD2

(E) sweat chloride test

5.
This 15-year-old boy with ADPKD may demonstrate which of these clinical manifestations during childhood?

(A) pain

(B) hematuria

(C) hypertension

(D) renal insufficiency

(E) A, B, and C

ANSWERS

1.
(A)
There are many causes of microscopic hematuria without significant proteinuria, some benign and some serious. Truly asymptomatic microscopic hematuria is present in 3-4% of school-age children, most of whom have no significant clinical disease. Thus the most important part of the initial evaluation is a careful history. The history of present illness should confirm that the patient is truly asymptomatic—that there is no history of trauma, lower urinary tract symptoms, no edema, or no history of granular urine. The past medical history is important to exclude a relevant illness such as lupus or sickle cell disease. Also, the family history is important. Inquiries should be made about hematuria, renal failure, deafness, and nephrolithiasis. A physical examination is important, including a blood pressure measurement. Because some causes are transient, as in recovering postinfectious GN or after exercise, it is important to make sure the finding persists over time and to check for hematuria when the patient has not been exercising. When hematuria is persistent, a CT is occasionally done; an US is usually done to rule out hydronephrosis, obstruction, stone, and renal malignancy. A calcium-to-creatinine spot ratio is usually sent, and if history, imaging, or this ratio is suggestive of nephrolithiasis, a more complete workup is usually done, as indicated. A biopsy is usually reserved for significant or worsening proteinuria or renal impairment.

2.
(C)
Alport syndrome is a rare condition, usually X-linked, and thus worse in males than carrier females. It consists of hereditary nephritis accompanied by neurosensory hearing loss. Benign familial hematuria is a common syndrome associated with hematuria that is diagnosed by screening first-degree relatives. On biopsy, the basement membrane of the glomerular filtration barrier is thinned. Increasing evidence indicates some of these patients are heterozygous carriers for collagen defects that are found in autosomal recessive Alport syndrome. Idiopathic hypercalciuria is also a common cause of hematuria. It is diagnosed if the urinary calcium-to-creatinine is more than 0.21. IgA nephropathy is a strong consideration. It is often characterized by 1-2 days of gross hematuria during an upper respiratory tract infection. Between episodes of gross hematuria there is microscopic hematuria, and occasionally proteinuria or renal insufficiency. Diagnosis is made by renal biopsy showing deposition of IgA on immunofluorescence. After significant exercise, microscopic hematuria is often present.

3.
(D)
Idiopathic hypercalciuria is a common syndrome associated with microscopic hematuria in childhood. There is disagreement as to whether hypercalciuria leads to renal stones. Thus treatment is reserved for patients who have previously had nephrolithiasis, have calcifications on US, or patients with a strong family history of hypercalciuria and nephrolithiasis. Increased fluid intake, restricted sodium, ample intake of calcium (>1200 mg/day), and thiazide treatment are helpful in preventing recurrent nephrolithiasis. In adults, protein restriction is sometimes also recommended, but in children the need for growth must also be considered, and protein is not usually restricted.

4.
(B)
ADPKD occurs in 1 in 400-1000 live births. In ADPKD, renal involvement is characterized by cystic dilations in all parts of the nephron including Bowman space. In the early stages there may only be a few irregularly distributed macrocysts. Later, both kidneys are enlarged and large cysts are present in the cortex and medulla. Cysts in the liver, pancreas, and other organs are common in patients with ADPKD, but congenital hepatic fibrosis is rare. Cerebral vessel malformations have been described, and a ruptured cerebral aneurysm is the most serious complication of PKD. An MRA (or CTA) of the brain should be performed to exclude cerebral aneurysms in those at high risk (including previous rupture, warning symptoms, high-risk occupation or positive family history of aneurysm or bleed), but the role of screening all patients with ADPKD is currently unresolved. This is due to the risk of complications following elective aneurysm surgery and the high frequency of finding small aneurysms at low risk for rupture. A VCUG is not part of the workup for a patient with ADPKD unless there is a UTI or hydronephrosis. Genetic testing is now available that can find a molecular change in about 70% of affected patients because about 85% of patients with ADPKD have a mutation in the PKD1 locus, and the rest have a different defect in the PKD2 locus. Thus screening can be used for counseling, but it can be expensive and its role in children who are at risk is debatable because there can be adverse effects of a presymptomatic positive finding. A sweat chloride test is used to diagnose cystic fibrosis.

5.
(E)
Manifestations of disease such as pain, hematuria, and hypertension are associated with large or enlarging kidneys. The GFR does not deteriorate in this population of children. Renal insufficiency often develops in later decades with less than 2% of patients progressing to end-stage renal disease (ESRD) before age 40. However, 75% have ESRD by age 75. There is marked interfamilial heterogeneity and even intrafamilial variability regarding prognosis. Specific therapies are being evaluated, but typically blood pressure is well controlled usually with ACE inhibitors and receptor blockers.

S
UGGESTED
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EADING

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Jais PJ, Knebelmann B, Giatras I, et al. X-linked Alport syndrome: natural history in 195 families and genotype-phenotype correlations in males.
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Chapter 16

NEUROLOGY

CASE 131: A 6-YEAR-OLD GIRL WITH STARING SPELLS

The teacher of a 6-year-old African American girl refers her to your clinic for an evaluation of frequent episodes of staring. The episodes occur daily and are brief, lasting no more than 5-8 seconds. She typically has several events per day. Occasionally, when the children are playing during recess, the child will stop what she is doing and exhibit a blank facial expression. She often picks at her clothes during these episodes. Following the event, she resumes her activity. Her mother states that she has not noticed any of these particular spells but notes that the child frequently “daydreams” at home, during which she is unresponsive to verbal stimuli. The child was born at full term without complications. There is no history of bowel or bladder incontinence, headache, or emesis. The child states that she is unaware of the episodes, but believes there are times when she has missed things that have been said to her. She denies any aura. There is no history of febrile seizures, central nervous system (CNS) infections, or head trauma.

On reviewing her family history, you discover that the child has a maternal great-aunt with “terrible seizures” unresponsive to medications. Her mother recalls having similar “daydreaming episodes” as a child for which she was treated with medication until high school. There is a strong family history of depression.

On physical examination, she has a large café au lait spot on her back. On neurologic examination, she has normal intelligence. Her cranial nerve examination is unremarkable. She has normal strength in both the upper and lower extremities. Her deep tendon reflexes are symmetric at 2+ of 4. Her gait is normal.