Case Files Pediatrics, (LANGE Case Files) 4th Ed.

CASE 29

A 14-year-old Hispanic male presents with a 3-day complaint of “brown urine.” He has been your patient since birth and has experienced no major illnesses or injuries, is active in band and cross-country, and denies drug use or sexual activity. Two weeks ago he had 2 days of fever and a sore throat, but he improved spontaneously and has been well since. His review of systems is remarkable only for his slightly puffy eyes, which he attributes to late-night studying for final examinations. On physical examination he is afebrile, his blood pressure is 135/90 mm Hg, he is active and nontoxic in appearance, and he has some periorbital edema. The urine dipstick has a specific gravity of 1.035 and contains 2+ blood and 2+ protein. You spin the urine, resuspend the sediment, and identify red blood cell casts under the microscope.

Image What is the most likely cause of this patient’s hematuria?

Image What laboratory tests would support this diagnosis?

Image What is the prognosis of this condition?

ANSWERS TO CASE 29: Acute Poststreptococcal Glomerulonephritis

Summary: A healthy adolescent male with a preceding pharyngitis has periorbital edema and mild hypertension, and has developed tea-colored urine that on microscopy reveals red blood cells.

• Most likely diagnosis: Acute poststreptococcal glomerulonephritis (APSGN).

• Laboratory studies: C3 (low in 90% of cases), C4 (usually normal); antistreptolysin-O (ASO) enzyme antibodies and antideoxyribonuclease B (anti-DNase B) antibodies provide evidence of recent streptococcal infection.

• Prognosis: Excellent; 95% to 98% of affected children recover completely.

ANALYSIS

Objectives

1. Recognize the typical presentation of APSGN.

2. Know the different diagnostic possibilities for a patient with dark urine.

3. Discuss appropriate follow-up care for the patient with APSGN.

Considerations

This patient is otherwise healthy, had pharyngitis, and now has hematuria, proteinuria, edema, and hypertension. Although APSGN is likely, other possibilities must be considered. Strenuous activity can cause rhabdomyolysis and dark urine, but patients with these conditions often will have muscle aches, fatigue, nausea and vomiting, and fever. Immunoglobulin A (Berger) nephropathy is characterized by recurrent painless hematuria, usually preceded by an upper respiratory tract infection. Henoch-Schönlein purpura (HSP) is a relatively common cause of nephritis in pediatrics, but most cases occur in younger children, peaking in incidence between 4 and 5 years of age. Lupus nephritis (systemic lupus erythematosus [SLE]) can present as described and is considered if the hematuria does not resolve or if the C3 level does not normalize in 6 to 12 weeks.

APPROACH TO:

Acute Poststreptococcal Glomerulonephritis

DEFINITIONS

GLOMERULONEPHRITIS: Glomerular inflammation resulting in the triad of hematuria, proteinuria, and hypertension.

RED CELL CASTS: Injured glomeruli have increased permeability and leak red cells and proteins into the proximal convoluted tubule; the material subsequently clumps in the distal convoluted tubule and in the collecting ducts. When passed, these cell clumps retain the shape of the tubule in the urine. Red cell casts are markers for glomerular injury.

CLINICAL APPROACH

Acute poststreptococcal glomerulonephritis (APSGN) is the most common of the postinfectious nephritides, comprising 80% to 90% of cases. Other bacteria, viruses, parasites, and fungi also have been implicated. Males are more commonly affected; it is most common in children between the ages of 5 and 15 years and is rare in toddlers and infants. The group A β-hemolytic Streptococcus (GABHS) infection can be in the form of either pharyngitis (“strep throat”) or a superficial skin lesion (impetigo). Not all GABHS infections result in APSGN; certain GABHS strains are “nephritogenic” and are more likely to result in APSGN. Rheumatic fever only rarely occurs concomitantly with APSGN. Antibiotic use during the initial GABHS infection may reduce the subsequent rheumatic fever risk,yet has not been shown to prevent APSGN. The nephritis risk after infection with a nephritogenic strain of GABHS remains 10% to 15%.

Generally the interval between GABHS pharyngitis and APSGN is 1 to 2 weeks; the interval between GABHS impetigo and APSGN is 3 to 6 weeks. Symptom onset is abrupt. Although almost all patients have microscopic hematuria, only 30% to 50% develop gross hematuria. In addition, 85% present with edema and 60% to 80% develop hypertension.

The most important laboratory test in patients with APSGN is measurement of serum C3 and C4 levels. C3 is low in 90% of APSGN cases, whereas C4 usually is normal. If both levels are low, an alternate diagnosis is considered. Urinalysis typically reveals high specific gravity, low pH, hematuria, proteinuria, and red cell casts. Documentation of a recent streptococcal infection is helpful; serum markers include the presence of ASO enzyme antibodies and anti-DNase B antibodies. ASO antibodies are found in 80% of children with recent GABHS pharyngitis but in less than 50% of children with recent GABHS skin infection. ASO titers are positive in 16% to 18% of normal children. Anti-DNase B antibodies assays are more reliable; they are present in almost all patients after GABHS pharyngitis and in the majority of patients after GABHS skin infection. Antibodies to other streptococcal antigens (nicotamide adenosine dinucleotide glycohydrolase [NADase], hyaluronidase, and streptokinase) may also be assayed. Renal biopsy is no longer routine. Treatment is generally supportive. Fluid balance is crucial; diuretics, fluid restriction, or both may be necessary. Sodium and potassium intake may require restriction. Hypertension usually is easily controlled with calcium-channel blockers. Strict bed rest and corticosteroid medications are not helpful. Dialysis is rarely required.

Resolution usually is rapid and complete. The edema resolves in 5 to 10 days, and patients usually are normotensive within 3 weeks. C3 levels usually normalize in 2 to 3 months; a persistently low C3 level is uncommon and suggests an alternate diagnosis. Microscopic hematuria may persist for 1 to 2 years.

COMPREHENSION QUESTIONS

29.1 A 16-year-old adolescent boy complains of intermittent cola-colored urine of several years’ duration, usually when he has a “cold.” He is otherwise well and has no medical complaints. When the dark-colored urine is present, he has no dysuria. None of his family members has similar complaints or renal disease. On physical examination he is normotensive and appears healthy. Which of the following is the most likely cause of his intermittent hematuria?

A. Acute poststreptococcal glomerulonephritis

B. Henoch-Schönlein purpura nephritis

C. IgA nephropathy

D. Recurrent kidney stones

E. Rapidly progressive glomerulonephritis

29.2 The parents of a healthy 12-year-old girl bring her to you for a physical examination required for summer camp. They have no complaints, and the girl denies any problems. Her last menses was normal 2 weeks prior. The camp requires a urine screen. To your surprise, the clean-catch urine screen has significant hematuria. Red cell casts are noted. You tell the findings to the parents, and they respond that “everyone on dad’s side of the family has blood in their urine and they are all doing well.” The family history is negative for deafness and for renal failure. Microscopy of renal tissue from this patient or from her father will most likely reveal which of the following?

A. Endothelial cell swelling and fibrin in the subendothelial space

B. Immune complex deposition in the mesangium

C. Large numbers of crescentic glomeruli

D. Renal cell carcinoma

E. Thinning of the basement membrane

29.3 A 17-year-old adolescent female has joint tenderness for 2 months; the pain has affected her summer job as a lifeguard. In the morning, she awakens with bilateral knee pain and swelling, and right hand pain. The pain eases during the day but never completely resolves. Nonsteroidal anti-inflammatory drugs help slightly. She also wants a good “face cream” because “her job has worsened her acne.” On physical examination you notice facial erythema on the cheeks and nasolabial folds. She has several oral ulcers that she calls cold sores and bilateral knee effusions, and her right distal interphalangeal joints on her hand are swollen and tender. Her liver is palpable 3 cm below the costal margin. She has microscopic hematuria and proteinuria. Which of the following is the most likely cause of this young woman’s arthritis?

A. Juvenile rheumatoid arthritis

B. Lyme disease

C. Osteoarthritis

D. Postinfectious arthritis

E. Systemic lupus erythematosus

29.4 You are not surprised to see one of your most challenging patients, a 16-year-old adolescent girl who has been seen several times per week over the last 2 months complaining of cough, occasional hemoptysis, malaise, and intermittent low-grade fever. Thus far you have identified a microcytic, hypochromic anemia for which she has been taking iron (without response) and migratory patchy infiltrates on chest radiograph that seem unaffected by antibiotic treatment. She has no tuberculosis (TB) exposure risks, and her TB skin test was negative. Today she also complains of facial edema and tea-colored urine. You suddenly realize her symptoms can be grouped as which of the following syndromes?

A. Alport syndrome

B. Denys-Drash syndrome

C. Goodpasture syndrome

D. Hemolytic-uremic syndrome

E. Nephrotic syndrome

ANSWERS

29.1 C. Recurrent painless gross hematuria, frequently associated with an upper respiratory tract infection, is typical of IgA nephropathy. These patients may develop chronic renal disease over decades. If proteinuria, hypertension, or impaired renal function were found, a biopsy would be necessary. The other options are not consistent with the asymptomatic, intermittent nature of this patient’s problem.

29.2 E. This history is consistent with benign familial hematuria, an autosomal dominant condition that causes either persistent or intermittent hematuria without progression to chronic renal failure. Biopsy reveals a thin basement membrane; in some cases the biopsy is normal. Immune complex deposition with immunoglobulin (Ig) A in the mesangium is seen in HSP and IgA nephropathy; endothelial cell swelling with fibrin deposition is seen in hemolytic-uremic syndrome, and crescentic glomeruli are seen in rapidly progressive glomerulonephritis.

29.3 E. Systemic lupus erythematosus affects more women than men, and nephritis is a common presenting feature. Her rash, photosensitivity, oral ulcers, hepatomegaly, arthritis, and nephritis combine to make this a likely diagnosis. A positive antinuclear antibody test and low C3 and C4 levels would help to confirm the diagnosis.

29.4 C. Goodpasture syndrome is the clinical diagnosis when patients exhibit nephritis and pulmonary hemorrhage. It can be caused by a number of conditions, including SLE and HSP. Alport syndrome is a genetic defect in collagen synthesis that leads to abnormal basement membrane formation; patients will develop hematuria, proteinuria, and renal failure. Denys-Drash syndrome is a group of findings composed of Wilms tumor, gonadal dysgenesis, and nephropathy.


CLINICAL PEARLS

Image Poststreptococcal glomerulonephritis is the most common postinfectious nephritis and has a good prognosis.

Image Confirming the diagnosis of APSGN requires evidence of invasive streptococcal infection such as an elevated anti-DNase B titer.


REFERENCES

Barron CS. Henoch-Schönlein purpura (anaphylactoid purpura). In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA, eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:810-812.

Brewer ED. Glomerulonephritis and nephrotic syndrome. In: McMillan JA, Feigin RD, DeAngelis CD, Jones MD, eds. Oski’s Pediatrics: Principles and Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:1854-1862.

Eddy AA. Glomerular diseases. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA, eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:1710-1722.

Kashtan CE. Denys-Drash syndrome. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA, eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:1731.

Lum GM. Glomerulonephritis. In: Hay WW, Levin MJ, Sondheimer JM, Deterding RR, eds. Current Diagnosis & Treatment Pediatrics. 20th ed. New York, NY: McGraw-Hill; 2011:679-681.

Pan CG, Avner ED. Acute poststreptococcal glomerulonephritis. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier; 2011:1783-1785.

Pan CG, Avner ED. Isolated glomerular diseases with recurrent gross hematuria. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, Behrman RE, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier; 2011:1781-1783.

Silverman ED. Systemic lupus erythematosus. In: Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA, eds. Rudolph’s Pediatrics. 22nd ed. New York, NY: McGraw-Hill; 2011:814-818.