A 7-year-old boy is brought to the office due to lethargy and dark urine. The patient has had no abdominal pain, fever, dysuria, urinary frequency, or urgency. Temperature is 37.4 C (99.3 F). Physical examination shows periorbital swelling and mild pedal edema. Cardiopulmonary examination reveals no abnormalities. The remainder of the examination is unremarkable. Laboratory results are as follows: The serum C3 concentration is low, and the C4 concentration is normal. Which of the following is the most likely diagnosis in this patient?

Question

A 7-year-old boy is brought to the office due to lethargy and dark urine.  The patient has had no abdominal pain, fever, dysuria, urinary frequency, or urgency.  Temperature is 37.4 C (99.3 F).  Physical examination shows periorbital swelling and mild pedal edema.  Cardiopulmonary examination reveals no abnormalities.  The remainder of the examination is unremarkable.  Laboratory results are as follows:  The serum C3 concentration is low, and the C4 concentration is normal.  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec25c8_d72c_ffbd_bc81_53cf2c685d01_MD0003_00 Nephritic syndromes (ie, glomerulonephritis) are characterized by glomerular inflammation, which results in acute-onset hematuria and red blood cell (RBC) casts on urinalysis. Additional clinical features may include mild or moderate proteinuria (eg, 1+ protein on urinalysis), acute kidney injury, edema (eg, periorbital swelling), and hypertension. In children, the most common cause of nephritic syndrome is acute poststreptococcal glomerulonephritis (APSGN), which develops several weeks after group A Streptococcus (GAS) infection (eg, pharyngitis, impetigo). APSGN occurs when antigens on nephritogenic strains of GAS form IgG and/or IgM immune complexes that are then deposited between the glomerular basement membrane and the mesangium (ie, subepithelial). The IgG and IgM immune complexes have high complement-fixing activity, leading to complement system activation and accumulation of complement component C3 in the glomerular deposits, causing low serum levels of C3 and CH₅₀. This results in a leukocytic inflammation that thickens the glomerular basement membrane, leading to decreased glomerular filtration (eg, elevated serum creatinine) and fluid retention (eg, edema), and disrupts the epithelial podocytes, causing increased glomerular damage and permeability (eg, nephritic syndrome). ₅₀ Treatment of APSGN is supportive (eg, diuresis, blood pressure control) because symptoms typically resolve within weeks; however, laboratory abnormalities may take months to normalize. (Choice A) Focal segmental glomerulosclerosis (FSGS) may present with edema and hematuria. However, because FSGS is a form of nephrotic syndrome, patients typically have nephrotic-range proteinuria (eg, 3+ protein on urinalysis) and no RBC casts, making this diagnosis unlikely. (Choice B) Patients with hemolytic uremic syndrome may have acute kidney injury, hematuria, and low C3 levels. However, they usually have clinical features of microangiopathic hemolytic anemia (hemoglobin <8 g/dL), which is not seen in this patient. In addition, RBC casts are typically not seen on urinalysis. (Choice C) Like APSGN, IgA nephropathy can present with nephritic syndrome; however, IgA nephropathy is typically associated with normal serum complement levels, likely due to the weak complement-fixing activity of IgA compared to that of IgG and IgM. (Choice D) Minimal change disease, a common cause of nephrotic syndrome in children age <10, can present with fatigue and edema. However, patients typically have nephrotic-range proteinuria and no associated hematuria or RBC casts. Educational objective: Acute poststreptococcal glomerulonephritis causes the formation of immune complex deposits, activation of the complement system, and subsequent damage within the glomerulus. Therefore, symptomatic patients typically have hematuria, hypertension, and edema. In addition, complement component C3 and total complement (CH₅₀) are low; C4 is most often normal or slightly low. ₅₀ References: Post-streptococcal glomerulonephritis. (http://www.ncbi.nlm.nih.gov/pubmed/26866231) IgA nephropathy. (http://www.ncbi.nlm.nih.gov/pubmed/28159829)

A 7-Year-Old Boy Is Brought to the Office Due to Lethargy