Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 25-year-old man is evaluated for dark-colored urine for 2 days, swelling of the face and hands for 1 day, and severe headaches this morning. He reports having an upper respiratory tract infection 1 week ago with fever, sore throat, and swollen glands, but had otherwise felt well. Medical history is otherwise unremarkable, and he takes no medications.

On physical examination, temperature is 37.2 °C (99.0 °F), blood pressure is 180/90 mm Hg, pulse rate is 88/min, and respiration rate is 14/min. Cardiopulmonary and abdominal examinations are normal. No skin rash or arthritis is present. There is bilateral lower extremity edema to the mid shins.

Laboratory studies:

Albumin	3.3 g/dL (33 g/L)
C3	Low
C4	Normal
Creatinine	1.4 mg/dL (124 µmol/L)
Antistreptolysin O antibodies	Elevated
Urinalysis	3+ blood; 2+ protein; too numerous to count erythrocytes/hpf; 10-15 leukocytes/hpf; numerous erythrocyte casts
Urine protein-creatinine ratio	1900 mg/g
Rapid streptococcal antigen test	Positive

Which of the following is the most likely diagnosis?

A. IgA nephropathy
B. Infection-related glomerulonephritis
C. Lupus nephritis
D. Small-vessel vasculitis

MKSAP Answer and Critique

The correct answer is B. Infection-related glomerulonephritis.

This patient likely has infection-related glomerulonephritis (IRGN) following a streptococcal infection. Supportive evidence includes preceding symptoms of an upper respiratory tract infection suggestive of streptococci (rapid streptococcal antigen test is positive and antistreptolysin O antibodies are elevated), followed by the nephritic syndrome in 1 week, and low C3 levels with normal C4 levels (suggesting an alternative pathway of complement activation, which is typical of IRGN). Most patients will show spontaneous resolution of nephritis with conservative management (antibiotics, blood pressure management, and diuretics).

IgA nephropathy (IgAN) is the most common form of glomerulonephritis. Asymptomatic microscopic hematuria with or without proteinuria is the most common presentation of IgAN, and episodic gross hematuria following an upper respiratory tract infection is a classic presentation. Kidney manifestations usually occur concomitantly with the respiratory infection in IgAN (“synpharyngitic” nephritis), as opposed to the typical 7- to 10-day latent period with IRGN. Moreover, complement levels are typically normal in IgAN, whereas C3 is typically low and C4 is normal in IRGN.

Lupus nephritis may occasionally be precipitated by infections. Patients with lupus typically experience systemic manifestations such as rash and arthritis, although kidney-limited disease is sometimes seen. Both C3 and C4 complement levels are depressed in this condition due to the classical pathway of complement being activated. In IRGN, C3 is typically depleted, with normal levels of C4 due to activation of the alternative pathway of complement.

Small-vessel vasculitis is also associated with glomerulonephritis. However, there are frequently other clinical findings of vasculitis present, and complement levels are typically normal.

Key Point

• Poststreptococcal glomerulonephritis is characterized by preceding symptoms of an upper respiratory tract infection suggestive of streptococci, followed by the nephritic syndrome and low C3 levels with normal C4 levels.

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