MKSAP: 25-year-old man with swelling of the feet and legs

MKSAP: 25 year old man with swelling of the feet and legsTest your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 25-year-old man is evaluated in the emergency department for swelling of the feet and legs. He has a 5-year history of HIV infection for which he has refused treatment.

On physical examination, temperature is normal, blood pressure is 128/74 mm Hg, pulse rate is 88/min, and respiration rate is 12/min. BMI is 23. Cardiopulmonary examination is normal. Abdominal examination is normal. There is 2+ presacral and 3+ bilateral lower-extremity edema.

Laboratory studies:

CD4 cell count 140/µL
HIV RNA viral load 120,000 copies/mL
Hepatitis B surface antigen (HBsAg) Negative
Antibodies to hepatitis C virus (anti-HCV) Negative
VDRL Negative
Antinuclear antibodies Negative
Blood urea nitrogen 18 mg/dL (6.4 mmol/L)
Serum creatinine 1.1 mg/dL (97.2 µmol/L)
Urinalysis 4+ protein; 2 to 3 erythrocytes/hpf; 1 to 2 leukocytes/hpf
Urine protein-creatinine ratio 12 mg/mg

Kidney ultrasound reveals bilaterally enlarged kidneys with patchy areas of increased density. The renal veins are patent. Kidney biopsy is performed, and results are pending.

Which of the following is the most likely diagnosis?

A) Collapsing focal segmental glomerulosclerosis
B) IgA nephropathy
C) Membranous nephropathy
D) Postinfectious glomerulonephritis

MKSAP Answer and Critique

The correct answer is A) Collapsing focal segmental glomerulosclerosis. This item is available to MKSAP 15 subscribers as item 4 in the Nephrology section. More information about MKSAP 15 is available online.

This patient most likely has HIV-associated nephropathy (HIVAN) caused by collapsing focal segmental glomerulosclerosis (FSGS). Collapsing FSGS is the most common kidney disease associated with HIV infection and predominantly affects black patients. HIVAN is classically associated with a low CD4 cell count and high HIV RNA viral load but may manifest differently in patients whose HIV infection is well controlled with highly active antiretroviral therapy (HAART) or who have an acute retroviral syndrome. Collapsing FSGS is characterized by hypoalbuminemia, edema, heavy proteinuria, and minimal erythrocytes and leukocytes in the urine. Most patients have a normal blood pressure.

HAART is considered the treatment of choice in patients with HIVAN, and protease inhibitor–based HAART regimens have been shown to reduce the progression of kidney disease in this setting; adding corticosteroids to this therapy may provide further benefit. In addition, treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker helps to decrease urine protein excretion.

Postinfectious glomerulonephritis and IgA nephropathy are possible kidney complications of HIV infection. Postinfectious glomerulonephritis can potentially develop after numerous bacterial infections, which frequently occur in patients with HIV infection. IgA nephropathy may be the result of IgA interaction with HIV antigens but would manifest as minimal proteinuria and an active urine sediment, which is not compatible with this patient’s presentation.

Membranous nephropathy can cause the nephrotic syndrome in patients with HIV infection. Membranous nephropathy is most commonly associated with HIV infection–related complications such as hepatitis B or C virus infection or syphilis and may be associated with renal vein thrombosis, which are absent in this patient. This condition also is associated with systemic lupus erythematosus and the use of certain drugs, but these circumstances are unlikely in a patient who takes no medications and has a negative antinuclear antibody assay.

Key Point

  • The most common cause of HIV-associated nephropathy is collapsing focal segmental glomerulosclerosis, which is characterized by massive proteinuria.

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