A 43-year-old man comes to the office due to worsening pedal edema for the last several weeks. He also has had fatigue but no dyspnea, orthopnea, or chest pain. The patient was diagnosed with HIV during a screening 5 years ago. He refused treatment in the past but has been taking antiretroviral therapy and prophylactic trimethoprim-sulfamethoxazole after being hospitalized for Pneumocystis pneumonia 4 months ago. He does not use tobacco, alcohol, or illicit drugs. Temperature is 36.7 C (98.1 F), blood pressure is 140/86 mm Hg, and respirations are 16/min. Physical examination shows normal heart and lung sounds, a nontender abdomen with no organomegaly, and no rashes. There is 2+ pitting edema on the bilateral lower extremities. Laboratory results are as follows: Urinalysis reveals 3+ proteinuria but no other abnormalities. Serum creatinine was normal at hospital discharge 4 months ago, and CD4 cell count was 220/mm³ a month ago. Which of the following is the most likely cause of this patient's current condition?

Question

Quizplus · Accepted Answer

This patient with previously untreated HIV infection has edema, acute kidney injury, and proteinuria, likely due to HIV-associated nephropathy (HIVAN). HIVAN is thought to be caused by direct infection of the renal tubular and glomerular cells by the HIV virus. Patients with advanced HIV (ie, low CD4 cell count, high viral load) or AIDS are particularly susceptible, although HIVAN may occur in patients with normal CD4 counts. It is especially prevalent in patients of sub-Saharan African descent, possibly due to the presence of an apolipoprotein L1 (APOL1) gene variant that is thought to confer resistance to trypanosomiasis but may increase susceptibility to HIVAN. HIVAN can develop relatively quickly and typically presents with heavy proteinuria and rapidly progressive renal failure. Edema, hematuria, and hypertension may also occur. The diagnosis is confirmed with renal biopsy that demonstrates collapsing focal segmental glomerulosclerosis; tubuloreticular inclusions are usually visible on electron microscopy. Antiretroviral therapy (ART) may help kidney recovery and should be initiated in patients who develop HIVAN and are not already on therapy; therefore, although this patient's kidney dysfunction developed following ART initiation, it is unlikely due to ART. ACE inhibitors are used in patients with proteinuria and hypertension. The prognosis for HIVAN is poor and many patients develop end-stage renal disease even with therapy. (Choice A) BK virus-induced nephropathy causes progressive renal failure but is characterized by an interstitial nephritis with hematuria, pyuria, and white blood cell casts, not marked proteinuria. It occurs more commonly in patients who have received renal transplants. (Choice B) Crystal-induced tubular dysfunction can occur with sulfamethoxazole-containing antibiotics, but it typically presents with hematuria, pyuria, and crystalluria; flank pain may also occur. Heavy proteinuria would be atypical. (Choice C) Interstitial nephritis commonly occurs with antibiotics (eg, trimethoprim-sulfamethoxazole) and certain antiretrovirals (eg, indinavir), but typically presents with fever, rash, eosinophilia, and pyuria with white cell casts. Isolated proteinuria is unexpected. (Choice E) Primary membranous nephropathy causes nephrotic syndrome with proteinuria; however, it typically causes a slowly progressive chronic kidney disease and most patients have normal creatinine on presentation. Secondary membranous nephropathy typically occurs with Hepatitis B and C, not HIV. Educational objective: HIV-associated nephropathy is thought to be caused by direct infection of the renal epithelial cells by HIV and typically presents with heavy proteinuria, rapidly progressive renal failure, and edema. It is most common in patients of sub-Saharan African descent with advanced HIV infection.

A 43-Year-Old Man Comes to the Office Due to Worsening