A 43-year-old man comes to the office due to fatigue and worsening pedal edema over the past several weeks. The patient was diagnosed with advanced HIV infection and started on antiretroviral therapy 3 months ago. He also has a history of hypertension. Physical examination shows bilateral lower extremity pitting edema. Serum creatinine is elevated and serum phosphorus is decreased compared to test results 3 months ago. Urinalysis reveals moderate proteinuria and glucosuria. Renal biopsy shows cytoplasmic vacuolization in the proximal tubules accompanied by loss of brush border and basement membrane denudation. Intracytoplasmic eosinophilic inclusions are also seen in the proximal tubules. There are no significant interstitial inflammatory infiltrates, and the glomeruli appear normal. Which of the following is the most likely diagnosis in this patient?

Question

A 43-year-old man comes to the office due to fatigue and worsening pedal edema over the past several weeks.  The patient was diagnosed with advanced HIV infection and started on antiretroviral therapy 3 months ago.  He also has a history of hypertension.  Physical examination shows bilateral lower extremity pitting edema.  Serum creatinine is elevated and serum phosphorus is decreased compared to test results 3 months ago.  Urinalysis reveals moderate proteinuria and glucosuria.  Renal biopsy shows cytoplasmic vacuolization in the proximal tubules accompanied by loss of brush border and basement membrane denudation.  Intracytoplasmic eosinophilic inclusions are also seen in the proximal tubules.  There are no significant interstitial inflammatory infiltrates, and the glomeruli appear normal.  Which of the following is the most likely diagnosis in this patient?

Quizplus · Accepted Answer

This patient with HIV was recently started on antiretroviral therapy and subsequently developed evidence of proximal tubule dysfunction (eg, hypophosphatemia, glucosuria, proteinuria, biopsy abnormalities), raising concern for tenofovir-induced nephrotoxicity. Tenofovir is a common part of first-line HIV therapy. It is an adenosine analogue that is a member of the nucleotide reverse transcriptase inhibitors (NRTIs). NRTIs prevent reverse transcriptase from converting the HIV RNA genome into complementary double-stranded DNA, which inhibits viral replication. Tenofovir is primarily eliminated via the proximal tubule cells of the kidney. High concentrations of tenofovir in these cells can interfere with mitochondrial DNA synthesis and result in cellular damage. This typically manifests with acute kidney injury (eg, elevated creatinine, water retention) and/or signs of proximal tubule dysfunction (eg, phosphaturia, glucosuria, proteinuria). Histopathology may show damage to proximal tubule cells (eg, loss of brush border, basement membrane denudation) and evidence of giant mitochondria (eg, large eosinophilic inclusions). Renal abnormalities typically improve once tenofovir is discontinued. (Choice A) HIV-associated nephropathy is due to viral infection of kidney epithelial cells and typically manifests with hematuria, hypertension, and edema. Biopsy classically shows focal segmental glomerulosclerosis and significant interstitial inflammation. (Choice B) Hypertensive nephrosclerosis is most common in black patients who have markedly elevated blood pressure. It usually is characterized by proteinuria with or without renal insufficiency. Biopsy typically reveals damage to the renal vasculature (eg, intimal thickening, luminal narrowing), glomeruli (eg, glomerulosclerosis), and renal interstitium (eg, fibrosis, atrophy). (Choice C) Poststreptococcal glomerulonephritis is an immune complex disease of the glomeruli caused by a preceding infection with a nephritogenic strain of group A beta-hemolytic streptococcus. Patients may have proteinuria, edema, hypertension, and/or acute kidney injury. However, they usually also have red/brown urine and biopsy evidence of diffuse proliferative glomerulonephritis. (Choice E) Trimethoprim-sulfamethoxazole is often used in patients with advanced AIDS to prevent Pneumocystis pneumonia and/or Toxoplasma gondii. It can cause interstitial nephritis and acute kidney injury but does not usually cause focal damage to the proximal tubule. Educational objective: Tenofovir is a nucleotide reverse transcriptase inhibitor that is a common component of HIV therapy. This drug is generally well tolerated but may occasionally cause damage to the proximal tubule of the kidney, leading to acute kidney injury and/or proximal tubule impairment (eg, phosphoruria, glucosuria, proteinuria, water retention). Biopsy typically reveals a normal glomerulus and renal interstitium but damage to the proximal tubule.

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