A 65-year-old woman is treated with gentamicin for an abdominal infection complicated by multidrug-resistant organisms. After a week of treatment, the patient's urine output decreases noticeably, and serum creatinine rises to 2.3 mg/dL. She has no previous kidney disease, and baseline kidney function was normal prior to the initiation of therapy. The patient has remained afebrile for 24 hours. Blood pressure is 130/80 mm Hg and pulse is 80/min. Examination shows moist mucous membranes. There is no rash. Results of urinalysis are as follows: Fractional excretion of sodium is 2%. Histologic examination of the patient's kidneys would most likely show which of the following?

Question

A 65-year-old woman is treated with gentamicin for an abdominal infection complicated by multidrug-resistant organisms.  After a week of treatment, the patient's urine output decreases noticeably, and serum creatinine rises to 2.3 mg/dL.  She has no previous kidney disease, and baseline kidney function was normal prior to the initiation of therapy.  The patient has remained afebrile for 24 hours.  Blood pressure is 130/80 mm Hg and pulse is 80/min.  Examination shows moist mucous membranes.  There is no rash.  Results of urinalysis are as follows:  Fractional excretion of sodium is >2%.  Histologic examination of the patient's kidneys would most likely show which of the following?

Quizplus · Accepted Answer

11ec160b_3a27_c9ca_9249_8f40a768baeb_MD0001_00 Aminoglycosides (eg, gentamicin, tobramycin) are bactericidal antibiotics that bind to the 30S ribosomal subunit and inhibit protein synthesis. They are commonly used for severe gram-negative infections but carry a significant risk of acute kidney injury. Aminoglycosides are filtered across the glomerulus and concentrate within the proximal renal tubules, where they impair lysosomal function, protein synthesis, and mitochondrial activity, leading to acute tubular necrosis (ATN). This is visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane. Aminoglycoside-induced kidney injury typically manifests within 1 week of therapy initiation. Due to the high intratubular drug concentrations, ATN can occur despite normal serum drug levels. Proximal tubular dysfunction results in loss of resorptive capacity and electrolyte wasting (eg, hypomagnesemia, hypophosphatemia); severe disease can result in Fanconi syndrome (ie, aminoaciduria, glucosuria, uricosuria, phosphaturia). Distal tubular injury may also occur and results in loss of concentrating capacity with polyuria (nonoliguric renal failure). Urinalysis typically demonstrates mild proteinuria with granular or hyaline casts. Consistent with other causes of ATN, the fractional excretion of sodium (FENa) is >2%. (Choices B and E) Leukocytic infiltration of the glomerular capillaries is seen with vasculitides (eg, granulomatosis with polyangiitis) that cause glomerulonephritis. Chronic glomerulonephritis is characterized by protracted inflammation with collagenous replacement of the glomeruli. However, nephritic diseases typically cause hypertension, hematuria, and red blood cell casts on urinalysis. (Choice C) Leukocytic infiltration of the interstitium and tubules is seen in acute interstitial nephritis, a common cause of kidney injury that often occurs after introduction of a new drug. However, patients typically have fever and rash, and urinalysis shows pyuria and white blood cell casts. (Choice D) Patients with prerenal causes of kidney injury (eg, dehydration, blood loss) have normal renal architecture. However, the FENa in prerenal disease is <1%, and the patient would be expected to have signs of hypovolemia (eg, dry mucous membranes). Educational objective: Aminoglycosides are filtered across the glomerulus and concentrate in the renal tubules, leading to proximal tubular injury and acute tubular necrosis. This is visualized histologically as focal tubular epithelial necrosis, often with extensive granular casts that obstruct the tubular lumen and lead to rupture of the basement membrane.

A 65-Year-Old Woman Is Treated with Gentamicin for an Abdominal