Ischemic injury in the kidney most rapidly affects which structures?

• A. Proximal tubule and thick ascending limb
• B. Glomerulus
• C. Distal tubule
• D. Collecting duct

Answer: (A)

Ischemic injury hits the parts of the kidney with the highest energy needs first. The proximal tubule and the thick ascending limb of the loop of Henle are the most metabolically active, with lots of mitochondria and heavy Na+/K+ ATPase activity to drive reabsorption. When oxygen delivery is impaired, ATP runs short, so these tubular cells are the first to fail, leading to cell injury or death, loss of the brush border, and tubular dysfunction. The glomerulus is relatively protected by autoregulation, and the distal tubule and collecting duct are less active at baseline, so they are affected later in ischemia. Thus, the proximal tubule and thick ascending limb are the structures most rapidly injured.