Which of the following mechanisms is responsible for AKI in rhabdomyolysis?

Explanation

## Pathophysiology of Rhabdomyolysis-Induced AKI **Key Point:** Rhabdomyolysis causes AKI through a multifactorial mechanism dominated by myoglobin-induced tubular injury, cast formation, and oxidative stress—not purely prerenal or immune mechanisms. ### Mechanism of Injury 1. **Myoglobin Release & Filtration** - Muscle breakdown releases myoglobin (MW ~17 kDa), which is freely filtered at the glomerulus. - Myoglobin precipitates in the tubular lumen, especially in acidic urine. 2. **Direct Tubular Toxicity** - Myoglobin and light chains (from myoglobin degradation) are directly nephrotoxic to proximal tubular epithelium. - Generates reactive oxygen species (ROS) and causes lipid peroxidation. - Results in acute tubular necrosis (ATN). 3. **Intratubular Cast Formation & Obstruction** - Myoglobin + Tamm-Horsfall protein (THP) → myoglobin casts. - Casts obstruct the tubular lumen, raising intratubular pressure and reducing GFR. - Acidic urine favors precipitation; alkaline urine reduces cast formation. 4. **Vasoconstriction & Hypoxia** - Myoglobin-induced renal vasoconstriction reduces renal blood flow. - Contributes to ischemic ATN. **High-Yield:** The classic triad of rhabdomyolysis-induced AKI is: - Myoglobin-mediated tubular toxicity - Intratubular obstruction by casts - Renal vasoconstriction **Clinical Pearl:** Aggressive hydration (target urine output 200–300 mL/hr) and urine alkalinization (sodium bicarbonate to maintain urine pH >6.5) are cornerstone therapies because they reduce myoglobin precipitation and cast formation. **Mnemonic:** **RhabdoMYO** → **MYOglobin toxicity + casts + vasoconstriction** = ATN.