Destruction of skeletal muscle (rhabdomyolysis) releases myoglobin, causing rhabdomyolysis-induced acute renal injury (rhAKI). As rhAKI commonly occurs in austere environments such as earthquakes and armed conflict, supportive care is challenging. Specific therapy would be a significant advance. Since myoglobin is taken into renal tubular cells via the renal cortex-specific transporter megalin (LRP2), we hypothesized that interfering with megalin would ameliorate rhAKI.