A 42-year-old man is admitted with acute kidney injury following a motor vehicle accident with crush injury to both legs. Laboratory findings show serum creatinine 4.2 mg/dL, potassium 6.8 mEq/L, phosphate 7.5 mg/dL, and uric acid 12.4 mg/dL. Urine dipstick is positive for blood but microscopy shows no RBCs. What is the most common mechanism of acute kidney injury in rhabdomyolysis?

Explanation

## Mechanism of Rhabdomyolysis-Induced Acute Kidney Injury **Key Point:** Myoglobin precipitation and tubular obstruction is the primary mechanism of AKI in rhabdomyolysis. The combination of myoglobinuria (positive dipstick for blood without RBCs on microscopy) and acidic urine creates conditions for myoglobin precipitation in the proximal tubule. ### Pathophysiology of Rhabdomyolysis-Induced AKI ```mermaid flowchart TD A[Muscle injury/necrosis]:::outcome --> B[Release of myoglobin & potassium]:::outcome B --> C{Urine pH & volume?}:::decision C -->|Acidic + Low volume| D[Myoglobin precipitation in tubule]:::action D --> E[Tubular obstruction & back-leak]:::outcome E --> F[Acute tubular necrosis]:::outcome C -->|Alkaline + High volume| G[Myoglobin remains soluble]:::action G --> H[Reduced AKI risk]:::outcome B --> I[Hyperkalemia, hyperphosphatemia, hyperuricemia]:::outcome I --> J[Secondary complications]:::action ``` ### Key Diagnostic Clue **High-Yield:** The **positive urine dipstick for blood WITHOUT RBCs on microscopy** is pathognomonic for myoglobinuria. This occurs because: - Myoglobin is a smaller heme-containing protein that reacts with the peroxidase-like activity on the dipstick. - RBCs are absent on microscopy because the blood detected is from myoglobin, not intact erythrocytes. ### Mechanisms of Myoglobin-Induced Injury | Mechanism | Contribution | Preventability | |-----------|--------------|----------------| | **Tubular obstruction** | 40–50% (PRIMARY) | High — alkalinize urine | | Direct tubular toxicity | 20–30% | Moderate — hydration | | Oxidative stress & iron release | 10–20% | Moderate — antioxidants | | Hyperkalemia complications | 5–10% | High — K^+^ management | **Clinical Pearl:** The presence of myoglobinuria without RBCs, combined with elevated creatine kinase (CK) >5000 IU/L and hyperkalemia, confirms rhabdomyolysis-induced AKI. The key therapeutic intervention is aggressive IV hydration to maintain urine output >200 mL/hr and alkalinize urine (target pH >6.5) to prevent myoglobin precipitation. ### Why Myoglobin Precipitates in Acidic Urine Myoglobin solubility is pH-dependent: - **Alkaline urine (pH >6.5)**: Myoglobin remains soluble → minimal precipitation → lower AKI risk. - **Acidic urine (pH <5.5)**: Myoglobin precipitates → tubular obstruction → severe AKI. This is why **sodium bicarbonate infusion** (to alkalinize urine) is a cornerstone of rhabdomyolysis management. **Mnemonic for Rhabdo Complications: **CRASH** - **C**reatine kinase elevation (>5000 IU/L) - **R**habdomyolysis-induced AKI - **A**cute tubular necrosis (myoglobin-mediated) - **S**evere hyperkalemia (cardiac dysrhythmia risk) - **H**yperphosphatemia & hypocalcemia (secondary) [cite:Harrison 21e Ch 279]