Tumor lysis syndrome

Definition

A potentially life-threatening oncologic emergency resulting from the rapid destruction of tumor cells, which leads to a massive release of intracellular components, e.g., potassium (K⁺), phosphate (PO₄^3-), and uric acid, that can damage the kidneys and cause renal failure.

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Etiology

most commonly occurs after initiating cytotoxic treatment in patients with hematologic malignancies (e.g., ALL, AML, or NHL).most commonly occurs after initiating cytotoxic treatment in patients with hematologic malignancies (e.g., ALL, AML, or NHL).

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Pathophysiology

Tumor cell lysis → release of intracellular components (e.g., K⁺, PO₄^3-, nucleic acids) into the bloodstream

• ↑ Nucleic acid → conversion to uric acid → hyperuricemia → urate nephropathy and risk of acute kidney injury
  • Uric acid (pKa = 5.4) is soluble at physiologic pH, but precipitates in an acidic environment. The lowest pH along the nephron is found in the distal tubules and collecting ducts; so these are the segments of the nephron that become obstructed by uric acid crystals. Obstructive uropathy and acute renal failure follow.
• ↓ Ca²⁺ secondary to PO₄^3- binding → hypocalcemia → neuronal excitability → risk of seizures
• Hyperphosphatemia: PO₄^3- binds Ca²⁺ and forms calcium phosphate crystals that obstruct renal tubules → acute kidney injury
• Hyperkalemia: changes in resting membrane potential → risk of cardiac arrhythmias

Mnemonic

Think of “PUKE calcium” to remember the electrolytes affected in tumor lysis syndrome: Phosphorus, Uric acid, and potassium (K⁺) are Elevated; Calcium is decreased.

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Clinical features

• Renal failure: e.g., edema, lethargy, oliguria
• Hyperkalemia: e.g., cardiac arrhythmias, nausea, vomiting, and diarrhea
• Hypocalcemia: e.g., tetany, muscle cramps, seizures

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Diagnostics

Hydration is the mainstay of TLS prophylaxis and treatment.

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Treatment

• Prophylaxis (Pre-chemo):
  • Aggressive IVF: Isotonic fluids (target UOP > 80–100 mL/m²/hr). c
  • Rasburicase: First-line for high risk (degrades urate to allantoin). CI in G6PD deficiency (causes hemolysis/methemoglobinemia).
  • Allopurinol: For low/intermediate risk (prevents new uric acid synthesis only).
• Active TLS Treatment:
  1. IVF + Rasburicase immediately.
  2. Hyperkalemia: Calcium gluconate (only if ECG changes), Insulin + D50, K⁺-binders.
  3. Hypocalcemia: Treat only if symptomatic (prevents metastatic Ca-Phosphate precipitation).
  4. Emergent Hemodialysis: Indications include refractory ↑K⁺, severe ↑Phos, symptomatic ↓Ca²⁺, or uremic AKI/volume overload.