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 (PO43-), and uric acid, that can damage the kidneys and cause renal failure.


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).


Pathophysiology

Tumor cell lysis → release of intracellular components (e.g., K+, PO43-, 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 PO43- binding → hypocalcemia → neuronal excitability → risk of seizures
  • Hyperphosphatemia: PO43- 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.


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

Diagnostics

Hydration is the mainstay of TLS prophylaxis and treatment.


Treatment

  • Hydration is the mainstay of TLS prophylaxis and treatment.
  • Hyperuricemia
    • Allopurinol
      • Indicated as prophylaxis in patients at low to intermediate risk
    • Rasburicase: recombinant uricase that catalyzes the breakdown of uric acid to allantoin
      • Indications
        • Treatment of established TLS
        • Prophylaxis for intermediate to high-risk patients