Study day december 13

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Tumor Lysis Syndrome – Teaching Points

Core Concept

  • Tumor lysis syndrome (TLS) occurs due to rapid destruction of tumor cells with release of intracellular contents.

  • TLS is most likely in tumors with high cell burden or rapid turnover, such as diffuse large B-cell lymphoma.

  • TLS typically develops within days after starting chemotherapy or immunotherapy.

Characteristic Laboratory Abnormalities

  • TLS classically causes:

    • Hyperphosphatemia

    • Hyperkalemia

    • Hyperuricemia

    • Hypocalcemia

  • Hypocalcemia occurs because phosphate binds calcium to form calcium-phosphate complexes.

Acute Kidney Injury in TLS

  • The most common cause of AKI in TLS is acute nephrocalcinosis.

  • Acute nephrocalcinosis results from calcium phosphate deposition in the renal tubules and interstitium.

  • Phosphate nephropathy leads to AKI via tubular obstruction and direct tubular injury.

  • Uric acid nephropathy usually requires uric acid levels >15 mg/dL and is now less common due to effective prophylaxis.

Why AKI Occurs Despite Rasburicase

  • Rasburicase lowers uric acid by converting uric acid to allantoin.

  • Despite urate-lowering therapy, AKI still occurs because phosphate nephropathy remains common.

  • In modern TLS, AKI is more often due to calcium phosphate precipitation rather than uric acid stone formation.

TLS Prophylaxis

  • TLS prophylaxis includes aggressive intravenous fluids and urate-lowering therapy.

  • Xanthine oxidase inhibitors used for prophylaxis include allopurinol and febuxostat.

  • Rasburicase is preferred in patients with high-risk TLS or underlying kidney disease.

TLS Management

  • Management of severe TLS includes:

    • Intravenous fluids

    • Continuous cardiac telemetry

    • Frequent electrolyte monitoring and correction

  • Hemodialysis is indicated in severe cases, such as when the calcium–phosphate product is ≥70 mg²/dL².

Differential Diagnosis – Why Other Causes Are Less Likely

  • Cyclophosphamide toxicity typically causes hemorrhagic cystitis, not electrolyte-driven AKI.

  • Renal infiltration by lymphoma usually causes insidious kidney injury, not abrupt electrolyte abnormalities.

  • Rituximab hypersensitivity presents with fever, chills, hypotension, or urticaria, which are absent here.

  • Xanthinuria-related AKI occurs with xanthine oxidase inhibitor therapy, not rasburicase.

High-Yield Clinical Pearl

  • In modern tumor lysis syndrome, the most common cause of acute kidney injury is phosphate-mediated acute nephrocalcinosis, not uric acid nephropathy.

Administer the single-item screening test or Alcohol Use Disorders Identification Test–C (AUDIT-C)

Why this is correct

  • This patient is asymptomatic and presenting for a routine primary care visit.

  • Current guidelines (eg, USPSTF) recommend universal screening for unhealthy alcohol use in adults using brief, validated screening tools.

  • The preferred initial screening tests in primary care are:

    • Single-item alcohol screening question, or

    • AUDIT-C (3-question abbreviated AUDIT)

These tools are:

  • Quick

  • Highly sensitive

  • Designed for initial detection, not diagnosis

What the preferred screening tools look like

Single-item screening question

“How many times in the past year have you had 5 or more drinks in a day (for men), or 4 or more drinks in a day (for women)?”

  • ≥1 = positive screen

AUDIT-C

  • Assesses frequency, quantity, and binge drinking

  • Positive screen → proceed to full assessment (eg, full AUDIT, DSM-5 criteria)

High-yield teaching pearl

Unhealthy alcohol use screening in primary care should start with a brief validated tool (single-item screen or AUDIT-C), not CAGE or laboratory tests.

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