What is the most likely cause of acute renal failure in a 25‑year‑old woman with acute lymphoblastic leukemia receiving chemotherapy who presents with periorbital edema, obstructive uropathy, normal sodium, hyperkalemia, hypocalcemia, hyperphosphatemia, and markedly elevated creatinine?

Uric Acid Nephropathy (Tumor Lysis Syndrome)

The cause of acute renal failure in this patient is uric acid nephropathy secondary to tumor lysis syndrome (TLS).

Clinical Reasoning

This 25-year-old woman with acute lymphoblastic leukemia (ALL) on chemotherapy presents with the classic constellation of TLS: hyperkalemia, hypocalcemia, hyperphosphatemia, and markedly elevated creatinine (300 μmol/L or ~3.4 mg/dL) with obstructive uropathy 1. The periorbital edema reflects fluid overload from acute kidney injury.

Why Uric Acid Nephropathy?

ALL is a high-risk malignancy for TLS due to its high proliferative rate, large tumor burden, and extreme sensitivity to chemotherapy 1. When chemotherapy induces rapid tumor cell lysis, massive quantities of intracellular contents—including nucleic acids—are released into the bloodstream. Purine nucleic acids are catabolized to uric acid, which precipitates as crystals in the renal tubules when concentrations exceed solubility limits (approximately 15 mg/dL at urine pH ~5), causing obstructive uropathy and acute renal failure 1.

The Electrolyte Pattern is Diagnostic

The specific laboratory abnormalities confirm TLS 1:

• Hyperkalemia: Released from lysed tumor cells
• Hyperphosphatemia: Massive release of intracellular phosphate
• Hypocalcemia: Results from calcium-phosphate precipitation
• Normal sodium: Excludes primary volume depletion
• Elevated creatinine: Acute kidney injury from crystal deposition

This triad of hyperkalemia, hyperphosphatemia, and hypocalcemia occurring simultaneously in a patient with hematologic malignancy receiving chemotherapy is pathognomonic for TLS 1.

Why Not the Other Options?

• Hypercalcemia is EXCLUDED: The patient has hypocalcemia, not hypercalcemia. Hypercalcemia would not cause this electrolyte pattern.

• Septicemia is unlikely: While sepsis can cause acute kidney injury, it would not produce this specific constellation of hyperkalemia, hyperphosphatemia, and hypocalcemia. The obstructive uropathy from crystal deposition is characteristic of TLS, not sepsis 1.

• Hypertensive nephropathy is implausible: There is no mention of hypertension, and hypertensive nephropathy develops over years, not acutely during chemotherapy. It would not cause this acute electrolyte derangement pattern.

Critical Management Points

Immediate treatment is required to prevent life-threatening complications 2:

1. Aggressive IV hydration (maintain urine output ≥100 mL/hour) through central venous access
2. Rasburicase (recombinant urate oxidase) to rapidly degrade uric acid—superior to allopurinol in established TLS 2
3. Avoid potassium, calcium, and phosphate in IV fluids initially
4. Manage hyperkalemia aggressively: insulin/glucose, calcium gluconate for cardiac protection, sodium polystyrene 2
5. Consider urgent hemodialysis if severe hyperkalemia (>6 mmol/L), rapidly rising phosphate, or oliguria develops 2

Common Pitfall to Avoid

Do NOT alkalinize the urine in this setting. While historically recommended, urinary alkalinization can paradoxically worsen calcium-phosphate precipitation in the renal tubules, exacerbating kidney injury 2, 3. Loop diuretics or mannitol should be used to maintain urine output, but avoid alkalinization when hyperphosphatemia is present 2.

The obstructive uropathy noted by the urologist represents intratubular crystal deposition (uric acid and/or calcium-phosphate), which is the hallmark pathophysiologic mechanism of TLS-induced acute kidney injury 1, 2.