What is the cause of hyperkalemia, elevated creatinine indicating impaired renal function, and hyperuricemia in a patient 2 days after starting radiotherapy following mastectomy surgery?

Radiotherapy-Induced Tumor Lysis Syndrome

The most likely cause of this patient's laboratory abnormalities is radiotherapy-induced tumor lysis syndrome (Answer A). The triad of hyperkalemia (6.7 mmol/L), acute kidney injury (creatinine 730), and hyperuricemia occurring 2 days after initiating radiotherapy following mastectomy is pathognomonic for tumor lysis syndrome (TLS). 1

Pathophysiology Supporting This Diagnosis

Radiation therapy can trigger massive tumor cell lysis, leading to the release of intracellular contents into the bloodstream, including potassium, uric acid, and phosphate. 1 The clinical presentation typically manifests within 12-72 hours after initiation of cytoreductive therapy, which matches this patient's timeline perfectly. 1

The mechanism involves:

• Hyperuricemia: Purine nucleic acids from lysed tumor cells are catabolized to uric acid, which precipitates in renal tubules at the acidic pH of distal tubules (pH ~5), where uric acid solubility is only ~15 mg/dL. 1
• Hyperkalemia: Rapid release of intracellular potassium from lysed cells, exacerbated by concurrent renal failure. 1
• Acute kidney injury: Uric acid crystal deposition in renal tubules causes obstruction and renal insufficiency, reflected in the markedly elevated creatinine. 1

Why Other Options Are Less Likely

Option B (inadequate hydration during chemotherapy) is incorrect because the question states the patient just started radiotherapy after mastectomy—there is no mention of chemotherapy administration. 1

Option C (glomerulonephritis) would not explain the constellation of hyperkalemia, hyperuricemia, and the acute temporal relationship with radiotherapy initiation. Glomerulonephritis typically presents with proteinuria, hematuria, and a more gradual decline in renal function. 2

Option D (drug-induced nephrotoxicity) is less likely given the acute presentation immediately following radiotherapy and the specific pattern of metabolic derangements. While nephrotoxic agents can cause renal failure, they don't typically produce the characteristic hyperuricemia and hyperkalemia pattern seen here. 1

TLS in Solid Tumors: An Important Caveat

While TLS is classically associated with hematologic malignancies, it can occur with solid tumors, particularly breast cancer. 3, 2 TLS in solid tumors carries a surprisingly high fatality rate (nearly 35%) compared to hematologic malignancies, likely due to delayed recognition and less vigilant monitoring. 1

Risk factors for TLS in solid tumors include:

• Bulky disease, especially with massive liver metastases 1
• High sensitivity to treatment (chemotherapy or radiotherapy) 1
• Pre-existing renal impairment 1
• Elevated LDH levels (>2× upper normal limit) 1

Immediate Management Required

This patient requires urgent intervention given the life-threatening hyperkalemia (6.7 mmol/L) and severe acute kidney injury:

Hyperkalemia Management

• Immediate cardiac monitoring for arrhythmias, ventricular tachycardia, or cardiac arrest risk 1
• Hypertonic glucose with insulin, calcium gluconate for cardiac membrane stabilization, and potassium-binding resins 4

Renal Replacement Therapy Indications

Dialysis should be initiated immediately for this patient based on:

• Persistent severe hyperkalemia (>6.5 mmol/L) 1, 5
• Severe renal impairment (creatinine 730) 1, 5
• Likely severe metabolic acidosis (not provided but expected) 1, 5

Frequent (daily) dialysis is recommended considering the continuous release of metabolites from ongoing tumor cell lysis. 1

Uric Acid Management

• Rasburicase 0.20 mg/kg/day as a 30-minute infusion is the preferred agent for established TLS with hyperuricemia, as it rapidly converts uric acid to the more soluble allantoin. 1, 6, 7
• Allopurinol alone is insufficient once TLS has developed, though it should be started after rasburicase therapy. 1, 8

Hydration

• Aggressive intravenous hydration (≥2 L/m²/day) to improve renal perfusion and promote urinary excretion of uric acid and phosphate. 1

Critical Pitfall to Avoid

The most dangerous pitfall is failing to recognize TLS in solid tumor patients receiving radiotherapy. Clinicians often associate TLS exclusively with chemotherapy for hematologic malignancies, leading to delayed diagnosis and treatment in breast cancer patients receiving radiation. 1, 3 This delay contributes to the higher mortality rate observed in solid tumor TLS. 1