In an elderly patient with non‑Hodgkin lymphoma, severe hypertension, diabetes mellitus, chronic use of a potassium‑sparing diuretic, and scheduled for chemotherapy who presented with sudden cardiac arrest and has hyperkalaemia, elevated uric acid, and elevated creatinine, what is the most likely cause of the hyperkalaemia?

Spontaneous Tumor Lysis Syndrome (TLS) is the most likely cause of hyperkalemia in this patient

This patient experienced spontaneous tumor lysis syndrome occurring before chemotherapy initiation, evidenced by the classic triad of hyperkalemia (7.0), hyperuricemia, and acute kidney injury in the setting of high-burden non-Hodgkin lymphoma. 1

Clinical Reasoning

Why TLS is the Primary Diagnosis

The constellation of findings definitively points to TLS rather than the other options:

• Hyperkalemia (K+ 7.0) + Elevated uric acid + Elevated creatinine represents the classic laboratory triad of TLS 1
• Non-Hodgkin lymphoma with high tumor burden places this patient at extreme risk for spontaneous TLS, particularly in elderly patients 2
• Spontaneous TLS occurs BEFORE chemotherapy in 5-10% of high-risk lymphoma cases, contrary to common misconception that TLS only occurs post-chemotherapy 1
• The guidelines explicitly state that TLS "symptoms may occur before the start of chemotherapy" and can develop in "patients who present with TLS or who develop it before therapy initiation" 1

Mechanism of Death

The hyperkalemia from rapid tumor cell lysis directly caused fatal cardiac arrest through:

• Cardiac membrane instability leading to ventricular arrhythmias
• The guidelines specifically identify "cardiac arrest" as a direct consequence of TLS-induced hyperkalemia 1
• Historical case reports document cardiac arrest from hyperkalemia in lymphoproliferative disorders 3

Why NOT the Other Options

Drug-induced hyperkalemia (potassium-sparing diuretics):

• While the patient was on potassium-sparing diuretics, this alone would not explain the simultaneous hyperuricemia and acute kidney injury
• Drug-induced hyperkalemia typically produces gradual elevation, not acute presentation with K+ 7.0 leading to sudden death
• The potassium-sparing diuretic likely exacerbated the TLS-induced hyperkalemia but was not the primary cause 4

Undiscovered chronic renal failure:

• Chronic kidney disease causes gradual hyperkalemia, not acute presentation with sudden cardiac arrest
• Would not explain the elevated uric acid in this acute context
• The elevated creatinine here represents acute kidney injury from uric acid crystal deposition in renal tubules, a hallmark of TLS 1

Renal tubular acidosis (RTA):

• RTA causes hyperkalemia through impaired distal potassium secretion
• Does NOT cause hyperuricemia
• Does NOT cause the acute, life-threatening presentation seen here
• Wrong clinical context entirely

Critical Pathophysiology

In TLS, the mechanism proceeds as follows 1:

1. Spontaneous tumor cell lysis releases massive intracellular contents (potassium, purines, phosphate)
2. Purine catabolism → hyperuricemia → uric acid crystal precipitation in renal tubules
3. Acute kidney injury from crystal nephropathy impairs potassium excretion
4. Hyperkalemia is both directly released from cells AND worsened by renal failure
5. Cardiac arrest from potassium-induced arrhythmias

The potassium-sparing diuretic created a "perfect storm" by further impairing renal potassium excretion in a patient already experiencing TLS 4.

Clinical Pitfalls to Avoid

• Do not assume TLS only occurs after chemotherapy - spontaneous TLS is well-documented in high-burden lymphomas 1
• Recognize the triad: hyperkalemia + hyperuricemia + elevated creatinine = TLS until proven otherwise in lymphoma patients
• Potassium-sparing diuretics should be discontinued in all patients with lymphoproliferative disorders before chemotherapy 4
• High-risk NHL patients require TLS prophylaxis (hydration, allopurinol/rasburicase) even BEFORE chemotherapy initiation 2

Risk Stratification Context

This patient had multiple TLS risk factors 2:

• Non-Hodgkin lymphoma (high-risk malignancy)
• Elderly age (impaired renal reserve)
• Diabetes mellitus (baseline renal dysfunction risk)
• Potassium-sparing diuretic (impaired potassium excretion)
• Likely elevated LDH and tumor burden (scheduled for chemotherapy)

The answer is spontaneous tumor lysis syndrome, with the potassium-sparing diuretic serving as a contributing factor that worsened the hyperkalemia but was not the primary etiology.