Tumor Lysis Associated Acute Kidney Injury

Tumour lysis syndrome (TLS) is a metabolic emergency from massive cell lysis releasing potassium, phosphate and nucleic acids (purine metabolism to uric acid), with AKI as its major complication.

• Highest risk: Burkitt lymphoma, acute lymphoblastic leukaemia, high-grade lymphomas, acute myeloid leukaemia with high white count, bulky chemosensitive tumours; also with venetoclax, rituximab, bortezomib, and spontaneous TLS before therapy.
• Onset 12 to 72 hours after chemotherapy.
• Cairo-Bishop definition (laboratory TLS): two or more of uric acid ≥ 8 mg/dL (476 µmol/L) or 25% rise, potassium ≥ 6 mmol/L, phosphate ≥ 4.5 mg/dL (adults), calcium ≤ 7 mg/dL (1.75 mmol/L), within 3 days before to 7 days after chemotherapy. Clinical TLS adds creatinine ≥ 1.5 times upper limit, arrhythmia, or seizure.
• AKI mechanisms: uric acid and calcium phosphate crystal precipitation in tubules, renal vasoconstriction, volume depletion.
• Mortality is high with AKI requiring dialysis.

• Nausea, vomiting, lethargy, oedema, oliguria, muscle cramps, tetany, paraesthesia.
• Cardiac arrhythmias, sudden death (hyperkalaemia), seizures (hypocalcaemia).
• Flank pain, haematuria (crystal nephropathy).
• Preceding tumour burden: bulky disease, high LDH, high white count (over 50 x 10^9/L).

• Serial measurements every 4 to 6 hours in high-risk patients for the first 48 to 72 hours: potassium, phosphate, calcium, uric acid, creatinine, LDH, bicarbonate.
• ECG for peaked T waves, widened QRS.
• Urinalysis (uric acid crystals), urine output monitoring, renal ultrasound to exclude obstruction.
• Risk stratification: tumour type, burden, renal function at baseline, dehydration.
• Exclude other causes of AKI (sepsis, nephrotoxins, obstruction).

Prevention

• Aggressive hydration with isotonic saline 2 to 3 L/m2/day (3 L/m2/day in high-risk; urine output 80 to 100 mL/m2/h, over 2 mL/kg/h in children).
• Rasburicase 0.2 mg/kg IV over 30 minutes daily for 1 to 7 days (single dose 3 to 6 mg often sufficient; a single 0.2 mg/kg dose is standard in high-risk) for high-risk patients or established hyperuricaemia; contraindicated in G6PD deficiency (check before; risk of haemolysis, methaemoglobinaemia); uric acid samples must be placed on ice.
• Allopurinol 300 to 600 mg daily (100 mg/m2 every 8 hours in children; reduce in renal impairment) starting 1 to 3 days before chemotherapy for low to intermediate risk patients.
• Avoid urinary alkalinisation (increases calcium phosphate precipitation).
• Febuxostat 40 to 120 mg daily is an alternative for allopurinol intolerance.

Established TLS

• Hyperkalaemia: calcium gluconate 10% 10 to 20 mL IV for ECG changes, insulin 10 units with 25 g glucose, salbutamol, polystyrene/potassium binders, early dialysis.
• Hyperphosphataemia: hydration, phosphate binders (sevelamer 800 to 1600 mg with meals, aluminium hydroxide short term).
• Hypocalcaemia: treat only if symptomatic (calcium gluconate 10% 10 to 20 mL slowly), as calcium administration risks precipitation.
• Renal replacement therapy for oliguria with volume overload, refractory hyperkalaemia (over 6.5), phosphate over 10 mg/dL with symptomatic hypocalcaemia, uraemia, acidosis; intermittent haemodialysis or continuous therapy at high dose; early initiation.
• ICU monitoring with telemetry; withhold or delay chemotherapy briefly for spontaneous TLS; in venetoclax therapy use dose ramp-up.
• Follow metabolic panel every 4 to 6 hours until resolved for 24 to 48 hours.