Onco-nephrology · KIMS Secunderabad
Tumor Lysis Syndrome — Preventing a Dangerous Complication of Cancer Treatment
Tumor lysis syndrome (TLS) is a life-threatening metabolic emergency that occurs when a large number of cancer cells are rapidly destroyed — either by chemotherapy, radiation, immunotherapy, or sometimes spontaneously in highly proliferative tumours. As tumour cells lyse, they release their intracellular contents into the bloodstream simultaneously: potassium, phosphate, nucleic acids (metabolised to uric acid), and lactate dehydrogenase. The sudden surge of these substances overwhelms the kidneys' capacity to excrete them, causing a characteristic metabolic storm: hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia (from phosphate-calcium binding) — all of which can cause AKI, cardiac arrhythmias, and death.
TLS is most common in haematological malignancies — particularly Burkitt lymphoma (the highest-risk tumour — with an extraordinarily high proliferative rate), acute lymphoblastic leukaemia (ALL), diffuse large B-cell lymphoma (DLBCL), and chronic lymphocytic leukaemia (CLL) treated with targeted agents. Solid tumours rarely cause TLS except in rare cases of highly bulky, rapidly proliferating disease. At KIMS, TLS prevention is a joint responsibility of the oncology team (selecting prophylaxis strategy) and the nephrology team (monitoring kidney function and managing electrolyte emergencies).
The Cairo-Bishop criteria — diagnosis
Laboratory TLS
Two or more of the following within 3 days before or 7 days after the start of chemotherapy: uric acid above 476 µmol/L (8 mg/dL) or 25% increase from baseline · potassium above 6 mEq/L or 25% increase · phosphate above 1.45 mmol/L (4.5 mg/dL) or 25% increase · calcium below 1.75 mmol/L (7 mg/dL) or 25% decrease.
Clinical TLS
Laboratory TLS plus one or more of: AKI (creatinine above 1.5 times the upper limit of normal for age), cardiac arrhythmia, seizure, or death.
Risk stratification — who needs aggressive prophylaxis
High risk
Tumours: Burkitt lymphoma · ALL (high WBC) · DLBCL (bulky, LDH above 2× ULN) · CLL treated with venetoclax. Prophylaxis: IV hydration at 2–3 litres/m²/day starting 24–48 hours before chemotherapy · Rasburicase (urate oxidase — converts uric acid to allantoin, which is far more soluble and rapidly excreted) · Frequent electrolyte monitoring (every 4–6 hours) · ICU-level care during first chemotherapy cycle.
Intermediate risk
Tumours: DLBCL (moderate bulk) · Multiple myeloma (bulky) · High WBC CLL. Prophylaxis: IV hydration · Allopurinol (XO inhibitor — prevents new uric acid synthesis but does not break down existing uric acid) · Electrolyte monitoring every 8–12 hours.
Low risk
Tumours: Most solid tumours · Low-bulk haematological malignancies. Prophylaxis: Oral hydration · Allopurinol · Standard electrolyte monitoring.
Treatment when TLS occurs
IV hydration
Aggressive IV fluid hydration (2 to 3 litres/m²/day) maintains high urine flow, diluting uric acid and phosphate in the tubules. Normal saline is used — alkalinisation with bicarbonate is no longer routinely recommended (it may promote calcium phosphate precipitation in the tubules at alkaline pH).
Rasburicase
The most rapidly effective agent for hyperuricaemia — converts existing uric acid to allantoin, which is far more soluble and rapidly excreted. Results in rapid fall in uric acid within 4 to 24 hours. Preferred over allopurinol for high-risk TLS and for established TLS with hyperuricaemia. Contraindicated in G6PD deficiency — rasburicase generates hydrogen peroxide as a by-product, which causes haemolysis in G6PD-deficient patients. G6PD testing should be performed (or assumed positive in relevant ethnic groups) before rasburicase.
Hyperkalaemia management
Calcium gluconate for cardiac membrane stabilisation if ECG shows peaked T waves or widened QRS. Insulin-dextrose and sodium bicarbonate to shift potassium intracellularly. Sodium polystyrene sulphonate or patiromer for gut potassium binding. Dialysis for refractory hyperkalaemia above 6.5 mEq/L with ECG changes or above 7.0 mEq/L.
Hyperphosphataemia
Oral phosphate binders (calcium carbonate, sevelamer). Dialysis if phosphate rises above 3.0 mmol/L with symptomatic hypocalcaemia.
CRRT for severe TLS-AKI
When TLS causes oliguric AKI, fluid overload, refractory hyperkalaemia, or severe hyperuricaemia/hyperphosphataemia that cannot be managed medically, CRRT provides continuous metabolic control. CRRT is preferred over intermittent HD in haemodynamically unstable patients. At KIMS, CRRT is available 24/7 in the oncology ICU for TLS management in collaboration with the oncology team.
Book a Nephrology-Oncology Consultation at KIMS for TLS Prevention
Frequently Asked Questions — Tumor Lysis Syndrome
TLS is most common in rapidly proliferating haematological malignancies — Burkitt lymphoma (the highest-risk tumour, with a cell doubling time of 24 to 48 hours), acute lymphoblastic leukaemia with high white cell counts, diffuse large B-cell lymphoma with bulky disease, and CLL treated with venetoclax or obinutuzumab (both cause rapid B-cell lysis). Among solid tumours, TLS is rare but has been reported in bulky germ cell tumours, small cell lung cancer, and hepatocellular carcinoma. Any patient with a large tumour burden undergoing systemic cancer therapy should be assessed for TLS risk before treatment begins.
Yes — spontaneous TLS can occur in highly proliferating tumours even before any treatment is given, from rapid spontaneous tumour cell death. Burkitt lymphoma and ALL with very high white cell counts are the most reported tumour types for spontaneous TLS. This is why patients with high-risk haematological malignancies admitted for treatment initiation are placed on IV hydration and allopurinol (or rasburicase if high-risk) as soon as the diagnosis is established — before the first chemotherapy dose.
Allopurinol inhibits xanthine oxidase — the enzyme that converts xanthine to uric acid — preventing new uric acid synthesis. It does not break down existing uric acid. It must be started 24 to 48 hours before chemotherapy to be effective, and it takes 2 to 3 days to lower uric acid. Rasburicase is a recombinant urate oxidase — an enzyme that converts existing uric acid to allantoin (which is 5 to 10 times more soluble). It works on existing uric acid within 4 to 24 hours of administration. Rasburicase is significantly more effective for established hyperuricaemia and high-risk TLS — but it is more expensive and contraindicated in G6PD deficiency. At KIMS, rasburicase is used for high-risk TLS and allopurinol for intermediate-risk prophylaxis.
The hyperphosphataemia of TLS drives hypocalcaemia through two mechanisms: the excess phosphate binds to free calcium in the blood (forming calcium phosphate complexes that are not biologically active), directly reducing serum calcium; and the calcium phosphate complexes deposit in soft tissues and vessels, removing calcium from circulation. Hypocalcaemia causes neuromuscular irritability (tetany — involuntary muscle spasms, particularly of the hands and feet), perioral tingling, and — in severe cases — laryngospasm and cardiac arrhythmias. Symptomatic hypocalcaemia is treated with IV calcium gluconate. Asymptomatic hypocalcaemia without ECG changes is generally not treated with calcium in TLS — because adding calcium to a hyperphosphataemic state promotes calcium phosphate precipitation in tissues.
KIMS Secunderabad — Dr. E. Ravi (Senior Consultant Nephrologist, critical care nephrology), joint nephrology-oncology TLS risk stratification before chemotherapy, rasburicase and allopurinol protocol, CRRT 24/7 in ICU for severe TLS-AKI, G6PD testing before rasburicase, electrolyte monitoring every 4 to 6 hours for high-risk patients. NABH and NABL accredited. Emergency line: 040-4488-5000.