Tumour lysis syndrome

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Tumour lysis syndrome is an oncological and renal emergency caused when malignant cells release intracellular contents faster than physiological clearance. It may occur spontaneously, after corticosteroid prephase, at the start of chemotherapy, after an antibody or small-molecule treatment, or occasionally after radiotherapy. The highest-risk combination is a rapidly proliferating, highly treatment-sensitive blood cancer with large burden and impaired renal reserve. Solid tumours are usually lower risk but become important when bulky, treatment-sensitive, metastatic to liver or accompanied by kidney impairment.

The characteristic biochemical direction is rising potassium, phosphate and urate with falling calcium and worsening renal function. Cairo-Bishop laboratory TLS classically requires at least two qualifying abnormalities within three days before to seven days after treatment: urate at least 476 micromol/L, potassium at least 6 mmol/L, adult phosphate at least 1.45 mmol/L or corrected calcium at most 1.75 mmol/L, historically also allowing a 25 percent change. Clinical TLS adds acute kidney injury, arrhythmia, sudden death or seizure. These definitions support classification and audit; a dangerous individual abnormality is treated immediately rather than waiting for two criteria or a percentage change.

Prevention is safer than rescue. Before therapy, stratify the cancer and patient, correct dehydration, review nephrotoxins and obstruction, choose an appropriate monitored setting and arrange laboratory capacity. Use isotonic hydration with close weight, urine and respiratory assessment, avoiding fixed high volumes in heart or kidney failure. Allopurinol prevents new urate formation and is suited to many intermediate-risk patients. Rasburicase removes existing urate rapidly and is used for high-risk or established disease, but requires a G6PD safety assessment and special sample handling.

Established TLS needs parallel treatment of the clone and each physiological consequence. Continuous ECG and urgent potassium therapy prevent sudden death. Phosphate control depends on stopping exogenous load, renal clearance and dialysis when severe; asymptomatic low calcium is usually tolerated because calcium administration can increase calcium-phosphate deposition. Give intravenous calcium for seizure, tetany, arrhythmia or other threatening manifestations. Early renal involvement matters because intermittent or continuous renal replacement may be needed before conventional uraemic thresholds when potassium, phosphate, fluid or metabolic rebound cannot be controlled.

Key points

TLS releases potassium, phosphate and nucleic acid from malignant cells; phosphate lowers calcium and purines become uric acid, producing arrhythmia, seizure and acute kidney injury.
Assess risk before treatment from malignancy type, burden, LDH, white-cell count, treatment sensitivity, baseline urate, renal function, hydration, obstruction and nephrotoxic medicines.
First-line baseline tests are potassium, phosphate, adjusted and preferably ionised calcium when symptomatic, urate, creatinine, urea, bicarbonate, LDH, FBC, ECG and accurate fluid balance.
Low-risk disease generally receives monitoring and hydration; intermediate risk adds allopurinol, while high risk needs monitored care, vigorous but safe hydration and rasburicase according to the current BSH pathway.
Allopurinol prevents formation of new uric acid but does not remove existing urate; rasburicase rapidly degrades existing urate and is preferred for high-risk or established TLS.
Rasburicase is contraindicated in G6PD deficiency because it can cause haemolysis and methaemoglobinaemia; after dosing, urate specimens must be kept cold to prevent falsely low ex-vivo results.
Do not alkalinise urine routinely, do not add potassium or phosphate to maintenance fluid and do not give calcium for asymptomatic hypocalcaemia while phosphate is high.
Treat life-threatening potassium immediately and involve renal medicine early for oliguria, fluid overload, refractory hyperkalaemia, severe phosphate burden or persistent metabolic rebound.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Highly treatment-sensitive malignancy

Burkitt lymphoma, lymphoblastic lymphoma, acute leukaemia and other rapidly proliferating blood cancers can release a large intracellular load within hours of effective therapy.

Large active tumour burden

Bulky nodal or visceral disease, high circulating blasts, high LDH and extensive marrow involvement increase the amount of potassium, phosphate and nucleic acid available for release.

Impaired renal clearance

Pre-existing kidney disease, dehydration, oliguria, obstructive uropathy and nephrotoxic medicines reduce the capacity to excrete urate, phosphate and potassium during lysis.

Spontaneous or delayed lysis

TLS may precede treatment or follow corticosteroids, antibodies, targeted agents, radiotherapy or conventional chemotherapy, so risk is linked to biological response rather than one drug class.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Potassium release depolarises myocardium
Intracellular potassium enters plasma faster than renal excretion, disrupting membrane potentials and causing weakness, conduction disturbance, ventricular arrhythmia or cardiac arrest.
2
Phosphate binds circulating calcium
Released phosphate complexes with calcium, lowering ionised calcium and promoting intrarenal and soft-tissue calcium-phosphate deposition, especially when kidney function declines.
3
Purines become uric acid
Nucleic acids are metabolised through xanthine to uric acid, which can crystallise in acidic tubules and compound renal vasoconstriction and inflammation.
4
Kidney injury amplifies lysis
Urate, calcium-phosphate deposition, dehydration and tumour-related obstruction reduce filtration, causing further retention of potassium, phosphate and urate in a self-reinforcing emergency.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

High-risk treatment window

Symptoms or biochemical change can begin before therapy or within hours to days after an effective first dose, including corticosteroid or targeted treatment.

Cardiac potassium toxicityRed flag

Weakness, paraesthesia, bradycardia, broad QRS, loss of P waves, sine-wave change or ventricular arrhythmia is an immediate resuscitation problem.

Hypocalcaemic neuromuscular toxicityRed flag

Perioral tingling, cramp, carpopedal spasm, tetany, seizure, laryngospasm or QT prolongation indicates clinically important ionised calcium reduction.

Renal deteriorationRed flag

Nausea, flank discomfort, oliguria, rising creatinine, hypertension, pulmonary oedema or encephalopathy suggests clearance failure and accumulating metabolic burden.

Silent biochemical TLS

Serial tests may reveal rising urate, phosphate and potassium before symptoms, creating the opportunity for escalation before irreversible organ injury.

Red flags requiring action

ECG change, muscle weakness, bradycardia, ventricular arrhythmia or potassium at a severe threshold needs immediate UK Kidney Association hyperkalaemia treatment while tumour lysis is controlled.
Seizure, tetany, laryngospasm or QT prolongation with low calcium requires monitored calcium treatment, whereas asymptomatic hypocalcaemia during hyperphosphataemia is not routinely corrected.
Falling urine output, rapidly increasing creatinine, fluid overload or biochemical rebound despite rasburicase requires immediate renal review for renal replacement therapy.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line lysis profile and ECGFirst stepFirst line
Why
Detect the biochemical pattern and immediately dangerous membrane toxicity.
Interpretation and limitations
Measure rapidly processed potassium, phosphate, calcium, urate, creatinine, urea, bicarbonate and LDH with ECG; use ionised calcium when symptomatic or critically ill.
02
Confirm risk before cancer treatment
Why
Match prophylaxis, location and monitoring intensity to expected cell death and clearance reserve.
Interpretation and limitations
Combine diagnosis, bulk, LDH, white-cell count, treatment sensitivity and prior response with renal function, urate, hydration, obstruction and interacting medicines.
03
Serial laboratory trend
Why
Identify rapid direction and rebound that a single normal baseline cannot exclude.
Interpretation and limitations
In high risk or established TLS repeat potassium, phosphate, calcium, urate and renal function commonly every 4 to 6 hours, using shorter intervals for instability or hyperkalaemia.
04
Classification against accepted criteria
Why
Standardise communication of laboratory and clinical TLS without delaying treatment.
Interpretation and limitations
Record qualifying abnormalities and organ events within the treatment window, but treat severe potassium, symptoms or oliguria even when formal criteria are incomplete.
05
Cause and clearance assessment
Why
Find sepsis, obstruction, medicine toxicity or artefact that changes immediate support.
Interpretation and limitations
Use cultures, lactate, urine output, fluid examination, imaging for obstruction and repeat non-haemolysed potassium; request CK or haemolysis tests when another cell-breakdown source is plausible.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Sepsis-associated acute kidney injury

Sepsis causes hypotension, lactate rise, oliguria and electrolyte disturbance and may coexist in neutropenia; cultures and antimicrobial treatment proceed without delaying lysis management.

Pseudohyperkalaemia

Haemolysis, thrombocytosis or fragile extreme leukocytosis can raise laboratory potassium; ECG and an urgently processed plasma or blood-gas sample distinguish artefact without dismissing true lysis.

Rhabdomyolysis or haemolysis

Muscle or red-cell destruction also releases potassium and phosphate; creatine kinase, haemolysis markers, urate pattern and treatment chronology help identify the dominant source.

Drug or renal electrolyte disorder

Renin-angiotensin blockade, potassium-sparing diuretics, calcineurin inhibitors, acidosis and established kidney failure can produce dangerous potassium without the full lysis pattern.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Before anticancer therapyStratify and prevent lysisFirst stepA treatment-responsive malignancy is about to receive systemic therapy, corticosteroid prephase or another rapid tumour-reducing intervention.

1Classify tumour and patient risk using diagnosis, burden, LDH, white-cell count, renal reserve, urate, hydration, obstruction and planned treatment.
2Correct volume depletion, stop avoidable nephrotoxins and potassium or phosphate supplements and choose ward, high-dependency or ambulatory monitoring appropriate to risk.
3Use hydration alone for selected low risk, add renal-adjusted allopurinol for intermediate risk and use rasburicase with close monitoring for high risk under the BSH pathway.

02Established biochemical TLSRemove urate and protect clearancePotassium, phosphate or urate rises with falling calcium or renal function around tumour reduction.

1Call haematology or oncology and renal medicine, start ECG monitoring, repeat a rapidly processed lysis panel and assess fluid, urine, neurological and respiratory status.
2Give rasburicase when indicated, use carefully titrated isotonic fluid without potassium or phosphate and continue effective clone-directed treatment unless the treating team pauses it for instability.
3EscalationMeasure lysis chemistry at least every 4 to 6 hours and escalate early to critical care and renal replacement if potassium, phosphate, fluid or uraemia cannot be controlled.

03Dangerous potassiumTreat hyperkalaemia immediatelySevere potassium, ECG change, muscle weakness or arrhythmia develops during suspected or established TLS.

1Follow the UK Kidney Association emergency algorithm: protect the myocardium with intravenous calcium when ECG toxicity is present and place the patient on continuous monitoring.
2Shift potassium intracellularly with intravenous soluble insulin and glucose and use nebulised salbutamol as an adjunct where appropriate, checking glucose repeatedly for delayed hypoglycaemia.
3Remove ongoing potassium through renal excretion or urgent renal replacement and repeat potassium early because shifting therapy is temporary and cell lysis continues.

04Low calcium with high phosphateTreat symptoms, not the numberCalcium falls as phosphate rises during TLS.

1Check ionised calcium, ECG and symptoms and stop calcium-containing maintenance or phosphate exposure that is not clinically required.
2Do not routinely give calcium for asymptomatic hypocalcaemia because it may promote calcium-phosphate precipitation in kidney and tissue.
3For seizure, tetany, laryngospasm or arrhythmia, give monitored intravenous calcium gluconate while urgently lowering phosphate and arranging renal support.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Intermediate-risk prophylaxis that inhibits xanthine oxidase and prevents formation of additional uric acid.

Allopurinol

Give 300 mg orally once daily, or 100 mg three times daily, usually starting 24 to 48 hours before tumour-reducing treatment and continuing until the lysis-risk period has passed; reduce dose for renal impairment under the haematology protocol.

It does not lower existing urate and can increase xanthine load. Stop for serious rash or hypersensitivity, review renal and liver function and reduce azathioprine or mercaptopurine drastically or avoid the combination because xanthine oxidase inhibition raises exposure.

Preferred rapid urate removal for high-risk prophylaxis and established TLS because it converts existing uric acid to soluble allantoin.

Rasburicase

Give 0.2 mg/kg intravenously once daily as a 30-minute infusion for up to 7 days, with duration determined by baseline burden, treatment response and serial urate under the current BSH and product protocol.

Contraindicated in G6PD deficiency because hydrogen peroxide generation can cause severe haemolysis and methaemoglobinaemia. Do not administer concurrently in the same line as chemotherapy; collect post-dose urate into pre-chilled tubes and transport on ice.

Temporarily shifts potassium into cells while tumour lysis is stopped and renal removal or dialysis is arranged.

Soluble insulin with glucose

For severe adult hyperkalaemia, give 10 units soluble insulin intravenously with 25 g glucose under the UK Kidney Association algorithm; add 10% glucose at 50 mL/hour for 5 hours when the pretreatment glucose is below 7 mmol/L.

Hypoglycaemia may be delayed for hours. Check capillary glucose before treatment and serially for at least 6 hours, use lower or individualised regimens only through the current renal protocol and never mistake a temporary potassium fall for removal.

Stabilises threatening tetany, seizure, laryngospasm or electrical instability while phosphate burden is reduced.

Calcium gluconate 10%

For symptomatic hypocalcaemia, give 10 to 20 mL of 10% calcium gluconate diluted in 50 to 100 mL of 5% glucose intravenously over 10 minutes with continuous ECG monitoring, repeating according to symptoms and ionised calcium.

Do not correct asymptomatic hypocalcaemia routinely during hyperphosphataemia. Avoid extravasation, use specialist caution with digoxin and recognise that calcium administration can increase calcium-phosphate precipitation when phosphate remains high.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Malignant arrhythmia

Rapid potassium rise and interacting calcium disturbance can cause conduction block, ventricular fibrillation, pulseless electrical activity and sudden death before other symptoms develop.

Seizure and neuromuscular irritability

Falling ionised calcium causes paraesthesia, cramps, tetany, laryngospasm, seizure and prolonged repolarisation, particularly when phosphate remains markedly elevated.

Acute kidney injury

Crystal and calcium-phosphate deposition, hypovolaemia and tumour obstruction can produce oliguria, uraemia, fluid overload and a requirement for dialysis.

Interrupted cancer treatment

Critical illness, renal failure and metabolic instability can delay curative therapy, alter drug clearance and increase early mortality from both malignancy and treatment toxicity.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Before treatment, document FBC, LDH, potassium, phosphate, calcium, urate, creatinine, bicarbonate, weight, urine output, fluid status, ECG when indicated and the assigned TLS-risk category.
In high-risk or established TLS, repeat potassium, phosphate, calcium, urate and renal function commonly every 4 to 6 hours and more frequently when unstable, adjusting the next intervention to trend rather than one value.
Use continuous ECG for severe hyperkalaemia, calcium symptoms or arrhythmia and monitor capillary glucose for at least 6 hours after insulin-glucose treatment.
Record hourly urine output and cumulative balance, weight and respiratory findings; falling urine with increasing fluid or oxygen need requires immediate renal and critical-care reassessment.
After rasburicase, use chilled urate collection and rapid transport, and continue monitoring for metabolic rebound until tumour response and kidney clearance are stable.
After recovery, document the causative treatment, peak abnormalities, dialysis exposure and revised prevention plan before the next cycle or a more effective line of therapy.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Treatment sensitivity matters

A dramatic response to steroid, antibody or targeted therapy can cause TLS even before conventional chemotherapy begins.

Criteria do not authorise delay

One severe potassium result or symptomatic calcium fall requires treatment although formal laboratory TLS asks for multiple abnormalities.

Allopurinol is preventive

Xanthine oxidase inhibition stops new urate formation but cannot rapidly remove the urate already threatening a high-risk kidney.

Rasburicase alters the specimen

Urate continues to degrade in a warm sample after dosing, creating a falsely reassuring result unless collection and transport remain cold.

Calcium can worsen deposition

During phosphate excess, reserve intravenous calcium for genuine neuromuscular or cardiac danger while phosphate and renal clearance are corrected.

11Common pitfallsFrequent interpretation and management errors.

01
Calling TLS only after chemotherapy and missing spontaneous disease or lysis after steroids, antibodies and targeted agents.
02
Using a normal pretreatment panel to avoid serial monitoring in a biologically high-risk malignancy.
03
Giving allopurinol as though it removes an already high urate concentration.
04
Giving rasburicase without considering G6PD deficiency or sending post-dose urate at room temperature.
05
Correcting asymptomatic hypocalcaemia while phosphate remains high and increasing calcium-phosphate deposition.
06
Using urinary alkalinisation routinely and increasing calcium-phosphate or xanthine precipitation risk.
07
Waiting for refractory uraemia before involving renal medicine despite oliguria, severe phosphate or recurrent potassium rise.