Tumour lysis syndrome

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

Tumour lysis syndrome is a predictable mismatch between malignant-cell breakdown and physiological clearance. It is classically associated with acute leukaemia and high-grade lymphoma, but can follow treatment of bulky, rapidly responsive solid tumours, especially with extensive liver involvement or renal impairment. The trigger may be conventional chemotherapy, corticosteroid, antibody, targeted therapy, radiotherapy or spontaneous tumour turnover. A risk assessment tied to tumour biology is therefore more useful than a list of supposedly safe drug classes.

The characteristic direction is simultaneous rising potassium, phosphate and urate, falling calcium and worsening kidney function. Formal Cairo-Bishop-type criteria help classify laboratory and clinical TLS around treatment, but they are not permission to delay. One severely toxic potassium result or symptomatic low ionised calcium requires treatment before a second criterion appears. Trends matter: a rapid change from a normal baseline can be more dangerous than a static borderline result, and apparent hyperkalaemia in extreme leukocytosis needs urgent non-haemolysed confirmation while ECG toxicity is treated.

Prevention begins before tumour reduction. Correct dehydration, review obstruction and nephrotoxins, choose an appropriately monitored setting and arrange rapid laboratory processing. Isotonic fluid supports renal clearance but must be individualised in heart or kidney disease. Allopurinol inhibits xanthine oxidase and prevents additional urate production, which suits many intermediate-risk situations; it cannot remove urate already present and can allow xanthine accumulation. Rasburicase converts existing uric acid to more soluble allantoin and is used for high-risk or established disease, but G6PD deficiency can lead to haemolysis and methaemoglobinaemia.

Established TLS is managed by treating each threat while continuing control of cell breakdown. Protect the myocardium and shift and remove potassium under the UK Kidney Association algorithm. Stop external phosphate and use renal clearance; severe phosphate burden is often a reason for dialysis. Do not routinely correct asymptomatic hypocalcaemia while phosphate is raised because added calcium can increase precipitation. Give intravenous calcium for seizure, tetany, laryngospasm or electrical danger. Renal referral is early rather than a final step because recurrent potassium, oliguria, fluid overload and phosphate accumulation can require dialysis before traditional uraemic indications.

Key points

TLS is rapid release of tumour-cell potassium, phosphate and nucleic acid; phosphate lowers calcium and purines become urate, threatening heart, brain and kidney.
Risk is determined before treatment from cancer type and sensitivity, burden, LDH, tumour count, baseline urate, renal function, hydration, obstruction and planned therapy.
First-line baseline and serial tests are potassium, phosphate, calcium, urate, creatinine, bicarbonate and LDH with ECG and strict fluid balance when risk is important.
Low-risk patients usually need surveillance and hydration; intermediate risk commonly adds allopurinol; high risk needs monitored hydration, rasburicase and frequent blood tests under the current BSH pathway.
Allopurinol prevents formation of further urate but does not remove existing uric acid; rasburicase rapidly converts existing urate and is preferred for high-risk prophylaxis or established TLS.
Rasburicase is contraindicated in G6PD deficiency because haemolysis and methaemoglobinaemia can occur; post-dose urate samples need pre-chilled tubes and transport on ice.
Do not alkalinise urine routinely, add potassium or phosphate to maintenance fluid, or give calcium merely to normalise an asymptomatic low result while phosphate is high.
Treat severe hyperkalaemia immediately and involve renal medicine early for oliguria, overload, recurrent potassium, severe phosphate or persistent metabolic rebound.

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

Rapid treatment response

Highly chemosensitive leukaemia, lymphoma and selected bulky solid tumours can lose a large cell mass within hours of systemic therapy or corticosteroid exposure.

Large active disease burden

Bulky nodes, extensive liver or marrow involvement, high circulating tumour count and raised LDH increase the intracellular material available for release.

Limited renal reserve

Chronic kidney disease, dehydration, oliguria, obstructive uropathy and nephrotoxic medicines reduce potassium, phosphate and urate clearance during tumour breakdown.

Spontaneous cell turnover

Aggressive untreated malignancy can outgrow its blood supply and lyse spontaneously, producing high urate and kidney injury before anticancer treatment begins.

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

1
Potassium escapes malignant cells
Abrupt intracellular potassium release exceeds renal excretion, changing membrane potential and causing weakness, conduction delay, ventricular arrhythmia or arrest.
2
Phosphate complexes calcium
A large phosphate load lowers ionised calcium and promotes calcium-phosphate precipitation in renal tubules and soft tissue when clearance is inadequate.
3
Purine catabolism raises urate
Released nucleic acid is converted through hypoxanthine and xanthine to uric acid, which can crystallise in acidic, concentrated tubular fluid.
4
Renal injury drives feedback
Urate, calcium-phosphate deposition, hypovolaemia and tumour obstruction reduce filtration, accelerating retention of each toxic electrolyte and worsening overload.

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

High-risk treatment window

Biochemical change can begin before treatment or within hours to days of an effective first dose, including steroid or targeted therapy.

Potassium membrane toxicityRed flag

Weakness, paraesthesia, bradycardia, broad QRS, absent P waves or ventricular arrhythmia is an immediate resuscitation problem.

Symptomatic low ionised calciumRed flag

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

Renal clearance failureRed flag

Oliguria, rising creatinine, hypertension, pulmonary oedema, nausea or encephalopathy signals accumulating solute and fluid burden.

Silent laboratory trajectory

Serial lysis tests may show coordinated metabolic change before symptoms, allowing escalation before an irreversible rhythm or kidney event.

Spontaneous pre-treatment lysis

High urate, LDH and kidney injury in aggressive untreated cancer may represent spontaneous TLS even when phosphate change is less pronounced.

Red flags requiring action

ECG change, muscle weakness, bradycardia or ventricular arrhythmia with rising potassium requires immediate hyperkalaemia treatment before formal TLS criteria are completed.
Tetany, laryngospasm, seizure or QT prolongation with low calcium needs monitored calcium, while asymptomatic hypocalcaemia during high phosphate is usually not corrected.
Falling urine output, rapidly increasing creatinine, pulmonary oedema or biochemical rebound despite urate treatment requires urgent renal replacement discussion.
Bulky, rapidly proliferating and highly treatment-responsive cancer with high LDH or renal impairment needs prophylaxis before steroids, antibodies, targeted therapy or chemotherapy.
TLS can occur spontaneously before treatment or after a first small treatment exposure, so timing alone cannot rule it out.

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 blood panel and ECGFirst stepFirst line
Why
Identify the biochemical syndrome and immediately dangerous electrical effect.
Interpretation and limitations
Measure rapidly processed potassium, phosphate, calcium, urate, creatinine, urea, bicarbonate and LDH; obtain ionised calcium when symptomatic or critically ill.
02
Pre-treatment risk classification
Why
Match location, prophylaxis and monitoring frequency to expected cell death and clearance reserve.
Interpretation and limitations
Combine cancer type, burden, LDH, circulating count, treatment sensitivity and previous response with renal function, urate, hydration, obstruction and nephrotoxins.
03
Serial metabolic trend
Why
Detect early movement and rebound that a single baseline cannot exclude.
Interpretation and limitations
For high risk or established TLS, repeat core chemistry commonly every 4 to 6 hours and more frequently for instability or active hyperkalaemia under the local protocol.
04
Urgent true-potassium confirmation
Why
Separate dangerous hyperkalaemia from haemolysis or leukocyte-fragility artefact.
Interpretation and limitations
Use ECG and a rapidly transported, carefully collected plasma or blood-gas sample; treat credible electrical toxicity without waiting for laboratory adjudication.
05
Fluid and renal assessment
Why
Find oliguria, obstruction and intolerance of preventative hydration.
Interpretation and limitations
Record hourly urine, weight, cumulative balance and respiratory findings and use imaging when tumour or stone obstruction is plausible; creatinine can lag acute loss of clearance.
06
G6PD status before rasburicase
Why
Prevent oxidant haemolysis and methaemoglobinaemia in susceptible patients.
Interpretation and limitations
Check status before planned high-risk prophylaxis; in an immediate emergency, make a senior risk decision informed by ancestry and prior results without ignoring the contraindication.

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

Sepsis with acute kidney injury

Sepsis can cause hypotension, acidosis, oliguria and potassium rise and may coexist during cancer treatment; cultures and antibiotics proceed with lysis management.

Pseudohyperkalaemia

Haemolysis and fragile extreme leukocytosis can artefactually raise laboratory potassium; ECG and an urgently handled plasma or blood-gas sample clarify without delaying true-toxicity treatment.

Rhabdomyolysis or haemolysis

Muscle and red-cell breakdown also release potassium and phosphate; creatine kinase, haemolysis tests, urate pattern and treatment timing help identify overlap.

Drug or renal electrolyte failure

Renin-angiotensin blockade, potassium-sparing therapy, acidosis and pre-existing kidney failure may create hyperkalaemia without the coordinated lysis trajectory.

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

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

1Classify tumour and patient risk from diagnosis, burden, LDH, tumour count, renal reserve, urate, hydration, obstruction and planned treatment.
2Correct volume depletion, stop avoidable nephrotoxins and potassium or phosphate supplements and choose ambulatory, ward or higher-acuity monitoring appropriate to risk.
3Use surveillance and hydration 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 TLSRemove urate and preserve clearancePotassium, phosphate or urate rises with falling calcium or renal function around tumour reduction.

1Call oncology or haematology, renal medicine and critical care, start continuous ECG when indicated and reassess neurological, respiratory, fluid and urine status.
2Give rasburicase when indicated and carefully titrated isotonic fluid without potassium or phosphate, balancing ongoing tumour control against current instability.
3Repeat lysis chemistry at least every 4 to 6 hours and arrange renal replacement early when potassium, phosphate, uraemia or fluid cannot be controlled.

03HyperkalaemiaProtect, shift and remove potassiumSevere potassium, ECG change, muscle weakness or arrhythmia occurs during suspected TLS.

1Follow the UK Kidney Association algorithm, giving intravenous calcium to stabilise the myocardium when ECG toxicity is present with continuous monitoring.
2Give intravenous soluble insulin with glucose and use nebulised salbutamol as an adjunct when appropriate, monitoring glucose for delayed hypoglycaemia.
3Remove potassium by recovering renal excretion or urgent dialysis and recheck early because intracellular shift is temporary while lysis continues.

04Low calciumTreat clinical toxicity rather than a target numberIonised or adjusted calcium falls as phosphate rises during TLS.

1Assess symptoms and ECG and stop non-essential phosphate and calcium delivery while restoring renal phosphate clearance.
2Withhold routine calcium in asymptomatic hypocalcaemia because increasing the calcium-phosphate product can worsen renal and tissue deposition.
3Give monitored intravenous calcium gluconate for seizure, tetany, laryngospasm or arrhythmia while urgently reducing phosphate and arranging renal support.

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

Prevents generation of additional uric acid in many intermediate-risk patients by inhibiting xanthine oxidase.

Allopurinol

Give 300 mg orally once daily, or 100 mg three times daily, commonly starting 24 to 48 hours before tumour-reducing treatment and continuing through the defined lysis-risk period, with renal dose adjustment.

It does not lower urate already present and may increase xanthine load. Stop for serious rash or hypersensitivity and avoid or drastically reduce azathioprine or mercaptopurine because exposure rises.

Rapidly removes existing uric acid for high-risk prophylaxis and established TLS by converting it to soluble allantoin.

Rasburicase

Give rasburicase 0.2 mg/kg intravenously once daily over 30 minutes for up to 7 days, with actual duration determined by risk, tumour response and serial urate under the current BSH and product protocol.

Do not use in G6PD deficiency because severe haemolysis and methaemoglobinaemia can occur. Keep post-dose urate samples cold from collection to analysis to avoid falsely low ex-vivo results.

Temporarily shifts potassium intracellularly while ongoing lysis is controlled and definitive renal removal is organised.

Soluble insulin with glucose for hyperkalaemia

For severe adult hyperkalaemia, give 10 units soluble insulin intravenously with 25 g glucose under the UK Kidney Association algorithm, adding the recommended glucose infusion when pretreatment glucose is below 7 mmol/L.

Check capillary glucose before treatment and serially for at least 6 hours because delayed hypoglycaemia is common; a temporary potassium fall is redistribution, not removal.

Treats dangerous 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 intravenously diluted in 50 to 100 mL of 5% glucose over 10 minutes with continuous ECG monitoring, repeating by symptoms and ionised calcium.

Do not correct asymptomatic hypocalcaemia routinely during marked hyperphosphataemia; avoid extravasation and use specialist caution with digoxin and persistent high calcium-phosphate product.

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

Sudden cardiac death

Potassium toxicity and severe calcium disturbance can cause conduction block, ventricular tachyarrhythmia, fibrillation or pulseless arrest before other lysis symptoms appear.

Neuromuscular calcium toxicity

Reduced ionised calcium causes paraesthesia, cramp, carpopedal spasm, laryngospasm, seizure and electrical instability, especially while phosphate remains high.

Acute kidney failure

Crystal and calcium-phosphate injury, low circulating volume and tumour obstruction can lead to oliguria, uraemia, overload and dialysis.

Cancer-treatment disruption

Metabolic instability and renal failure can interrupt a curative regimen, alter drug clearance and create avoidable mortality from both cancer and treatment.

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

Before therapy, record tumour and patient risk, potassium, phosphate, calcium, urate, creatinine, bicarbonate, LDH, weight, fluid status and planned monitoring location.
In high-risk or established TLS, repeat core lysis chemistry commonly every 4 to 6 hours and shorten the interval for unstable potassium or renal decline.
Use continuous ECG for severe hyperkalaemia, calcium symptoms or arrhythmia and check capillary glucose for at least 6 hours after insulin-glucose treatment.
Measure hourly urine and cumulative balance and reassess weight and lungs; oliguria with rising fluid or oxygen need triggers immediate renal escalation.
After rasburicase, use pre-chilled urate collection and rapid cold transport and continue testing until metabolic rebound is no longer plausible.
Before the next cancer cycle, document the trigger, maximum abnormalities, dialysis exposure and an upgraded prevention plan.

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

Biology outranks drug label

Any intervention that kills a large responsive tumour mass rapidly can provoke TLS, including steroid, antibody, small molecule and radiotherapy.

One lethal result is enough

Formal classifications support communication, but severe hyperkalaemia or symptomatic hypocalcaemia is treated before additional criteria accumulate.

Allopurinol cannot clear urate

Xanthine oxidase inhibition is preventive; established high urate needs a removal strategy rather than simply more allopurinol.

The sample remains enzymatic

Rasburicase continues degrading urate after blood is drawn unless the specimen stays chilled, creating falsely reassuring laboratory values.

Dialysis can be early

Recurrent potassium, severe phosphate or overload may justify renal replacement before conventional late uraemic thresholds are met.

11Common pitfallsFrequent interpretation and management errors.

01
Considering TLS only after conventional chemotherapy and missing spontaneous lysis or response to steroid and targeted treatment.
02
Using one normal baseline to avoid serial tests in a biologically high-risk cancer.
03
Giving allopurinol as though it rapidly removes an already elevated urate.
04
Giving rasburicase without assessing G6PD risk or transporting subsequent urate samples warm.
05
Correcting asymptomatic low calcium while phosphate is markedly high.
06
Using urinary alkalinisation routinely and increasing calcium-phosphate or xanthine precipitation risk.
07
Waiting for refractory uraemia before involving renal medicine despite recurrent potassium, oliguria or overload.