Timor lysis Syndrome

Question 1

Definition and key Metabolic changes

Answer 1

Key Metabolic Changes:

A constellation of biochemical abnormalities triggered by rapid tumor cell lysis.

*	Hyperkalemia
*	Hyperphosphatemia
*	Hypocalcemia
*	Hyperuricemia

Question 2

Pathophysiology
&
Mech of Drugs used

Answer 2

Allopurinol:

->Tumor lysis → release of purine metabolites → hypoxanthine → converted by xanthine oxidase to:
* Xanthine (nephrotoxic)
* Uric acid (more nephrotoxic)

->* Progressive renal failure - due to accumulation of phosphate, uric acid, and xanthine in renal tubules
* May require dialysis to break the cycle

*	Inhibits xanthine oxidase (↓ uric acid formation)
*	May ↑ xanthine levels (also nephrotoxic)

*	Converts uric acid to allantoin (non-toxic, water soluble)   *Can act on uric acid which has already been generated.
*	Effective for rapid urate lowering
*	Not useful if uric acid has already crystallized

Allen+tony- allentoin

Question 3

Renal Failure in TLS

Answer 3

Pathophysiology
* Due to deposition of CaPO₄ and uric acid in renal tubules → can lead to hypocalcemia.
*Despite hypocalcemia, Ca supp. usually not advisable–>increases CaPo4 deposition

Question 4

Timing and Risk Factors

Answer 4

Tumor-related:

Timing
* Occurs usually 1–5 days after chemotherapy or radiotherapy initiation.

⸻

Risk Factors
# Pre-existing metabolic abnormalities:
* High LDH (>2500 IU/L)
* Hyperphosphatemia
* Hyperuricemia
* Pre-existing renal failure
* Dehydration
* Gout

*	Large tumor mass or high tumor burden
*	High proliferative index
*	Marrow infiltration
*	Organ infiltration
*	Highly chemosensitive tumors (e.g. Burkitt’s lymphoma, acute leukemias)

*	High-intensity chemotherapy (e.g. Napharubicin)

Question 5

Symptoms

Answer 5

Symptoms
* ↓ Calcium–> * Tetany, seizures
* ↑ Potassium–>Arrhythmias
* ↑ Uric acid–> Oliguric renal failure

Question 6

Invx

Answer 6

Investigations
* Electrolytes (K⁺, Ca²⁺, PO₄³⁻, uric acid)
* Renal function (U/E, Cr)
* Urine microscopy: urate crystals

Question 7

D/Dx

Answer 7

Pseudohyperkalemia:

*	Caused by hemolysis, high WBC count, or poor venepuncture technique. #	Other differentials:
*	Rhabdomyolysis
*	Crush injury
*	Hemolysis
*	Acute tubular necrosis (ATN)

Question 8

Prevention

Answer 8

Prevention
1> Identify at-risk patients
2>Hydration: maintain UOP ≥ 1–1.5 mL/kg/hr
* IV fluids to maintain euvolemia and prevent fluid overload
3> > Monitor urate levels closely
Urate-lowering agents:
* Allopurinol: inhibits xanthine oxidase
4> Avoid nephrotoxic drugs: especially calcium-containing fluids, ACE inhibitors, NSAIDs
5> Monitor electrolytes: calcium, phosphate, potassium

Question 9

Treatment

Answer 9

Supportive:

Treatment: Specific:
1. Rasburicase:
* Dose: 0.2 mg/kg/day for up to 5 days
* Contraindicated in:
-G6PD deficiency-> Hemolysis risk
-Methemoglobinemia
-Allergy to rasburicase

2.	Allopurinol:
*	May reduce efficacy of rasburicase → avoid co-administration

1. Hydration
   
   • Adequate hydration (IV fluids)
   • Use balanced crystalloids (avoid excess chloride)
   • IV rate: 150–200 mL/hr to maintain UOP >100 mL/hr
     . If poor urine output (UOP)
   • Trial of diuretics: furosemide, thiazides
   • Note: forced diuresis is not proven to be beneficial
   2* Renal diet
   Restrict potassium (K⁺) and phosphate (PO₄³⁻) intake
   3. Management of Hyperkalemia
   4* Avoid acetazolamide5* Urinary alkalinisation: promotes precipitation of calcium-phosphate and uric acid crystals
   * Risk of calcium phosphate nephropathy
   6. Hypocalcemia-ignore if possible
      * Treat if symptomatic or PO₄³⁻ is high
      * Dialysis may be needed in refractory cases
   7. Dialysis
      * If:
      * UOP remains low
      * Worsening acidosis
      * Uncontrolled hyperkalemia or hyperphosphatemia
      * Symptomatic hypocalcemia
      * Uric acid crystal nephropathy
      * Fluid overload
2. Uric acid measurements:
   
   • Can be artificially low if rasburicase degrades uric acid in vitro
   • Use special tubes (pre-chilled, sent on ice) to prevent in vitro degradation