Overview

Tumour Lysis syndrome (TLS) is a life-threatening condition which occurs when cancer cells break down rapidly, causing contents inside the cell to be released into the bloodstream, leading to toxicity. This process occurs more rapidly than your body can eliminate them.  Patients must note that early identification and treatment are key for favourable clinical outcomes.

What is tumour lysis syndrome?

TLS is a group of conditions that can affect your heart, kidneys and muscles. TLS occurs within hours of cancer treatment and often develops rapidly under pressure from chemotherapy, potentially becoming a medical emergency. While it typically arises within the first week of chemotherapy, it can also occur without chemotherapy in rare occurrences, referred to as spontaneous TLS.¹

Kidney-related manifestations

• Hyperuricemia (high uric acid): high uric acid can deposit uric acid crystals in your kidneys, causing kidney dysfunction and failure
• Hyperphosphatemia (high phosphorus): high phosphorus levels affect your kidney function
• Uremia: When your kidneys stop filtering toxins from your blood. Uremia causes serious bone, muscle, heart and blood vessel issues

Cancers commonly associated with  TLS include: 

• Acute lymphocytic leukaemia 
• Aggressive non-Hodgkin’s lymphoma 
• Acute Myeloid Leukaemia (AML)
• B-cell acute lymphoblastic leukaemia (ALL)
• Small cell lung cancer 

Cancers that are ess commonly associated with TLS

• Breast cancer 
• Neuroblastoma 

Factors which can increase the risk of TLS

• High white blood cell count 
• High blood uric acid level 
• Kidney problems 
• Dehydration 
• Large tumours

How TLS affects the kidneys

1. Hyperuricemia (High Uric Acid Levels)

The breakdown of nucleic acids from lysed tumour cells leads to excessive uric acid production. Uric acid is poorly soluble in acidic urine and can crystallise, leading to nephropathy and kidney damage.

2. Hyperphosphatemia (High Phosphate Levels)

Tumour cells have excessive amounts of phosphorus present in them. When these cells die, they release phosphorus, which can bind with calcium to form calcium phosphate crystals. These crystals can deposit in the kidney tubules, leading to nephrocalcinosis (calcium phosphate deposition), which can lead to acute kidney damage.

3. Hypocalcemia (Low Calcium Levels)

Due to phosphate binding to calcium, free calcium levels drop in the blood, impairing kidney function.

4. Hyperkalemia (High Potassium Levels)

Tumour cells also contain high potassium levels, which are released into the blood upon cell breakdown. The kidneys usually excrete potassium through urine, maintaining electrolyte balance, however, excess levels of potassium can lead to acute kidney injury. 

Symptoms of kidney dysfunction in TLS

Symptoms of TLS usually consist of 

• Nausea 
• Vomiting 
• Diarrhea
• Cardiac Arrhythmias 
• Changes in how much urine you can produce 
• Weakness and lethargy
• Seizures 
• Muscle cramps 

If you have any of these symptoms, please contact your health provider immediately to get them checked.

Management and Treatment

Hydration and hypouricemic therapy (aims to reduce uric acid levels) are the key fundamentals required to manage patients who are at risk for TLS.²

• Hydration

Intravenous hydration is used to increase urine flow and improve toxin filtration in the kidneys. Volumes of urine should be closely monitored. To reduce the levels of hypercalcemia and hyperkalemia, external sources of calcium and potassium must be stopped.

Diuretics can also be recommended to increase how often you urinate.

• Medication

Allopurinol is provided to prevent hyperuricemia by reducing uric acid production. It is used for patients who are at intermediate risk for TLS.

Rasburicase is recommended for high-risk patients or patients who have impaired renal function. It works by breaking down uric acid into a more soluble form for excretion.

• Management of other electrolyte abnormalities includes:
  • Hyperkalemia: Potassium levels in the blood must be monitored every 4-6 hours, and potassium intake must be avoided
  • Hyperphosphatemia: Monitoring of blood phosphate every 4-6 hours and intake of any phosphate must be avoided
  • Hypocalcemia - Phosphate binder therapy is used to reduce serum phosphate levels and prevent the formation of calcium phosphate

Summary

TLS is a life-threatening condition that can severely impact kidney function due to the rapid breakdown of cancer cells. The release of toxic cellular contents such as uric acid, phosphate, and potassium can overwhelm the kidneys, leading to acute kidney injury. Early recognition of TLS  symptoms,  such as reduced urine output and nausea, is crucial for timely intervention. Effective management through hydration and medications can help prevent severe complications. Understanding TLS and its effect on the kidneys empowers patients and caregivers to take proactive steps, ensuring better health and reducing the risk of kidney failure.