A 34-year-old male, who was previously well, has been admitted to your ICU with vomiting, malaise and oliguria. He has a new diagnosis of diffuse large B cell lymphoma and received his first round of chemotherapy four days ago. The following blood results were obtained:

Parameter   Patient Value Adult Normal Range
Sodium 138 mmol/L    - 135 - 145
Potassium 6.2 mmol/L* 3.5 - 5.0
Bicarbonate 17.0 mmol/L* 22.0 - 26 .0
Urea 21.0 mmol/L* 3.0 - 8.0
Creatinine 398 µmol/L* 45 - 90
Glucose 5.3 mmol/L 3.5 - 6.0
Magnesium 1.10 mmol/L*  it- 0.75 - 0.95
Calcium corrected 1.78 mmol/L* 2.12 - 2.62
Phosphate 3.9 mmol/L*   "t- 0.8 - 1.5
Urate   10 mmol/L 0.20 - 0.42

a) List a differential diagnosis for the kidney injury. (20% marks)

b) Outline your assessment and management of this patient. (80% marks)

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College answer

    a)                                                         
It is likely the patient has tumour lysis syndrome (10/20). 
 
Other differentials of acute kidney injury should be considered turn into list 
•    pre-renal (e.g. hypovolaemia, reduced perfusion) 
•    renal (e.g. glomerulonephritis, interstitial nephritis, vasculitis, ATN, acute cortical necrosis, drugs, pyelonephritis) 
•    post-renal (e.g. obstruction for calculi, tumour, clot) 
•    Chronic kidney injury which would put the patient at greater risk of tumour lysis is possible, but not likely if he is previously well.  
•    Sepsis is possible although it would usually occur at a later stage  
 
(Marking Guide: 1 Mark for TLS; 0.25 marks for each reasonable differential) 
 
    b)                                                     
Resuscitation as needed to ensure adequate oxygenation and tissue perfusion. 
 
Exclude differential diagnoses (history, examination and investigation including renal ultrasound). 
•    ECG, and if ECG changes consistent with hyperkalaemia, consider early intervention with (1) CaCl2 or Ca gluconate for temporary ECG stabilisation (new broad QRS or arrhythmia) 
•    (2) shift K intracellularly with either B2 agonist therapy (e.g. ventolin neb), insulin dextrose, or NaHCO3 if indicated 
 
Specific management of tumour lysis syndrome 
•    IV fluids to encourage a diuresis  
•    Once well hydrated diuretics could be considered to encourage a diuresis (frusemide is most widely used, acetazolamide may alkalinise the urine which will increase the solubility of uric acid but reduce the solubility of CaPO4 and hence is less widely used) 
•    Rasburicase (to break down uric acid) o Urine alkalinisation not recommended if rasburicase has been given 
o If rasburicase not available allopurinol maybe given (however, this is not as effective and will not breakdown uric acid, it merely reduces further uric acid formation) 
 
Haemodialysis and/or filtration is generally instituted for standard indications, although it maybe instituted earlier in tumour lysis syndrome or if the patient remains oliguric. 
      
Treat hypocalaemia only if symptomatic (cramps, paraesthesia) as excessive Ca replacement may precipitate CaPO4. 
      
Hyperphosphataemia is most efficiently treated with haemodialysis and/or filtration, insulin dextrose and oral phosphate binders have a limited role. 
      
Seek and treat sepsis. 
      
Consider excluding renal obstruction with US. 
 
Routine supportive care 
Optimise oxygenation (if fluid overloaded maybe need supplemental oxygen) 
Optimise perfusion and blood pressure 
Withhold nephrotoxic medications drugs (NSAIDS, ACE-I, ARBs) 
Consider dose modification of renally excreted drugs 
DVT prophylaxis 
Single room/ neutropenic precautions 
 

Discussion

The college certainly seems to love tumour lysis syndrome. This is the fourth time it has come up in the exam. It is certainly the top differential in this context. Nothing else could ever give rise to a urate level of 10mmol/L. 

The list of other differentials might include:

  • Nephrotoxicity from chemotherapy agents
  • Sepsis
  • Dehydration
  • Hyperproteinaemia (i.e hyperviscosity syndrome)
  • Renal vein thrombosis 
  • Renal vascular supply compression by para-aortic lymphadenopathy
  • Infiltration by tumour

And there is no reason why all of these might not co-exist simultaneously.

Assessment will consist of:

  • History
    • Time course of the symptoms
    • History of oral intake
    • Changes in urine colour and volume
    • Fevers
    • Pain
    • Other background history
    • History of recent medication use, eg. NSAIDs, ACE-inhibitors etc
  • Examination:
    • Hydration status
    • Haemodynamic parameters, i.e. looking for septic shock
    • Organomegaly
    • Lymph nodes
    • Renal angle tenderness
    • Temperature
    • Gouty joints
  • Investigations
    • Urinalysis looking for myoglobinuria
    • Blood count looking for WCC 
    • Biochemistry looking for protein levels
    • Coags and platelet count looking for coagulopathy (as the patient may require a vas cath)

Specific management will consist of:

  • Rehydration and forced diuresis
    • Balanced crystalloid infusion, to help correct acidosis
    • Frusemide infusion to encourage diuresis
  • Management of hyperuricaemia and other electrolyte abnormalities
    • Rasburicase 
    • Calcium gluconate as cardioprotective agent
    • Insulin and dextrose in order to correct hyperkalemia
  • Management of acute kidney injury
    • Observe for improvement with rehydration and forced diuresis (AKI may resolve over the subsequent days)
    • If oliguria does not resolve or other criteria for urgent dialysis are met, obtain vascular access for CRRT and commence CVVHDF.

References

References

Tiu, Ramon V., et al. "Tumor lysis syndrome." Seminars in thrombosis and hemostasis. Vol. 33. No. 4. New York: Stratton Intercontinental Medical Book Corporation, c1974-, 2007.

Howard, Scott C., Deborah P. Jones, and Ching-Hon Pui. "The tumor lysis syndrome." New England Journal of Medicine 364.19 (2011): 1844-1854.

Cairo, Mitchell S., and Michael Bishop. "Tumour lysis syndrome: new therapeutic strategies and classification." British journal of haematology 127.1 (2004): 3-11.