Tumor lysis in renal cell carcinoma

Doing a morning report on RCC on being treated with Sunitinib lead to AKI.

What is Sunitinib?
A molecule(not antibody) which inhibits multiple tyrosine kinase motifs of second messenger systems of chemokines like VEGF.

It has some crazy side effects like

1) Hypothyroidism
2) Cardiac failure
3) HTN/Proteiuria a.k.a Bevacizumab like
4) Pancreatitis

Only one report of TLS

Coming to TLS

Criteria does not have creatinine!!!

Has uric acid>8
potassium>6
Calcium< 7
Phosphate> 4.5

If preexisting abnormalities in the above values due to some other pathologies take a 25% change.

If cr >1.5x of previous it becomes clinical TLS

TLS most commonly happens in rapidly proliferating tumors.
Why?
They need all the purines for the DNA/RNA for them to grow and when it breaks down as we all know what we get is uric acid

Rapidly proliferating leukemias and lymphomas are the ones at highest risk

TLS happens within 48 hrs of chemo and anything beyond is unlikely from TLS

Why do the electrolyte changes happen?

Potassium is intracellular and when the chemo lyses the cell it comes out
same applies to phosphate/urate

calcium goes down due to phosphate binding with it

How is the kidney affected?

Uric acid precipitates and blocks up the nephrons

What do we do about TLS
1) Prevent it by
   - IV fluids - keep the uric acid low in concentration in the kidney
   - Allopurinol - only useful preemptive and does not prevent xanthine and hypoxanthine from precipitating!
   - Uricase - melt the uric acid simple

Bicarbonate is unproven as it will make uric acid soluble but calcium phosphate insoluble:(

2)Treat
    - HD - Takes out uric acid
    - Uricase