rasburicase
Meaning of rasburicase: A manufactured copy of an enzyme humans lost during evolution, given to strip uric acid out of the blood within hours.
Definition of rasburicase
Rasburicase is a manufactured enzyme that breaks uric acid down into allantoin, a substance the kidneys clear far more easily. It is given by drip to lower dangerously high uric acid levels, most often when a large cancer breaks apart rapidly at the start of treatment and floods the blood with the contents of dying cells. The effect appears within hours.
Why does uric acid build up during cancer treatment?
Cells that die release their DNA, which is broken down into purines and finally into uric acid. When a bulky leukemia or lymphoma collapses over a day or two, that release overwhelms the kidneys. Uric acid crystals block the tubules, and potassium and phosphate released at the same time disturb the heart rhythm and bind calcium. The combination is called tumor lysis syndrome, and kidney failure is its most common serious consequence.
How does it differ from allopurinol?
| Drug | What it does | Effect on uric acid already present |
|---|---|---|
| Allopurinol | Blocks the enzyme that makes uric acid | None, so levels fall only as the kidneys excrete it |
| Rasburicase | Destroys uric acid directly | Levels drop steeply within hours |
Why does the body not make it already?
Most mammals carry an enzyme called urate oxidase that converts uric acid into allantoin. The gene for it is present in humans but broken, so uric acid is the end of the line and it circulates at levels far higher than in other species. Rasburicase is a recombinant version of the fungal enzyme, meaning it is produced by cells given the gene in the laboratory rather than extracted from tissue.
What limits its use?
Splitting uric acid generates hydrogen peroxide. Red cells normally neutralize it, but in people with G6PD deficiency they cannot, so the cells break apart and the blood pigment is altered into a form that carries oxygen poorly. Because the enzyme is a foreign protein, allergic reactions occur and antibodies against it can develop, blunting the response to a later course. There is also a laboratory trap. The enzyme keeps working inside a collected blood tube, so a sample left at room temperature reports a uric acid level far lower than the patient actually has.
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Used in a sentence
Rasburicase was given for tumor lysis syndrome after the uric acid level rose sharply following induction chemotherapy.
Good to know
Rasburicase causes red blood cell breakdown in people with G6PD deficiency, and it continues to destroy uric acid inside a collected blood tube, so a sample kept warm reads falsely low.