Urate oxidases

Uratoxidase is an enzyme that is able to oxidize uric acid into water-soluble allantoin (Stalla 2007). Uratoxidase lowers uric acid levels much more rapidly than allopurinol (Kuhlmann 2015). Most mammals are able to metabolize uric acid to allantoin. However, humans do not have this enzyme.

For therapeutic purposes, uricase is isolated from Aspergillus flavus (Dingermann 2013).

Due to the above-described properties, urate oxidase is used medicinally as "rasburicase" (trade name Fasturtec R® )(Herold 2021). Rasburicase is recommended in tumor lysis syndrome - despite the lack of studies - in first-line therapy (Kuhlmann 2015).

Indications:

• For prophylaxis of acute renal failurein aggressively growing lymphomas before or during chemotherapy (Kuhlmann 2015).
• Tumor lysis syndrome

Tumor lysis syndrome is a potentially life-threatening clinical picture that can develop spontaneously in fast-growing tumors or during therapy and results from rapid cell decay (apoptosis).

Laboratory chemical changes include:

• Hyperkalemia (25% of baseline or ≥ 6.0 mmol / l [Kuhlmann 2015]).
• Hyperuricemia (25 % of baseline or ≥ 8.0 mg / dl [Kuhlmann 2015])
• Hyperphosphatemia (25% of baseline or ≥ 1.45 mmol / l [Kuhlmann 2015])
• Secondary hypocalcaemia (25% decrease from baseline or ≤ 1.75 mmol / l [Kuhlmann 2015]).

Clinical symptoms include cardiac arrhythmias (due to hyperkalemia [Kuhlmann 2015]), convulsions, acute renal failure (Neuendorff 2020).

Side effects:

• allergic reactions to the ingredients
• Induction of antibodies to the ingredients (Herold 2021).

Contraindications:

• Allergies to the ingredients
• glucose- 6- phosphate- dehydrogenase deficiency
• Diseases that may also lead to hemolytic anemia (Aktories 2017).

Application: Rasburicase is injected i. v. only. The onset of action is relatively rapid and is a few hours. The duration of efficacy is 10 h (Herold 2021).

Dosage: Dosage recommendation 0.15 - 0.20 mg / kg bw i. v. in combination with i. v. hydration (Kuhlmann 2015).

Serum samples for uric acid should be sent refrigerated for patients treated with urate oxidases (otherwise the enzymatic reaction continues in vitro and falsifies the result).

1. Aktories K et al. General and special pharmacology and toxicology. Elsevier Urban and Fischer Publishers 527
2. Dingermann T et al (2013) Pharmaceutical biology: molecular basis and clinical application. Springer Verlag 206 - 207
3. Herold G et al (2021) Internal medicine. Herold Publishers 708
4. Kuhlmann U et al (2015) Nephrology: pathophysiology - clinic - renal replacement procedures. Thieme Verlag 210
5. Neuendorff N R (2020) Tumor lysis syndrome in: Jäger D et al (2020) Onco- Nephrology. Springer Verlag 243 - 252
6. Stalla G K (2007) Therapy encyclopedia endocrinology and metabolic diseases. Springer Verlag 1168