Cancer Hyperuricemia

While purine deficiency states are rare in human subjects, there are numerous genetic disorders of purine catabolism. Hyperuricemias may be differentiated based on whether patients excrete normal or excessive quantities of total urates. Some hyperuricemias reflect specific en2yme defects. Others are secondary to diseases such as cancer or psoriasis that enhance tissue turnover. 

Uric acid excretion is reduced in patients with chronic kidney disease, putting them at risk for hyperuricemia. In patients with persistently acidic urine and hyperuricemia, uric acid nephrolithiasis can occur in up to 25% of patients in severe cases, uric acid stones can cause nephropathy and renal failure. Extreme hyperuricemia can occur because of rapid tumor cell destruction in patients undergoing chemotherapy for certain types of cancer (see Chap. 85). 

The anticancer drug 6-mercaptopurine is deactivated by the enzyme xanthine oxidase. A cancer patient being treated with 6-meicaptopurine develops hyperuricemia, and the physician decides to give the patient allopurinoL... 

Secondary hyperuricemia may be caused by other diseases, for example, cancer, chronic renal insufficiency, etc. 

Mercaptopurine and thioguanine are both given orally (Table 55-3) and excreted mainly in the urine. However, 6-MP is converted to an inactive metabolite (6-thiouric acid) by an oxidation catalyzed by xanthine oxidase, whereas 6-TG requires deamination before it is metabolized by this enzyme. This factor is important because the purine analog allopurinol, a potent xanthine oxidase inhibitor, is frequently used with chemotherapy in hematologic cancers to prevent hyperuricemia after tumor cell lysis. It does this by blocking purine oxidation, allowing excretion of cellular purines that are relatively more soluble than uric acid. Nephrotoxicity and acute gout produced by excessive uric acid are thereby prevented. Simultaneous therapy with allopurinol and 6-MP results in excessive toxicity unless the dose of mercaptopurine is reduced to 25% of the usual level. This effect does not occur with 6-TG, which can be used in full doses with allopurinol. 

Allopurinol is used in the treatment of hyperuricemia, which is associated with chronic gout and in cancer chemotherapy. Allopurinol has been used in renal calculi caused by the deposition of calcium oxalate and of 2,8-dihydroxy-adenine. Allopurinol treatment does cause hypersensitivity reaction, which may be fatal. 

Aotino Add Supplemenis Complementary Proteins Clinical Issues In Protein Nutrition Modifib. d Tasting Chronic Renal Failure Hyperuricemia Wasting in Cancer and AIDS References Bibliography... 

Bosly A, Sonet A, Pinkerton CR, et al. Rasburicase (recombinant urate oxidase) for the management of hyperuricemia in patients with cancer report of an international compassionate use study. Cancer 2003 98 1048-1054. 

Secondary (or acquired) gout is caused by seemingly unrelated disorders. These conditions may cause hyperuricemia by either overproduction of uric acid or its undersecretion by the kidneys. For example, leukemia patients overproduce uric acid either because of massive cell destruction or the chemotherapy treatment required to destroy the cancerous cells. Hyperuricemia also results when certain drugs interfere with the renal secretion of uric acid into the urine. Patients with lead poisoning are also likely to develop gout because of renal damage. 

Allopurinol is used not only in treating the hyperuricemia associated with gout but also in the secondary hyperuricemia associated with the use of antineoplastic agents. Therefore, allopurinol may be used in the management of patients with leukemia, lymphoma, and solid tumor malignancies who are receiving cancer therapy that causes elevations of serum and urinary uric acid levels. Allopurinol may interfere with the metabolism of antineoplastic agents such as azathioprine and 6-mercaptopurine. 

If allopurinol is used adjunctively in cancer chemotherapy to offset hyperuricemia, the dosage of this drug should be reduced to 25% of normal. 

Several enzyme therapies are also used in the treatment of cancer. For instance, rasburicase (uricase Elitek EC 1.7.3.3) is used in the treatment of hyperuricemia due to tumor lysis syndrome (TLS). This is a potentially life-threatening condition that is associated with rapidly developing tumors, such as those found in lymphoma and leukemia, in patients undergoing chemotherapy. The incidence of hyperuricemia in these patients is close to 20% [88]. Uricase is an interesting enzyme, because it is found in most mammals, with the exception of humans, where the gene contains a nonsense mutation [89]. Rasburicase is well tolerated, has a very fast onset of action, and is administered intravenously once a day. However, the enzyme cannot be used on patients with glucose-6-phosphate dehydrogenase deficiency [90]. The... 

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