Nephrotoxicity allopurinol

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. 

Calcium channel blockers and prostaglandins have been used to reduce the nephrotoxic effects of cyclosporin during kidney transplantation.201 Interleukin-2 should be taken cautiously when coadministered with NSAIDs.202 Coadministration of tamoxifen with allopurinol and anticoagulants should be monitored carefully.203... 

Assis SM, Monteiro JL, Seguro AC. L-Arginine and allopurinol protect against cyclosporine nephrotoxicity.Transplantation 1997 63 1070-1073. 

The ciclosporin levels of a kidney transplant patient rose by about threefold, accompanied by an increase in serum creatinine from 124 to 194 micromol/L, after allopurinol 100 mg daily was taken for 12 days. Another previously stable kidney transplant patient had a two- to threefold rise in her ciclosporin level when allopurinol 200 mg daily was given. Her serum creatinine remained unchang throughout. The general importance of these two reports of increased ciclosporin levels is unknown, although increases in ciclosporin levels are associated with increased risk of nephrotoxicity. 

The prognosis in APRT deficiency clearly depends on the renal function at the time of diagnosis. This underlines the importance of early recognition and appropriate treatment. Allopurinol, — without alkali— will inhibit the formation of the nephrotoxic 2,8-DHA, and thus effectively prevent what should be an essentially benign disorder becoming a potentially lethal one. The long-term effect of allopurinol therapy with its potential for adenine accumulation, particularly in those cases with severe renal damage, remains to be established. All supposed uric acid stones should be submitted for analysis by special techniques to avoid any further confusion in the future. 

Allopurinol (50 mg/kg subcutaneously for 5 days) potentiated cisplatin-induced nephrotoxicity in rats (EROiNg et al. 2000). 

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