Allopurinol nephrolithiasis

Patients with recurrent attacks, evidence of tophi or joint destruction, or uric acid nephrolithiasis are candidates for maintenance therapy with allopurinol or probenecid to lower serum uric add levels. 

Since allopurinol blocks xanthine conversion to uric acid, urinary xanthine excretion is increased, creating a risk of xanthine crystal formation in the urinary system or even in muscles this can result in nephrolithiasis (12). It is still an open question whether a predisposition to renal disease or renal disease itself is required to precipitate these adverse effects. It is also not known whether increased excretion of orotic acid, due to an interaction of allopurinol with pyrimidine formation, has any consequences for these adverse effects or for its role in reducing glucose tolerance. 

The mainstay of drug therapy for recurrent uric acid lithiasis is allopurinol. It is effective in reducing both serum and urinary uric acid levels, thus preventing the formation of calculi. Allopurinol is also recommended as prophylactic treatment in patients who wfll receive cytotoxic agents for the treatment of lymphoma or leukemia. The marked increase in uric acid production associated with cytolysis of a neoplasm predisposes a patient to the development of uric acid nephrolithiasis. 

The clinical manifestations of gout, i.e. articular and renal disease, are intimately connected with hyperuricemia and/or particularities of renal handling of uric acid. It is well established that normalization of plasma uric levels will cure the joint disease. The diminution of renal uric acid excretion by administration of allopurinol will cure nephrolithiasis in its uncomplicated forms. One may presume that the other manifestations of the gouty kidney (i.e. parenchymal renal disease, hypertension and azotemia) will also be influenced by a therapy reducing urinary uric acid however no reliable reports exist as yet on this point. 

In the therapeutic treatment of gout and urate nephrolithiasis with allopurinol, xanthine and hypoxanthine are eliminated instead of uric acid as end-products of purine metabolism. A good separation of these compounds from each other and from uric acid is possible using TLC [21] their increase in urine is proof that the therapy is being observed. 

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