Urinary-Tract Stones Resulting from the Excretion of Oxypurinol

Landgrebe, Albert R.; Nyhan, William L.; Coleman, Mary

doi:10.1056/nejm197503202921208

Cited by 48 publications

(13 citation statements)

References 7 publications

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“…Secondly the serum levels of purine precursors, xanthine and hypoxanthine, are increased (DeConti and Calabresi, 1966;Spector, 1977). As xanthine is less soluble in urine as compared to uric acid, xanthine nephropathy resulting in acute obstructive uropathy may develop (Band et al, 1970;Landgrebe et al, 1975). Yet another drawback is that it is known to interfere with the degradation of other purines such as 6-mercaptopurine (6-MP) and azathioprine through inhibition of the p450 pathway.…”

Section: Treatment With Allopurinol and Rasburicasementioning

confidence: 99%

Tumour Lysis Syndrome: Implications for Cancer Therapy

Mika¹,

Ahmad²,

Guruvayoorappan³

2012

Asian Pacific Journal of Cancer Prevention

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Asian Pacific J Cancer Prev, 13, 3555-3560 IntroductionTumour lysis syndrome (TLS) is the development of an array of metabolic disturbances that may occur either spontaneously or in response to cancer therapies. It results when a huge number of rapidly dividing cancer cells, particularly leukemia and lymphoma, are killed or lysed by cytotoxic therapy such as chemotherapy and radiation. Normal intracellular components of cells include potassium, phosphorus and nucleic acids. These intracellular ions are present in large amounts in cancer cells as compared to those in normal cells.When malignant cells are killed by therapy they release their contents into the systemic circulation, which accumulate faster in the body than being eliminated from the body and the body's homeostatic mechanisms find it difficult to cope with. The release of these intracellular contents cause metabolic disturbances, which in turn manifest into life threatening complications such as hyperkalemia, hyperphosphotemia, hypocalcemia and hyperuricemia. Tumour lysis also releases cytokines that cause a systemic inflammatory response syndrome and often multiorgan failure (Hijiya et al., 2005;Nakamura et al., 2009;Soares et al., 2009).During the early stages, some patients do not experience any symptoms of TLS but have abnormal laboratory values, which is suggestive of its succession. Laboratory results will show high potassium, uric acid and phosphorus levels and low calcium levels in the blood.

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Section: Treatment With Allopurinol and Rasburicasementioning

confidence: 99%

Tumour Lysis Syndrome: Implications for Cancer Therapy

Mika¹,

Ahmad²,

Guruvayoorappan³

2012

Asian Pacific Journal of Cancer Prevention

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“…Urinary oxypurine excretion increases signi fi cantly in the presence of allopurinol, and the relative insolubility of the increments in serum xanthine levels may cause xanthine renal calculi or crystalluria. Oxypurinol has also been identi fi ed with renal stones and urinary tract sludge in rare patients [ 646,647 ] . The dioxygen oxidative product of allopurinol, oxypurinol, is also insoluble and has been demonstrated along with hypoxanthine and xanthine in muscle biopsy specimens from patients treated with allopurinol after its initial release as a therapeutic agent [ 648 ] .…”

Section: Allopurinolmentioning

confidence: 99%

Management of Hyperuricemia and Gout

Newcombe¹

2012

Gout

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“…Its primary metabolite, oxypurinol, is renally eliminated and is poorly soluble at acidic pH [3,65].…”

Section: Miscellaneousmentioning

confidence: 99%

“…Though not seen at the typical doses used in gouty arthritis, nephrolithiasis composed of either oxypurinol or a mixture of xanthine and oxypurinol occur in high-dose allopurinol usage (600-900 mg/day) sometimes required in the inherited metabolic disorder, Lesch-Nyhan syndrome [65][66][67]. Major preventive strategies include alkalinizing the urine and utilizing the lowest effective dose possible.…”

Section: Miscellaneousmentioning

confidence: 99%

Miscellaneous Stone Types

Cutrell

Reilly

2011

Clinic Rev Bone Miner Metab

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Drug-induced calculi and other rare stone types, such as ammonium acid urate or protein matrix stones, represent only about 2% of all renal calculi. However, the chance to easily reverse stone formation risk by discontinuing the offending drug makes identification of these entities important for clinicians. Additionally, study of these rare stone types contributes to understanding the biochemistry of stone formation. Drug-induced calculi may be classified into two groups based on the mechanism of stone formation. The first group includes drugs that provoke calculi composed of principally the drug and its metabolites. These medications tend to be poorly soluble, highly excreted in urine, and required at high dosages for long durations of therapy. Historically, sulfonamides, triamterene, and the HIV protease inhibitor indinavir were leading causes of drug-induced calculi. Uses of novel agents within these drug classes or alternative therapies have reduced the incidence attributed to these drugs, although risk from newer, commonly used medications-notably ciprofloxacin, aminopenicillins, ceftriaxone, ephedrine, and guaifenesinare increasingly being recognized. Microscopic analysis for crystalluria or infrared spectroscopy of collected stones aid in recognition of calculi composed primarily of a drug and its metabolites. Understanding of drug metabolism and pharmacokinetics, particularly related to effects of urine pH on drug solubility and excretion, provides a rational basis for both prevention and treatment recommendations. When possible, clinicians should avoid or exercise great caution when prescribing these medications to patients with a prior history of stones. The second group of drug-induced calculi includes drugs that cause stones due to their metabolic effects, primarily on calcium or purine metabolism. Because these calculi are identical in physical composition to the more common nephrolithiasis types, careful medication history and high clinical suspicion are required for diagnosis of these drug-induced ''metabolic'' calculi. Most drugs in this class are readily expected based on their effects on urinary calcium excretion such as calcium/Vitamin D supplements and loop diuretics. Carbonic anhydrase inhibitors, including the antiepileptics topiramate and zonisamide, are also included in this group. Ammonium acid urate stones are endemic in developing countries due to dietary limitations and recurrent diarrheal illness, but rarely occur in developed countries. Identification of these stones should raise clinical suspicion of epidemiologic risk factors including recurrent urinary tract infections with urea-splitting organisms, inflammatory bowel disease, and laxative abuse. Interestingly, these unusual clinical scenarios can recapitulate a common biochemical pathway to stone formation. Protein matrix stones are another unusual stone type associated with specific epidemiologic factors, namely recurrent urinary infections and proteinuric end-stage renal disease. Although distinctly rare, protein matrix stones ...

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Urinary-Tract Stones Resulting from the Excretion of Oxypurinol

Cited by 48 publications

References 7 publications

Tumour Lysis Syndrome: Implications for Cancer Therapy

Tumour Lysis Syndrome: Implications for Cancer Therapy

Management of Hyperuricemia and Gout

Miscellaneous Stone Types

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