Purine excretion during tumor lysis in children with acute lymphocytic leukemia receiving allopurinol: relationship to acute renal failure.
We measured serial urine levels of hypoxanthine, xanthine, and uric acid in 19 children with acute lymphocytic leukemia (ALL) receiving allopurinol therapy during tumor lysis; four of these children developed acute renal failure. The urinary excretion of uric acid rose moderately from 447 +/- 251 micrograms/dl glomerular filtrate before chemotherapy to 778 +/- 463 micrograms/dl glomerular filtrate during tumor lysis (P less than 0.05) whereas the urinary excretion of hypoxanthine (17.9 +/- 15 to 292 +/- 213 micrograms/dl glomerular filtrate) and xanthine (74 +/- 62 to 1091 +/- 1085 micrograms/dl glomerular filtrate) rose dramatically (P less than 0.001). The urinary excretion of uric acid, hypoxanthine, and xanthine per deciliter of filtrate was significantly higher (P less than 0.001) in those who developed acute renal failure than in those who did not, but the highest urine concentration of these purine metabolites did not differ in the two groups. In all 19 children, the highest urine concentration of uric acid and hypoxanthine during tumor lysis did not exceed the solubility limit of each in an alkaline urine specimen. In contrast, the peak urine concentration of xanthine exceeded its solubility limit in an alkaline urine specimen in 16 of 19 children. The urine sediment during the period of tumor lysis was examined by diffuse reflectance infrared spectroscopy; precipitated xanthine was found in sediment from eight of the 19 children, was significantly (P less than 0.001) associated with a urine xanthine level greater than 350 mg/dL, and occurred with equal frequency in those who did or did not develop acute renal failure. We conclude that urinary excretion of hypoxanthine and xanthine increases dramatically whereas uric acid excretion rises moderately in children undergoing tumor lysis while receiving allopurinol, that acute renal failure occurs in children with a higher purine load per deciliter of glomerular filtrate, but that factors other than tubular precipitation of purine metabolites are likely to be involved in the pathogenesis of renal failure during tumor lysis.
Andreoli
S P
SP
Clark
J H
JH
McGuire
W A
WA
Bergstein
J M
JM
D058186:Acute Kidney Injury / Q000209:etiology / Q000652:urine*; D000493:Allopurinol / Q000627:therapeutic use*; D002648:Child; D005919:Glomerular Filtration Rate; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000652:urine*; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000652:urine; D013055:Spectrophotometry, Infrared; D014527:Uric Acid / Q000652:urine*; D019820:Xanthine; D014970:Xanthines / Q000652:urine*
D007042:Hypoxanthines; D014970:Xanthines; D019820:Xanthine; D014527:Uric Acid; D019271:Hypoxanthine; D000493:Allopurinol