Uroepithelial and nephrotubular toxicity in patients receiving ifosfamide/mesna: measurement of urinary N-acetyl-beta-D-glucosaminidase and beta-2-microglobulin.
The effect of three ifosfamide/mesna regimens on urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and beta-2-microglobulin (beta 2 M) was studied. All regimens produced significant increases in these urinary proteins, indicating nephrotubular damage. In regimen A (n = 15), plasma nitrobenzylpyridine (NBP) alkylating activity area under the curve (AUC) on day 1 correlated with the percentage increase above baseline of maximum urinary NAG activity (r2 = 0.538, P = 0.0022) and maximum beta 2 M concentration (r2 = 0.413, P = 0.0097). In regimen B (n = 5), plasma NBP alkylating activity AUC correlated with the percentage increase above baseline of maximum NAG activity (r2 = 0.843, P = 0.03) and beta 2 M (r2 = 0.78, P = 0.046). In these two regimens the renal exposure to ifosfamide metabolites correlated with the increases in urinary NAG and beta 2 M. The relation of these urinary protein abnormalities to longer term effects on renal function with different ifosfamide/mesna schedules requires further study.
Lewis
L D
LD
Division of Clinical Pharmacology, United Medical School, Guy's Hospital, London, U.K.
Burton
L C
LC
Harper
P G
PG
Rogers
H J
HJ
D000118:Acetylglucosaminidase / Q000652:urine*; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D015080:Mesna / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000652:urine; D001613:beta 2-Microglobulin / Q000652:urine*
D001613:beta 2-Microglobulin; D003404:Creatinine; D000118:Acetylglucosaminidase; D015080:Mesna; D007069:Ifosfamide