Urinary excretion of N-acetyl-beta-glucosaminidase (NAG) is an early marker of nephrotoxicity. NAG activity was assayed by the fluorimetric method of Leaback and Walker in 17 patients treated (22 courses) with carboplatin (CBDCA, 220–550 mg/m2) before infusion and 24, 48, 72 and 96 h after. Increased excretion of NAG, a sensitive index of renal tubular damage, was observed following 10 of the 22 courses. A transient increase in plasma creatinine and/or abnormal proteinuria was observed in 6 cases. Impaired renal function prior to therapv seems to be a predisposing factor to the nephrotoxicity.
Get full access to this article
View all access options for this article.
References
1.
CalvertA.H., HarlandS.J., NewellD.R., SiddikZ.H., HarrapK.R.: Phase I study with carboplatin at the Royal Marsden Hospital.Cancer Treat. Rev., 12(Suppl. A): 51–57, 1985.
2.
CanettaR., RozencweigM., CarterS.K.: Carboplatin: the clinical spectrum to date.Cancer Treat. Rev., 12(Suppl. A): 125–136, 1985.
3.
CurtG.A., GrygieiJ.J., CordenB.J., OzolsR.F., WeissR.B., TellD.T., MyersC.E., CollinsJ.M.: A phase I and pharmacokinetic study of diammine-cyclobutane-dicarboxylatoplatinum (NSC 241240).Cancer Res., 43: 4470–4473, 1983.
4.
DienerV., KnollE., LangerB.: Urinary excretion of N-acetyl-beta-D-glucosaminidase and alanine-aminopeptidase in patients receiving amikacin or cis-platinum.Clin. Chim. Acta, 112: 149–157, 1891.
5.
Editorial: Cisplatin.Lancet, 1: 374–375, 1982.
6.
HarrapK.R., JonesM., WilkinsonC.R., McClinkH., SparrowS., MitchleyB.C.V., ClarkeS., VeaseyA.: Antitumor toxic and biochemical properties of cisplatin and eight other platinum complexes: In: Cisplatin-Current Status and New Developemnts.PrestaykoA.W., CrookeS.T., CarterS.K. (eds.), pp. 193–212, Academic Press, New York, 1980.
7.
HartandS.J., NewellD.R., SiddikZ.H., ChadwickR., CalvertA.H., HarrapK.R.: Pharmacokinetics of cis-diamine-1,1-cyclobutane dicarboxylate platinum (II) in patients wtih normal and impaired renal function.Cancer Res., 44: 1693–1697, 1984.
8.
HayesD.M., CvitkvicE., GolbeyR.B., ScheinerE., HelsonH., KrakoffI.H.: High dose cis-platinum diamine dichloride: amelioration of renal toxicity by mannitol diuresis.Cancer, 39: 1372–1381, 1977.
9.
HelinH., PasternakA., HakalaT., PeuttinenK., KagerO.: Glomerular electron-dense deposits and circulating immunocomplexes in patients with malignant tumours.Clin. Nephrol., 14: 23–28, 1980.
10.
JonesB.R., BhallaR.B., MladekJ., KaleyaR.N., GrallaR.J., AlcockN.W., SchartzM.K., YoungC.W., ReidenbergM.M.: Comparison of methods of evaluating nephrotoxicity of cisplatinum.Clin. Pharmacol. Ther., 27: 557–562, 1980.
11.
KoellerJ.M., TrumpD.L., TutschK.D., EarhartR.H., DavisT.E., TormeyD.C.: Phase I clinical trial and pharmacokinetics of carboplatin (NSC 241240) by single monthly 30-minute infusion.Cancer, 57: 222–225, 1986.
12.
KunimC.H., ChesneyR.M., CraigW.A., EnglandA.C., De AngelisC.: Enzymuria as marker of renal injury and disease: studies of N-acetyl-beta-glucosaminidase in the general population and in patients with renal disease.Pediatrics, 62: 751–760, 1978.
13.
LeabackB.H., WalkerP.G.: Studies on glucosaminidase. The fluorimetric assay of N-acetyl-beta-glucosaminidase.Biochem. J., 78: 151–156, 1961.
14.
LeeF.H., CanettaR., IsselB.F., LenazL.: New platinum complexes in clinical trials.Cancer Treat. Rev., 10: 39–51, 1983.
15.
OstrowS., EgorinM.J., HahnD., MarkusS., AisnerJ., ChandP., Le RoyA., BachurN.R., WiernikP.H.: High-dose cosplatin therapy using mannitol versus furosemide diuresis: comparative pharmacokinetics and toxicity.Cancer Treat. Rep., 65: 73–81, 1981.
PriceR.G.: Urinary N-acetyl-beta-D-glucosaminidase (NAG) as an indicator of renal disease.Curr. Probl. Clin. Biochem., 9: 150–163, 1979.
18.
RoseW.C., SchuringJ.E.: Preclinical antitumoral and toxicologic profile of carboplatin.Cancer Treat. Rev., 12(Suppl. A): 1–19, 1985.
19.
ViganòA., CavannaG., CapodoglioB., AssaelB.L., SalmonaM.: Methodological and clinical aspects of urinary N-acetyl-beta-glucosaminidase in pediatric subjects.Biochem. Med., 25: 26–33, 1981.
20.
VoglS.E., ZaravinosT., KaplanB.H.: Toxicity of cis-diamminedichloroplatinum II given in a two-hour outpatient regimen of diuresis and hydration.Cancer, 45: 11–15, 1980.
21.
Von HoffD.D., SchilskyR., ReichertC.H., Red-dickR.L., RozencweigM., YoungR.C., MuggiaF.M.: Toxic effects of cis-dichlorodiammineplatinum (II) in man.Cancer Treat. Rep., 63: 1527–1531, 1979.
