Summary
Twenty patients with epithelian ovarian cancer treated with DDP (cis-diammine-dichloroplatinum II) 50 mg/m2 were followed for 24 weeks in order to assess the nephrotoxicity of the drug. Ten patients received the total dose in one day with heavy osmotic hydration (Group A), and for the other 10 the dose was subdivided over 3 consecutive days (Group B). The renal tubular toxicity of DDP treatment was evaluated over a total of 120 courses. After the first DDP administration, there was a prompt, reversable and dose-dependent increase in the urinary excretion of β 2 microglobulin with no difference between the two groups: Group A from 405 to 990 and Group B from 109 to 585 ng/mg creatinine. An increase always occurred during subsequent courses, but it was significantly lower in Group B after the sixth course, from 125 to 331 ng/mg creatinine. A similar pattern was found for the urinary excretion of N-acetyl-glucosaminidase (NAG), a lysosomal enzyme of tubular origin. The percentage fraction of urinary sodium excretion (FeNa%) increased after each dose of DDP; Group A from 0.82 to 2.30 and Group B from 0.68 to 2.53. This effect was reversible and it occurred to the same extent during the subsequent courses. There was no impairment of the glomerular filtration rate. Thus, enzymuria and β 2 microglobulin excretion are a sensitive tool to reveal minor tubular damage. Their use to predict serious renal dysfunction in longitudinal studies, however, seems questionable.
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Harrap K, Jones M, Ray Wilkinson C et al. (1980) In: Prestayko AW et al. (eds) Cisplatin. Academic Press, New York, pp 193–212
Gonzales-Vitale JC, Hayes DM, Cvitkovic E, Sternberg S (1977) Renal pathology in clinical trials of cis-platinum (II) diamminedichloride. Cancer 39: 1362–1371
Hall DJ, Diasio R, Goplerud DR (1981) Cis-platinum in gynecologic cancer. III Toxicity. Am J Obstet Gynecol 141: 309–312
Blachley JD, Hill JB (1981) Renal and electrolyte disturbances associated with cisplatin. Ann Intern Med 95: 628–632
Comis RL (1980) In: Prestayko AW et al. (eds) Cisplatin. Academic Press New York pp 485–494
Hayes DM, Cvitkovic E, Golbey RB et al. (1977) High dose cis-platinum diamminedichloride. Amelioration of renal toxicity by mannitol diuresis. Cancer 39: 1372–1381
Vogl SE, Zaravinos T, Kaplan BH (1980) Toxicity of cisdiamminedichloroplatinum II given in a two-hour outpatient regimen of diuresis and hydration. Cancer 45: 11–15
Guarino AM, Miller DS, Arnold ST, Pritchard JB et al. (1979) Platinate toxicity: Past, present and prospects. Cancer Treat Rep 63: 1475–1483
Choie DD, Longnecker DS, Del Campo AA (1981) Acute and chronic cisplatin nephropathy in rats. Lab Invest 44: 397–402
Kovacs CJ, Braunschweiger PG, Schenken LL, Burholt DR (1982) Proliferative defects in renal and intestinal epithelium after cis-diamminedichloroplatinum (II). Br J Cancer 45: 286–294
Diener U, Knoll E, Langer B, Rautenstrauch H, Ratge D, Wisser H (1981) Urinary excretion of N-acetyl-β-D-glucosaminidase in patients receiving amikacin or cisplatinum. Clin Chim Acta 112: 149–157
Jones BR, Ravi B, Bhalla BS, Mladek J, Kaleya RN et al. (1980) Comparison of methods of evaluating nephrotoxicity of cis-platinum. Clin Pharmacol Ther 27: 557–562
Cohen AI, Harberg J, Citrin DL (1981) Measurement of urinary β 2 microglobulin in the detection of cisplatin nephrotoxicity. Cancer Treat Rep 65: 1083–1085
Kuhn JA, Argy WP, Rakowski TA et al. (1980) Nephrotoxicity of cis-diamminedichloroplatinum (II) as measured by urinary β-glucorinidase. Cancer Treat Rep 64: 1083–1086
Leaback H, Walker PG (1961) Studies on glucosaminidase: IV. The fluorimetric assay of N-acetyl-β-glucosaminidase. Biochem J 78: 151–156
Gilbert DN, Houghton DC, Bennet WM, Plamp CE, Reger K, Porter GA (1979) Reversibility of gentamicin nephrotoxicity in rat: Recovery during continous drug administration. Proc Soc Exp Biol Med 160: 99–103
Luft FC, Rankin LI, Sloan RS (1978) Recovery from Aminoglycoside nephrotoxicity with continued drug administration. Antimicrob Agents Chemother 3: 284–287
Evrin PE, Peterson PA, Wide L, Berggard J (1971) Radio-immunoassay of β 2 microglobulin in human biological fluids Scand J Clin Lab Invest 28: 439–444
Roger E, Kirk A (1968) Experimental design procedures for the behavioral sciences. Brooks/Cole Publishing Company, Belmont California
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Tirelli, A.S., Colombo, N., Cavanna, G. et al. Follow-up study of enzymuria and β 2 microglobulinuria during cis-platinum treatment. Eur J Clin Pharmacol 29, 313–318 (1985). https://doi.org/10.1007/BF00544087
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DOI: https://doi.org/10.1007/BF00544087