Summary
The usefulness of pretreatment biochemical parameters in the prediction of nephrotoxicity associated with cisplatin treatment was studied. Twenty-two patients, who received 29 cycles of cisplatin, were evaluated. Cisplatin was given every 3–4 weeks with saline and mannitol. Azotemia occurred in almost all patients and was transient, peaking 1–2 weeks after therapy. The change in serum creatinine from baseline to peak correlated inversely with pretreatment serum albumin (r=-0.73; P<0.01) and with pretreatment uric acid (r=0.76; P<0.01). Ten patients with uric acid level of <6 mg/dl were receiving allopurinol. The competition between organic anions and cisplatin for excretion may, in part, explain the protective effects of hypouricemia. Hypoalbuminemia affects peritubular oncotic pressure and may in turn affect platinum excretion. Hypoalbuminemia also reduces the half-life of cisplatin, exposing the kidney to more of the unbound filterable drug.
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References
Blachley JD, Hill JB (1981) Renal and electrolyte disturbances associated with cisplatin. Ann Intern Med 95: 628–632
Borsch RF, Pleasants ME (1979) Inhibition of cis-platinum nephrotoxicity by diethyldiothiocarbamate rescue in a rat model. Proc Natl Acad Sci USA 76: 6611–6616
Brenner BM, Troy JL (1971) Postglomerular vascular protein concentration. Evidence for a casual role in governing fluid reabsorption and glomerular balance by the proximal tubule. J Clin Invest 50: 336–341
Campbell B, Kalman S, Jacobs C (1981) Cisplatinum nephrotoxicity relationship to serum levels and pre-treatment creatinine. Proc Am Assoc Cancer Res Am Soc Clin Oncol 22: 354–356
Chary KK, Higby DJ, Henderson ES (1977) Phase I study of high dose cis-dichlordiammine platinum (II) with forced diuresis. Cancer Treat Rep 61: 362–372
Einhorn LH, Donohue J (1977) cis-Dichlorodiammineplatinum, vinblastine and bleomycin combination therapy in disseminated testicular cancer. Ann Intern Med 87: 293–298
Goldberg ID, Garnick MB, Bloomer WD (1984) Urinary tract toxic effects of cancer therapy. J Urol 132: 1–6
Gullo JJ, Litterst CL, Maguire PJ (1980) Pharmacokinetics and protein binding of cis-dichloroplatinum (II) administered as a 1-hour or as a 24-hour infusion. Cancer Chemother Pharmacol 5: 21–26
Hayes D, Cvitkovic E, Golbey R (1977) Amelioration of renal toxicity of high dose cis-platinum by manitol-induced diuresis. Cancer 39: 1372–1381
Holmes EW, Kelley WN, Wyngaarden JB (1972) The kidney and uric acid secretion in man. Kidney Int 2: 115–121
Howel SB, Taette R (1980) Effects of sodium thiosulfate on cis-dichlorodiammine platinum (II) toxicity and antitumour activity in L1210 leukemia. Cancer Treat, Rep 64: 611–616
Madias NE, Harrington JT (1978) Platinum nephrotoxicity. Am J Med 65: 307–314
Prestayko AW, Crooke ST, Carter SK (1980) Cisplatin — Current status and new developments. Academic, New York
Ross DA, Gayle GR (1979) Reduction of renal toxicity of cis-dichlorodiammineplatinum (II) by probenicid. Cancer Treat Rep 63: 781–787
Stark JJ, Howel SB (1978) Nephrotoxicity of cisplatinum (II) dichlorodiammine. Clin Pharmacol Ther 23: 461–466
Stewart DJ, Benjamin RS, Zimmerman S (1983) Clinical pharmacology of intra-arterial cisdiammine-dichloroplatinum. Cancer Res 43: 917–920
Weiner WM, Jacobs C (1983) Mechanisms of cisplatin nephrotoxicity. Fed Proc 42: 2974–2978
Young RC, Von Hoff DD, Gormley P (1979) cis-dichlorodi-ammuneplatinum (II) for the treatment of advanced ovarian cancer. Cancer Treat Rep 63: 1539–1553
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Nanji, A.A., Stewart, D.J. & Mikhael, N.Z. Hyperuricemia and hypoalbuminemia predispose to cisplatin-induced nephrotoxicity. Cancer Chemother. Pharmacol. 17, 274–276 (1986). https://doi.org/10.1007/BF00256698
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DOI: https://doi.org/10.1007/BF00256698