Summary
To detect whether the nephrotoxicity of cis-diaminodichloroplatinum (DDP) is acute and can be demonstrated at an early stage in man, a method for estimating the function of the kidneys during intensive hydration was devised. The method includes a calculation of the clearance of 125I-orthoiodohippurate and an estimation of the glomerular filtration rate (GFR) from fast changes of the extracellular volume (ECV) and the mean transit time of 99mTc-DTPA in this volume.
We examined nine patients with testicular cancer on 2 consecutive days for acute nephrotoxicity while they were undergoing treatment with cis-platinum. Placebo was given on day 1, cis-platinum on day 2. On both days the patients were hydrated with 4 l saline, glucose, and mannitol (0.5 l) over a period of 4 h, which resulted in an increase of 125I-orthoiodohippurate clearance on both days (P<0.01). The increase was, however, lower on the day of treatment with cis-platinum than on the day with placebo (P<0.05). There were no acute changes in the GFR. This indicates that treatment with DDP inhibits the active transport of 125I-orthoiodohippurate in the tubules; that is to say there is an acute effect on the kidney function.
There were no acute changes in the GFR, but in the long-term followup study we found that the GFR,had decreased significantly (P<0.05) after 2 months of treatment. During the first year after the initiation of treatment the GFR changes were found to progress. A significant increase in se-creatinine was not observed until 6 months after the initiation of treatment (P<0.05). The degree of chronic nephrotoxicity did not correlate in individual patients with the acute changes in kidney function.
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References
Bak Christensen A, Groth S, Nielsen H (1982) Optimal CdTe detector mounting for evaluation of the kidney function with 99mTc-DTPA. In: Raynaud C (ed) Nuclear medicine and biology, vol. 1. Perganon, Paris, pp 609–612
Chantler C, Garnett ES, Parsons V, Veall N (1969) Glomerular filtration rate measurement in man by the single injection method using 51Cr-EDTA. Clin Sci 37: 169–180
Cleare MJ (1977) Some aspects of platinum complex chemistry and their relation to antitumour activity. J Clin Haematol Oncol 7: 1–25
Cohen ML (1974) Radionuclide clearance techniques. Semin Nucl Med 4: 23–38
Einhorn JH, Danahue JP (1977) cis-Diamminedichloroplatinum, vinblastine and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med 87: 293–298
Frick GA, Ballentine R, Driever CW, Kramer WG (1979) Renal excretion kinetics of high-dose cis-dichlorodiammine-platinum(II) administered with hydration and mannitol diuresis. Cancer Treat Rep 63: 13–16
Gonzalez-Vitale JC, Hayes DM, Cvitkovic E, Sternberg SS (1977) The renal pathology in clinical trials of cis-platinum (II) diammine dichloride. Cancer 39: 1362–1371
Groth S, Aasted M (1981) 51Cr-EDTA clearance determined by one plasma sample. Clin Physiol 1: 417–425
Groth S, Bak Christensen A, Nielsen H (1983) CdTe detector registration of 99mTc-DTPA clearance. An assessment of kidney function without blood sampling. Eur J Nucl Med 8: 242–244
Hayes DM, Cvitkovic E, Golbey RB, Schreiner E, Hleson L, Krakoff IH (1977) High-dose cis-platinumdiamminedichloride: Amelioration of renal toxicity by mannitol diuresis. Cancer 39: 1372–1381
Ladegaard-Pedersen J (1972) Measurement of extracellular volume and renal clearance by a single injection of inulin. Scand J Clin Lab Invest 29: 145–153
Litterst CL, Le Roy AF, Guarino AM (1979) Disposition and distribution of platinum following parenteral administration of cis-Dichlorodiammineplatinum (ii) to animals. Cancer Treat Rep 63: 1485–1492
Madias NE, Harrington JT (1978) Platinum nephrotoxicity. Am J Med 65: 307–314
Matthews CME (1957) The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol 2: 36–53
Meijer S, Sleijfer DT, Mulder NH, Sluiter WJ, Marrink J, Koops HS, et al (1983) Some effects of combination chemotherapy with cis-platinum on renal function in patients with nonseminomatous testicular carcinoma. Cancer 51: 2035–2040
Prestayko AW, Bradner WT, Huftalen JB, et al (1979) Antileukemic (L1210) activity and toxicity of cis-dichlorodiammineplatinum(II) analogs. Cancer Treat Rep 63: 1503–1508
Pera MF, Harder HC (1978) Effects of furosemide (FM)- and mannitol (MN)-induced diuresis on the nephrotoxicity and physiologic disposition of cis-dichloro-diammineplatinum (CDDP) in rats. Proc AACR/ASCO 19: 100
Safirstein R, Miller P, Dikman S, Lyman N, Shapiro C (1981) Cisplatin nephrotoxicity in rats: defect in papilary hypertonicity. Am J Physil F175–F185
Schilsky RL, Anderson T (1979) Hypomagnesemia and renal mangesium wasting in patients receiving cisplatin. Ann Intern Med 90: 929–931
Sørensen PG, Nissen NH, Groth S, Rørth M (1985) Beta-2-microglobulin excretion: An indicator of long-term nephrotoxicity during cis-platinum treatment? Cancer Chemother Pharmacol 14: 247–249
Tauxe WN, Maher FT, Taylor WF (1971) Effective renal plasma flow. Estimation from theoretical volumes of distribution of intravenously injected 125I-orthoiodohippurate. Clin Proc 46: 524–531
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Groth, S., Nielsen, H., Sørensen, J.B. et al. Acute and long-term nephrotoxicity of cis-platinum in man. Cancer Chemother. Pharmacol. 17, 191–196 (1986). https://doi.org/10.1007/BF00306754
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DOI: https://doi.org/10.1007/BF00306754