Atrial Natriuretic Factor Increases Glomerular Filtration Rate in the Experimental Acute Renal Failure Induced by Cisplatin
Cis-diamminodicloroplatinum (CP) is a recently developed antineoplastic agent that has a remarkably broad spectrum of clinical activity in the treatment of solid tumors (1). Use of this drug has significantly improved the response rate in patients treated for metastatic testicular and ovarian carcinomas. Additionaly,cisplatin is an important component of many treatment programs for the management of bladder carcinoma,squamous cell carcinoma of the head and neck,bronchogenic carcinoma of the lung,cervical and endometrial cancer.However the clinical use of the drug is largely hampered by its nephrotoxicity. In fact the degree of renal toxicity rather than the therapeutic response often determines the dosage of this therapeutic agent. A chronic,repetitive low dosage of cisplatin in rats also leads to kidney failure creating a situation similar to kidney insufficiency clinically observed during the prolonged chemotherapeutic regimens used for various malignancies (2). An acute single dose of CP induces in rats a non oligurie acute renal failure (ARF) that is characterized by a reduction of whole animal glomerular filtration rate (GFR),with increase in serum creatinine concentration,diminished urine osmolality, decreased U/P creatinine concentration ratios,and a significant increase in the fractional excretion of sodium (3). Development of cisplatin to its present level of clinical usefulness was greatly facilitated by studies in which hydration-diuresis maneuvers were used in dogs (4) and subsequently in humans (5). Another promising approach to limit CP nephrotoxicity is pharmacologic inhibition of cisplatin tubular secretion. Administration of drugs such as probenecid may be effective in decreasing the intracellular concentration of drug by inhibiting its uptake by the contraluminal cell membrane (6).
KeywordsGlomerular Filtration Rate Atrial Natriuretic Factor Bronchogenic Carcinoma Costant Infusion Single Nephron Glomerular Filtration Rate
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- 6.Ross D.A.,Gale G.R.: Reduction of renal toxicity of cis-dichlorodiammineplatinum (II) by probenecid. Cancer Treat. Rep. 63: 781–787 (1969)Google Scholar
- 7.Yuhas J.M. and Culo F.: Selective inhibition of the nephrotoxicity of cis-dichlorodiammineplatinum (II) by WR-2721 without altering anti-tumors properties. Cancer Treat. Rep. 64: 57–62 (1980)Google Scholar
- 8.McGinness J.E.,Proctor P.H.,Demopoulos H.B.: Amelioration of cis-platinum nephotoxicity by orgotein (superoxide dismutase). Physiol. Chem. and Physics 10: 267–273 (1978)Google Scholar
- 11.Camargo M.J.F.,Kleinert H.D.,Atlas S.A.,Sealey J.E.,LaraghJ.H.,Maack T.: Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. Am. J. Physiol. 246: F447 - F456 (1984)Google Scholar
- 12.Beasley D.,Malvin R.L.: Atrial extracts increase glomerular filtration rate in vivo. Am. J. Physiol. 248: F24 - F30 (1985)Google Scholar
- 13.Goormaghtigh H.: Vascular and circulatory changes in renal cortex in the anuric crush-syndrome. Proc. Soc. Expt. Biol. Med. 59: 303–305 (1945)Google Scholar
- 15.Farber J.L.: The role of calcium in cell death. Life Sci. 29: 12891295 (1981)Google Scholar