Abstract
Lysine is a major constituent of amino acid parenteral nutrition solutions which have recently been shown to increase the severity of various types of acute renal failure in the rat. In previous studies the authors have shown that high-dose lysine alone is capable of causing acute renal failure. However, it has remained unclear what the morphologic expression of this type of acute renal failure is in the maintenance phase of the syndrome, whether other amino acids produce a similar lesion, and whether lysine in lower doses also produces acute renal failure. In the present study the authors show that lysine, when given in a dose of 600 mg/rat over 4 hours, produced persisting acute renal failure which at 48 hours was characterized morphologically by a picture similar to that in human "acute tubular necrosis"--little overt tubular necrosis, but a focal loss of individual tubular cells with regenerative changes and mitotic figures. Extensive hyaline cast formation was seen, particularly in the thin limbs of the loops of Henle, and these thin limb casts were shown to contain Tamm-Horsfall protein. Equivalent doses of glycine, arginine, and glutamic acid and lower doses of lysine produced no significant renal morphologic or functional changes.
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- Abel R. M., Beck C. H., Jr, Abbott W. M., Ryan J. A., Jr, Barnett G. O., Fischer J. E. Improved survival from acute renal failure after treatment with intravenous essential L-amino acids and glucose. Results of a prospective, double-blind study. N Engl J Med. 1973 Apr 5;288(14):695–699. doi: 10.1056/NEJM197304052881401. [DOI] [PubMed] [Google Scholar]
- Arendshorst W. J., Finn W. F., Gottschalk C. W. Nephron stop-flow pressure response to obstruction for 24 hours in the rat kidney. J Clin Invest. 1974 May;53(5):1497–1500. doi: 10.1172/JCI107699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brezis M., Rosen S., Silva P., Epstein F. H. Selective vulnerability of the medullary thick ascending limb to anoxia in the isolated perfused rat kidney. J Clin Invest. 1984 Jan;73(1):182–190. doi: 10.1172/JCI111189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chan A. W., Burch H. B., Alvey T. R., Lowry O. H. A quantitative histochemical approach to renal transport. I. Aspartate and glutamate. Am J Physiol. 1975 Oct;229(4):1034–1044. doi: 10.1152/ajplegacy.1975.229.4.1034. [DOI] [PubMed] [Google Scholar]
- Finn W. F. Nephron heterogeneity in polyuric acute renal failure. J Lab Clin Med. 1981 Jul;98(1):21–29. [PubMed] [Google Scholar]
- Hoyer J. R., Seiler M. W. Pathophysiology of Tamm-Horsfall protein. Kidney Int. 1979 Sep;16(3):279–289. doi: 10.1038/ki.1979.130. [DOI] [PubMed] [Google Scholar]
- Malis C. D., Racusen L. C., Solez K., Whelton A. Nephrotoxicity of lysine and of a single dose of aminoglycoside in rats given lysine. J Lab Clin Med. 1984 May;103(5):660–676. [PubMed] [Google Scholar]
- Mason J., Torhorst J., Welsch J. Role of the medullary perfusion defect in the pathogenesis of ischemic renal failure. Kidney Int. 1984 Sep;26(3):283–293. doi: 10.1038/ki.1984.171. [DOI] [PubMed] [Google Scholar]
- Mogensen C. E., Sølling Studies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids. Scand J Clin Lab Invest. 1977 Oct;37(6):477–486. doi: 10.3109/00365517709101835. [DOI] [PubMed] [Google Scholar]
- Racusen L. C., Finn W. F., Whelton A., Solez K. Mechanisms of lysine-induced acute renal failure in rats. Kidney Int. 1985 Mar;27(3):517–522. doi: 10.1038/ki.1985.41. [DOI] [PubMed] [Google Scholar]
- Solez K., Heptinstall R. H. Intrarenal urinary extravasation with formation of venous polyps containing Tamm-Horsfall protein. J Urol. 1978 Feb;119(2):180–183. doi: 10.1016/s0022-5347(17)57428-5. [DOI] [PubMed] [Google Scholar]
- Solez K., Ideura T., Silvia C. B., Hamilton B., Saito H. Clonidine after renal ischemia to lessen acute renal failure and microvascular damage. Kidney Int. 1980 Sep;18(3):309–322. doi: 10.1038/ki.1980.141. [DOI] [PubMed] [Google Scholar]
- Solez K., Kramer E. C., Fox J. A., Heptinstall R. H. Medullary plasma flow and intravascular leukocyte accumulation in acute renal failure. Kidney Int. 1974 Jul;6(1):24–37. doi: 10.1038/ki.1974.74. [DOI] [PubMed] [Google Scholar]
- Toback F. G. Amino acid enhancement of renal regeneration after acute tubular necrosis. Kidney Int. 1977 Sep;12(3):193–198. doi: 10.1038/ki.1977.100. [DOI] [PubMed] [Google Scholar]
- Wedeen R. P., Thier S. O. Intrarenal distribution of nonmetabolized amino acids in vivo. Am J Physiol. 1971 Feb;220(2):507–512. doi: 10.1152/ajplegacy.1971.220.2.507. [DOI] [PubMed] [Google Scholar]
- Zager R. A., Johannes G., Tuttle S. E., Sharma H. M. Acute amino acid nephrotoxicity. J Lab Clin Med. 1983 Jan;101(1):130–140. [PubMed] [Google Scholar]
- Zager R. A., Venkatachalam M. A. Potentiation of ischemic renal injury by amino acid infusion. Kidney Int. 1983 Nov;24(5):620–625. doi: 10.1038/ki.1983.202. [DOI] [PubMed] [Google Scholar]