Nephrotoxicity pp 147-170 | Cite as

Drug Induced Renal Effects of Cyclosporine, Aminoglycoside Antibiotics and Lithium: Extrapolation of Animal Data to Man

  • George A. Porter
  • William M. Bennett


Drugs may have either a beneficial or adverse effect on renal function. It is the latter effect we wish to focus on since 10% nephrological consultations involve the possibility of drug-induced renal injury (Porter and Bennett, 1985). Thus information regarding prevalence, clinical presentation, pathophysiological mechanisms of injury and methods of modifying it have become a significant area of research. Most studies are designed to assess the potential risk which a drug possesses for inducing significant nephrotoxicity in a given patient. Since toxicology studies the adverse effects of chemicals on living organisms and assesses the probability of their occurrence, the two expected outcomes of a toxicological analysis are risk assessment and risk prediction. However, clinical toxicology combines the science of toxicology with the art of medicine; thus, the contribution of each is critical in the study of druginduced nephrotoxicity. Scientifically, both the quantitative and qualitative in vivo and in vitro effect of drugs in the kidney are important contributors to the final assessment. However, the answer most often sought i.e., to predict occurrence in man, must occur in the face of limited scientific data as it involves the extrapolation of one set of exposure conditions to another circumstance involving different species.


Lithium Treatment Aminoglycoside Antibiotic Nephrogenic Diabetes Insipidus Lithium Therapy Myeloid Body 


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  1. Adelman, R.D., Spangler, W.L., Beasom, F., Ishizake, G., and Conzelman, G.M., 1979, Furosemide enhancement of experimental gentamicin nephrotoxicity: comparison of functional and morphological changes with activities of urinary enzymes, J. Infect. Dis., 140 :342.PubMedCrossRefGoogle Scholar
  2. Angrest, B.M., Gershon, S., Levitan, S.J., and Blumberg, A.G., 1970, Lithium-induced diabetes insipidus-like syndrome, Compr. Psychiat., 11:141.CrossRefGoogle Scholar
  3. Appel, G.B., and Neu, H.C., 1978, Gentamicin in 1978, Am. Intern. Med., 89:528.CrossRefGoogle Scholar
  4. Appel, G.B., Siegel, N.J., Appel, A.S., and Hayslett, J.P., 1981 Studies on the mechanism of non-oliguric experimental acute renal failure, Yale J. Biol. Med., 54:273.PubMedGoogle Scholar
  5. Arruda, J.A., Dytko, G., Mola, R., and Kurtzman, N.A., 1980, On the mechanism of lithium-induced renal tubular acidosis : studies in the turtle bladder, Kidney Int., 17:196.PubMedCrossRefGoogle Scholar
  6. Ayd, F.J., 1978, Lithium-induced kidney damage: an update, Internet. Drug Thera. Newsletter, 13:17.Google Scholar
  7. Bantle, J.P., Nath, K. A. , Sutherland, D.E., Najarian, J. S. , Ferris, T. F. , 1985, Effects of cyclosporin on the renin angiotensin aldosterone system and potassium excretion in renal transplant patients, Arch. Int. Med., 145:505.CrossRefGoogle Scholar
  8. Batlle, D.C., von Riotte, A., Gaviria, M., and Grupp, M., 1985, Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy, N. Eng. J. Med., 312:408.CrossRefGoogle Scholar
  9. Bauer, L.A. and Bloum, B.A., 1982, Gentamicin pharmacokinetics : Effect of aging in patients with normal renal function, J. Am. Geriatr. Soc., 30 :309.PubMedGoogle Scholar
  10. Bendz, H., 1983, Kidney functions in lithium-treated patients : a literature survey, Acta Psychiat. Scand., 68:303.PubMedCrossRefGoogle Scholar
  11. Bendz, H., Andersch, S., and Aurell, M., 1983, Kidney function in an unselected lithium population, A cross-sectional study, Acta Psychiat. Scand., 68:325.PubMedCrossRefGoogle Scholar
  12. Bennett, W.M., 1985, Basic mechanisms and pathophysiology of cyclosporine nephrotoxicity, Transpl. Proc., 17:297.Google Scholar
  13. Bennett, W.M. and Norman, D.J., 1986, Action and toxicity of cyclosporine, Ann. Rev. Med., 37:215.PubMedCrossRefGoogle Scholar
  14. Bennett, W.M., Pulliam, J.P., 1983, Cyclosporine nephrotoxicity, Ann. Intern. Med., 99:851.PubMedCrossRefGoogle Scholar
  15. Bennett, W.M., Wood, C.A., Houghton, D.C., and Gilbert, D.N., 1986, Modification of experimental aminoglycoside nephrotoxicity, Am. J. Kidney Dis., 8:292.PubMedGoogle Scholar
  16. Bennett, W.M., Gilbert, D.N., Houghton, D., and Porter, G.A., Gentamicin nephrotoxicity in man: morphologic and pharmacological features, West. J. Med., 126:65.Google Scholar
  17. Bennett, W.M., Hartnett, M.N., Gilbert, D.N., Houghton, D.C. and Porter, G.A., 1979, Effect of sodium intake on gentamicin nephrotoxicity in the rat, Proc. Soc. Biol. Med., 151:736.Google Scholar
  18. Bennett, W.M., Elliott, W.C., Houghton, D.C., Gilbert, D.N., DeFehr, J. and McCarron, D.A., 1982, Reduction of experimental gentamicin nephrotoxicity in the rat by dietary calcium loading, Antimirob. Agent Chemother., 22:508.CrossRefGoogle Scholar
  19. Bentley, P.J. and Wasserman, A., 1972, The effects of lithium in the permeability of an epithelial membrane, the toad urinary bladder, Biochim. Biophys. Acta, 266:285.PubMedCrossRefGoogle Scholar
  20. Bergeron, M.G., Lessard, C., Ronald, A., Stiver, G., Van Rooyer, C. E. , and Chadwick, P., 1983, Three to eight weeks of therapy with netilmicin: toxicity in normal and diabetic patients, J. Antimicrob. Chemothera., 12:245.CrossRefGoogle Scholar
  21. Buss, W., Bennett, W.M., 1987, Cyclosporine in vivo produces a dose dependent inhibition of protein synthesis, Fed. Proc., 46:555.Google Scholar
  22. Cade, J.F.J., 1949, Lithium salts in the treatment of psychotic excitement, Med. J. Aust., 36:349.Google Scholar
  23. Canadian Multicenter Transplant Study Group., 1983, A randomized clinical trial of cyclosporine in cadaveric renal transplantation, New Encg. J. Med., 309:809.CrossRefGoogle Scholar
  24. Canafax, D.M., Torres, A., Fryd, D.S., Heil, J.E., Strand, M.H., Ascher, N.L., Payne, W.D., Sutherland, D., Simmons, R., Najarian, J.S., 1986, The effects of delayed function on recipients of cadaver renal allografts, Transplantation, 41:177.PubMedCrossRefGoogle Scholar
  25. Carney, S.L., Wong, L.M., and Dirks, J.H., 1980, Effects of lithium treatment on rat tubule function, Nephron, 25:293.CrossRefGoogle Scholar
  26. Chen, P. J. S. , Miller, G. J. , Long, J.F. and Waity, J. A. , 1979, Renal uptake and nephrotoxicity of aminoglycosides during urinary alkalinization in the rat, Clin. Exp. Pharmacol. Physiol., 6:317CrossRefGoogle Scholar
  27. Christensen, S., Hansen, B.B., and Faarup, P., 1982, Functional and structural changes in the rat kidney by long-term lithium treatment, Renal Physiol., 5:95.PubMedGoogle Scholar
  28. Christensen, S., Kristensen, A.R., and Faarup, P., 1981, Effects of lithium and neuroleptics and combinations of the two on renal function and structure in rats, Acta Pharmacol. Toxicol., 49:161.CrossRefGoogle Scholar
  29. Christensen, S., Kusano, E., Yusufi, A. N. K. , Murayama, N. and Dousaa, T.P., 1985, Pathogenesis of nephrogenic diabetes insipidus due to chronic abnormalities of lithium in rats. J. Clin. Invest., 75:1869.PubMedCrossRefGoogle Scholar
  30. Cleaveland, S.A., 1913, A case of poisoning by lithium, JAMA, 60, 722.CrossRefGoogle Scholar
  31. Cojocel, C., and Hook, J.B., 1983, Effects of acute exposure to gentamicin on renal handling of proteins, Toxicology, 28:347.PubMedCrossRefGoogle Scholar
  32. Coopen, A., Bishop, M.E., Bailey, J.E., Cattell, W., and Price, R.G., 1980, Renal function in lithium and non-lithium treated patients with affective disorders, Acta Psychiat. Scand., 62:343.CrossRefGoogle Scholar
  33. Cronin, R.E., Nix, K.L., Ferguson, E.R., Southern, P.M., and Henrick, W.L., 1982, Renal on composition and Na-K-ATPase activity in gentamicin nephrotoxicity, Am. J. Physiol., 242:F477.Google Scholar
  34. Curtis, J.J., Luke, R.G., Jones, P., Dubovsky, E.V., Whelchel, J.D., Diethelm, A.G., 1986, Cyclosporine in therapeutic doses increases renal allograft resistance, Lancet, 2:477.PubMedCrossRefGoogle Scholar
  35. DeBroe, M. E. , Paulus, G. J. , Verpooten, G.A., Roels, F., Buyssens, N., Wedeen, R., Van Hooj, F. and Tulkens, P.M.,1984, Early effects of gentamicin, tobramycin and amikacin on the human kidney. Kidney Int., 25:643.PubMedCrossRefGoogle Scholar
  36. Donker, A.J.M., Prince, E., Meijer, S., Sluiter, W.J., Van Berkestin, J.W.B.M., Dois, L.C.W., 1979, A renal function study in 30 patients on long-term lithium therapy, Clin. Nephrol., 12:254.PubMedGoogle Scholar
  37. Eknoyan, G., Gentry, L., and Bulger, R., 1984, Attenuation of gentamicin induced acute renal failure by phosphate depletion, Kidney Int. 25:229.Google Scholar
  38. Eliahou, H., Iaina, A. and Serban, I., 1984, Verapamils’ beneficial effect and cycle nucleotides in gentamicin-induced acute renal failure, Nephron., 4:323A.Google Scholar
  39. Elliott, W.C., Houghton, D.C., Gilbert, D.N., DeFehr, J., and Bennett, W.M., 1982 Gentamicin nephrotoxicity. I Degree and permanence of acquired insensitivity, J. Lab. Clin. Med., 100:501.PubMedGoogle Scholar
  40. Ellis, G.G., Coppen, A., and Glen, A.I.M., 1971, Urine concentration in depressive illness, J. Neurol. Neurosurg. Psychiat., 34:30.PubMedCrossRefGoogle Scholar
  41. Elzinga, L. , Kelley, V., Houghton, D.C., Bennett, W.M., 1987, Fish oil modifies experimental cyclosporine nephrotoxicity and decreases renal prostaglandins, Transplantation, 43:271.PubMedCrossRefGoogle Scholar
  42. English, J., Evan, A., Houghton, D.C., Bennett, W.M., 1987, Cyclosporine induced acute renal dysfunction in the rat: evidence for arteriolar vasoconstriction with preservation of tubular function, Transplantation (in press) .Google Scholar
  43. English, J., Gilbert, D.N., Kohlhepp, S.J., Kohner, P.W., Mayor, G. , Houghton, D.C. and Bennett, W.M., 1985, Alternatives of experimental tobramycin nephrotoxicity with ticarcillin, Antimicrob. Agent Chemothera., 27 :897.CrossRefGoogle Scholar
  44. Evans, A.P. and 011erich, D.A. , 1972, The effect of lithium carbonate on the structure of the rat kidney, Am. J. Anat., 134:97.CrossRefGoogle Scholar
  45. Finn, W.F., 1987, Renal vascular effects of cyclosporine, Transpl. Immunol. Letter, 3:4.Google Scholar
  46. Forrest, J.N., Jr., Cohen, A.D., Torretti, J., Himmelhock, J.M., and Epstein, F.H., 1974, On the mechanism of lithium-induced diabetes insipidus in man and the rat, J. Clin. Invest., 53:1115.PubMedCrossRefGoogle Scholar
  47. Gibbons, C. P. , Wiley, K. N. , Lindsey, N.J., Fox, M., Beck, S., Slater, D.N., Preston, F. E. , Brown, C. B. , Raftery, A. T. , Cortical and vascular prostaglandin synthesis during renal allograft rejection in the rat, Transplantation, 43:472Google Scholar
  48. Gibey, R., Dupond, J.L., Alber, D., Leconte d’Fleus, R., and Henry, J. C. , 1981, Predictive value of urinary N-acetyl-beta-D-glucosaminidase (NAG), Alanine-aminopeptidase (AAP) and beta-2-microglobulin (B2M) in evaluating nephrotoxicity of Gentamicin, Clin. Chem. Acta, 116:27.CrossRefGoogle Scholar
  49. Giuliano, R. A. , Verpooten, G.A., Verbist, L., Wedeen R.P., DeBroe, M. E. , 1986, In vivo uptake kinetics of aminoglycosides in the kidney cortex of the rat. J. Pharmacol. Explt. Therap., 236:470.Google Scholar
  50. Gold, B.W., Robertson, G.L., Post, R.M., Kaye, W., Ballenger, J., Rubinow, D., and Goodwin, F.K., 1983, The effects of lithium on osmoregulation of arginine vasopressin sections J. Clin. Endocrin. Metabolism, 56:295.CrossRefGoogle Scholar
  51. Grof, P., Hux, M., Pressler, B., and O’Sullivan, K., Kidney Function and response to lithium treatment, Prog. Neuropsychopharmacol. Biol. Psychiat., 6:491.Google Scholar
  52. Hall, B.M., Tiller, D.J., Duggin, G.G., Horvath, J.S., Farnsworth, A., May, J., Johnson, J.R., Shiel, A.G., 1985, Post-transplant acute renal failure in cadaver renal recipients treated with cyclosporine. Kidney Int., 28:178.PubMedCrossRefGoogle Scholar
  53. Hansen, H.E., Mogensen, C.E., Sorensen, J.L., Norgaard, K., Heilskov, J., and Anderesen, A., 1981. Albumin and beta-2-microglobulin excretion in patients on long-term lithium treatment, Nephron, 29:229.PubMedCrossRefGoogle Scholar
  54. Harris, C.A. and Jenner, F.A., 1972, Some aspects of the inhibition of the action of antidiuretic hormone by lithium ion in rat kidney and bladder of toad Bufo Marinos, Br. J. Pharmacol., 44:223.PubMedCrossRefGoogle Scholar
  55. Hecht, B., Kashgarian, M., Forrest, J.N. Jr., and Hayslett, J.P., 1978, Micropuncture study on the effect of lithium on proximal and distal tubule function in the rat kidney, Pfleugers Arch., 377:69.CrossRefGoogle Scholar
  56. Heinert, G., Wyrobrik, J., Scherberick, J., Mondorf, W. and Weber, M., 1982, Quantitative histophotometry analyzing significant inductive and alternative features of aminoglycoside application upon kidney tubule proteins, Urol. Int., 37:221.PubMedCrossRefGoogle Scholar
  57. Hestbech, J., Hansen, H.E., Amdisen, A., and Olsen, S., 1977, Chronic renal lesions following long-term treatment with lithium, Kidney Int., 12:205.PubMedCrossRefGoogle Scholar
  58. Houghton, D.C., Hartnett, M.N., Campbell-Boswell, M., Porter, G.A., and Bennett, W.M., 1976, A light and electron microscopic analysis of gentamicin nephrotoxicity in the rat, Am. J. Pathol., 82:589.PubMedGoogle Scholar
  59. Houghton, D.C., P lamp, C.E., DeFehr, J.M., Bennett, W.M., Porter, G.A., and Gilbert, D.N., 1978, Gentamicin and tobramycin nephrotoxicity: a morphologic and functioned comparison in the rat, Am. J. Pathol., 93:137.PubMedGoogle Scholar
  60. Hullin, R.P., Culey, V.P., Birch, N.J., 1979, Renal function after longterm treatment with lithium, Br. Med. J., 1:1457.PubMedCrossRefGoogle Scholar
  61. Humes, H.D., 1987, Renal tubulointerstitial effects of cyclosporine, Transpl. Immunol. Letter, 3:6.Google Scholar
  62. Jacobsen, N.O., Olesen, O.V., Thomsen, K., Ottosen, P.D., and Olsen, S., 1982, Early changes in renal distal convoluted tubules and collecting ducts of lithium-treated rats: light microscopy, enzyme histodensity and H-thymidine autoradiography, Lab. Invest., 46:298.PubMedGoogle Scholar
  63. Jenner, F.A. and MacNell, S., 1975, The effect of lithium ions on the antidiuretic action of vasopressin in the rat, Br. J. Pharmacol., 55:527.PubMedCrossRefGoogle Scholar
  64. Jensen, S.B. and Rickers, H., 1984, Glomerular filtration rate during lithium therapy, A longitudinal study, Acta Psychiat. Scand., 70:235.PubMedCrossRefGoogle Scholar
  65. Johnson, G. F. S. , Hunt, G. E. , Duggin, G.G., Harrath, J.S. and Tiller, D. J. , 1984, Renal functions and lithium treatment: Initial and follow-up tests in manic depressive illness. J. Affect. Disord. 6:249.PubMedCrossRefGoogle Scholar
  66. Jorgensen, F., Larsen, S., Spanager, B., Clausen, E., Tango, M., Brinch, E., and Brun, C., 1984, Kidney function and quantitative histological changes in patients on long-term lithium therapy, Acta Psychiat. Scand., 70:455.PubMedCrossRefGoogle Scholar
  67. Kahan, B.D., Van Buren, C. T. , Lin, S. N. , Ono, Y., Agostino, G., Lagrue, S.J., Boileau, M.,Payne, W.D., Kerman, R.H., 1982, Immunopharmacological monitoring of cyclosporin A treated recipients of cadaveric kidney allografts, Transplantation, 34:36.PubMedCrossRefGoogle Scholar
  68. Kaloyanides, G.G., Pastoriza-Munoz, E., 1980, Aminoglycoside nephrotoxicity, Kidney Int., 18:571.PubMedCrossRefGoogle Scholar
  69. Kawaguchi, A., Goldman, M.H., Shapiro, R., Foegh, M.L., Ramwell, P.W., Lower, R.R., 1985, Increase in urinary thromboxane B2 in rats caused by cyclosporine, Transplantation, 40:214.PubMedCrossRefGoogle Scholar
  70. Kling, M.A., Fox, J.G., Johnston, S.M., Tolkoff-Rubin, N.E., Rubin, R.H., and Colvin, R.B., 1984, Effects of long-term lithium administration on renal structure and function in rats. A destructive tubular lesion, Lab. Invest., 50:526.PubMedGoogle Scholar
  71. Klintmalm, G., Bohman, S. O. , Sundelin, B., Wilczek, H., 1985, Interstitial fibrosis in renal allografts after 12 to 46 months of cyclosporin treatment: beneficial effect of low doses in the early posttransplantation period, Lancet, 2:950.Google Scholar
  72. Kluwe, W.M., and Hook, J.B., 1978, Analysis of gentamicin uptake by the rat renal cortical tissue, Toxicol. Appl. Pharmacol., 45:531.PubMedCrossRefGoogle Scholar
  73. Laurent, G., Maldagne, P., Carlier, M.B., and Tulkens, P.E., 1983, Increased renal DNA synthesis in vivo after administration of low doses of gentamicin in the rat, Antimicro. Agent Chemothera., 24:586.CrossRefGoogle Scholar
  74. Lippmann, KS., 1982, Is lithium bad for the kidneys?, Clin. Psvchiat., 43:220.Google Scholar
  75. Lokkegaard, H., Andersen, N.F., Henrisken, E., Bartels, P.D., Brahm, M., Baastrup, P.C., Joorgensen, H.E., Larsen, M., Munck, O., Rosmusseu, K.,1985, Renal function in 153 manic-depressive patients treated with lithium for more than 5 years. Acta Psychiat. Scand. 71:347.PubMedCrossRefGoogle Scholar
  76. Luft, F.C., Patal, V., Yom, M.N., Patel, B. and Kleit, S.A., 1978, Experimental aminoglycoside nephrotoxicity. J. Lab. Clin. Med., 86:213.Google Scholar
  77. Luft, F.C., Patel, V., Yom, M.N., Patel, N., and Kliet, S.A., Nephrotoxicity of cephalosporin-gentamicin combinations in rats, Antimicrob. Agent Chemother., 4:831.Google Scholar
  78. Mannion, J.C., Block, R., and Popovich, N.G., 1981, Cephalosporinaminoglycoside synergistic nephrotoxicity: fact of fiction? Drug Intell. Clin. Pharm., 15:248.PubMedGoogle Scholar
  79. Martinez-Maldonado, M. and Opava-Stetzer, S., 1977, Distal nephron function in the rat during lithium chloride infusion, Kidney Int., 12:17.PubMedCrossRefGoogle Scholar
  80. Martinez-Maldonado, M., Stavroulaki-Tsapara, A., Tsaparas, N., Suki, W., and Eknoyan, G., 1972, Renal effects of lithium administration in rats: alterations in water and electrolyte metabolism and the response to vasopressin and cyclic adenosine monophosphate during prolonged administration, J. Lab. Clin. Med., 51:1081.Google Scholar
  81. McMartin, D.N., and Engel, S.G., 1982, Effect of aging on gentamicin nephrotoxicity and pharmacokinetics in the rat, Res. Commun. Clin. Pathol. Pharm., 38:193.Google Scholar
  82. Mihatsch, M.J., Thiel, G., Spichtin, H.P., 1983, Morphological findings in kidney transplants after treatment with cyclosporine, Transpl. Proc., 15:2821.Google Scholar
  83. Murray, B.M., Paller, M.S., Ferris, T.F., 1985, Effect of cyclosporine administration on renal haemodynamics in conscious rats, Kidney Int., 28:767.PubMedCrossRefGoogle Scholar
  84. Myers, B. D. , Ross, J., Newton, L., Luetscher, J., Perlroth, M., 1984, Cyclosporine associated chronic nephropathy, New Eng. J. Med., 311:699.PubMedCrossRefGoogle Scholar
  85. Myers, R.B., Morgan, T.O., Carney, S.L., and Ray. C., 1980, Effects of lithium on the kidney, Kidney Int., 18:601.PubMedCrossRefGoogle Scholar
  86. Palestine, A.G., Austin, H.A., Balow, J.E., Antonovych, T.T., Sabnis, S.G., Preuss, H.G., Nussenblatt, R.B., 1986, Renal histopathological alterations in patients treated with cyclosporine for uveitis, New Eng. J. Med., 314:129.CrossRefGoogle Scholar
  87. Parker, R.A., Bennett, W.M., Plamp, C.E., Houghton, C., Gilbert, D.N. and Porter, G.A., 1980, Resistance of female rats to gentamicin nephrotoxicity, Proc. 11th Int. Cong. Chemother. Antibiot., 1:601.Google Scholar
  88. Penney, M.D., Hullin, R.P., Srinivasan, D.P., and Morgan, D.B., 1981, The relationship between plasma lithium and renal responsiveness to arginine vasopressin in man, Clin. Sci., 61:793.PubMedGoogle Scholar
  89. Perico, N., Benigni, A., Zoja, C., Delaini, F., Remuzzi, G., 1985, Functional significance of exaggerated renal thromboxane A2 synthesis induced by cyclosporin A., Am. J. Physiol., 257:F581.Google Scholar
  90. Plenge, P., Mellerup, E.T., Bolurg, T.G., Burn, C., Hetmar, O., Ladefoged, J., Larsen, S., and Rafaelsen, O.J., 1982 Lithium treatment: does the kidney prefer one daily dose instead of two?, Acta Psvchiat. Scand., 66:121.CrossRefGoogle Scholar
  91. Porter, G.A., and Bennett, W.M., 1985, The effect of drugs on the kidney In: “Harrison’s Principles of Internal Medicine, Update VI: The New Treatment Modalities,” R.G. Petersorf, R.D. Adams, E. Braunwald, K.I. Isselbacher, J.B. Martin, and J.D. Wilson, ed., McGraw-Hill Inc., New York.Google Scholar
  92. Porter, G.A. and Bennett, W.M., 1986, Chronic cyclosporine associated nephropathy, Transpl. Proc., 18:204.Google Scholar
  93. Porter, G.A., and Bennett, W.M., 1986, Nephrotoxin-induced acute renal failure, In: Acute Renal Failure, Chap 6., B.M. Brenner, and J.F. Stein, ed., Churchill-Livingstone, New York, London.Google Scholar
  94. Porter, G.A., Bennett, W.M., and Gilbert, D.N., 1983, Unraveling aminoglycoside nephrotoxicity using animal models, J. Clin. Pharmacol., 23:445.PubMedGoogle Scholar
  95. Radomski, J.L., Fuyat, H.N., Nelson, A.A., and Smith, P.K., 1950, The toxic effects, excretion and distribution of lithium chloride, J. Pharmacol. Exp. Thera., 100:429.Google Scholar
  96. Ramsey, T.A. and Cox, M., 1982, Lithium and the kidney: A review. Am. J. Psvchiat., 4:139.Google Scholar
  97. Rogers, T.S., Elzinga, L., Bennett, W.M., Kelley, V.E., 1987, Selective enhancement of thromboxane in macrophages and kidneys in cyclosporine A induced nephrotoxicity: Dietary protection by fish oil. Transplantation (in press) .Google Scholar
  98. Schentag, J.J., Cerra, F.B., and Plaet, M.E. 1982, Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients, Antimicro. Agent. Chemother., 21:721 .CrossRefGoogle Scholar
  99. Schentag, J.J., Suften, T.A., and Plaut, M.E. 1978, Early detection of aminoglycoside nephrotoxicity with beta-2-microglobulin, J. Med., 9:201.PubMedGoogle Scholar
  100. Schou, M., Amdisen, A., Thomsen, K., Vestergaard, P., Hetmar, O., Mellerup, E.T., Plenge, P., and Rafaelsen, O.J., 1982, Lithium treatment regimen and renal water handling: the significance of dosage pattern and tablet type examined through comparison of the results of two clinics with different treatment regimens, Psvchopharmacol., 77:387.CrossRefGoogle Scholar
  101. Schou, M., Amdisen, A., and Trap-Jensen, J., 1986, Lithium poisoning, Am. J. Psvchiat., 124:520.Google Scholar
  102. Schwass, D., Sasaki, A., Houghton, D.C., Benner, K., Bennett, W.M., 1986, Effect of phenobarbital and cimetidine on experimental cyclosporine nephrotoxicity, Clin. Nephrol., 25:S126.Google Scholar
  103. Shemesh, O., Golbetz, H., Kriss, J. P. , Myers, B.D., 1985, Limitations of creatinine as a filtration marker in glomerulopathic patients, Kidney Int. , 28:830.PubMedCrossRefGoogle Scholar
  104. Shulman, H., Striker, G. , Deeg, H. J. , Kennedy, M., Storb, B., Thomas, E.D. , 1981, Nephrotoxicity of cyclosporin A after allogeneic marrow transplantation: glomerular thromboses and tubular injury, New Eng. J. Med., 305:1392 .PubMedCrossRefGoogle Scholar
  105. Singer, I., Rotenberg, D., and Puschett, J.B., 1972, Lithium-induced nephrogenic diabetes insipidus: In vivo and in vitro studies, J. Clin. Invest., 51:1081.PubMedCrossRefGoogle Scholar
  106. Smith, C.R. and Lietman, P.S., 1983, Effect of furosemide on aminoglycoside induced nephrotoxicity and auditory toxicity in humans, Antimicrob. Agents. Chemother., 213:133.CrossRefGoogle Scholar
  107. Smith, C.R., Lipsky, J.J., Lasker, O.L., and Lietman, P.S., 1980, Doubleblind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin, New Eng. J. Med, 302:1106PubMedCrossRefGoogle Scholar
  108. Steele, T.H. , Dudgeon, K.L., and Larmore, C.K., 1979, Pharmacological characterization of lithium reabsorption in the rat, J. Pharmacol. Exp. Ther., 196:188.Google Scholar
  109. Sugarman, A., Brown, R.S., Silvia, P., and Rosen, S., 1983, Features of gentamicin nephrotoxicity and effect of concurrent cephalothin in rats, Nephron, 34:239.PubMedCrossRefGoogle Scholar
  110. Textor, S.C., Fornan, S.J., Borer, W., Carlson, J., 1986, Sequential blood pressure hormonal and renal changes during bone marrow transplant recipients with normal renal function, Clin. Res., 34:44A.Google Scholar
  111. Thompson, K. and Schou, M., 1968, Renal lithium excretion in man, Am. J. Physiol., 215:823.Google Scholar
  112. Thurau, K., Mason, J., and Gstraunthaler, G., 1985, Experimental acute renal failure, In: “The Kidney”, Physiology and Pathophyisology, Chap. 81., pg. 1885. D.W. Seldew and G. Giebisch, ed., Raven Press, New York,Google Scholar
  113. Trollfars, B., 1983. Gentamicin-associated changes in renal function are reversible during continuous treatment, J. Antimicrob. Chemother., 12:285.CrossRefGoogle Scholar
  114. Tulkens, P.M., 1986, Experimental studies on nephrotoxicity of aminoglycosides at low doses: mechanisms and perspectives, Am. J. Med., 80:105PubMedCrossRefGoogle Scholar
  115. Tyrer, S. P. , Schacht, R.G., McCarthy, M. J. , Menard, K. N. , Leong S., and Shopsin, B., 1983, The effect of lithium on renal haemodynamic function, Psychol. Med., 13:61.PubMedCrossRefGoogle Scholar
  116. Vaamonde, C.A., Bier, R. T. , Grovea, W., Alpert, H, Kelley, J. and Pardo, V., 1984, Effect of duration of diabetes on the protection observed in the diabetic rat against gentamicin — induced acute renal failure, Miner. Electrol. Metab., 10:209.Google Scholar
  117. Von Graffenreid, B., Harrison, W.B., 1985, Renal function in autoimmune diseases treated with cyclosporine, Transp, Proc., 17:215.Google Scholar
  118. Walker, R.G., Bennett, W.M., Davies, B.M., and Kincaid-Smith, P., 1982, Structural and functional effects of long-term lithium therapy, Kidney Int. , 11:S13.Google Scholar
  119. Waller, D.G., Edwards, J. G. , Naik, R., and Polak, A., 1984, Renal function during lithium treatment, O. J. Med., 53:369.Google Scholar
  120. Waller, D.G. and George, C.F., 1984, Lithium and the kidney, Adv. Drug React. Ac. Pois. Rev., 3:65.Google Scholar
  121. Wallin, L., Alling, C., and Aurell, M., 1982, Impairment of renal function in patients on long-term lithium treatment, Clin. Nephrol., 18:23.PubMedGoogle Scholar
  122. Weinberg, J.M.,1986, The role of cell calcium overload in nephrotoxic renal tubular cell injury, Am. J. Kidney Dis., 8:284.PubMedGoogle Scholar
  123. Whelton, A and Solez, K., 1984, Sex and gentamicin-damaged kidneys, In: “Acute Renal Failure: Correlation Between Morphology and Function,” pg. 221, A. Welton, and K. Solez, ed., Marcel Dekker, New YorkGoogle Scholar
  124. Whiting, P.H., Thomson, A.W., Blair, J.T., Simpson, J.G., 1982, Experimental cyclosporin A nephrotoxicity, Br. J. Exp. Pathol., 63:88.PubMedGoogle Scholar
  125. Whiting, P.H., Thomson, A.W., Blair, J.T., Simpson, J.G., 1982, Experimental cyclosporin A nephrotoxicity, Br. J. Exp. Pathol., 63:88.PubMedGoogle Scholar
  126. Wood, C.A., Kohlhepp, S.J., Bennett, W.M., Porter, G.A., Houghton, D.C., Kohner, P . W . , Brummet, R., Gilbert, D . N . , 1987, The influence of tobramycin dosage regimen on nephrotoxicity, ototoxicity and antibacterial efficacy in a rat model of subcutaneous abscess, (submitted for publication) .Google Scholar
  127. Xue, H., Bukowski, R., McCarron, D.A., Bennett, W.M., 1987, Cyclosporin A induces contraction in isolated rat aorta, Transplantation, (in press).Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • George A. Porter
    • 1
  • William M. Bennett
    • 1
  1. 1.Department of MedicineOregon Health Sciences University PortlandUSA

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