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Pharmacological aspects of nephrotoxicity

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Clinical Nephrotoxins

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Conclusions

In the past, renal failure was a clear predisposing cause for an increased incidence of adverse drug reactions. Systematic studies of drug kinetics and drug sensitivity in renal failure have shown how patients with renal failure differ from metabolically normal patients. Generalizations developed from these studies have lead to the principles that enable one to individualize drug therapy for azotemic patients. Using these principles, one can make the response to drugs more predictable for the patient with renal failure. And more predictable means safer.

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References

  1. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG. Interaction of cytochrome P-450 3A inhibitors with Pglycoprotein. J Pharmacol Exp Ther 2002; 303: 323–332.

    Article  CAS  PubMed  Google Scholar 

  2. Cummins CL, Jacobsen W, Benet LZ. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002; 300: 1036–1045.

    Article  CAS  PubMed  Google Scholar 

  3. Dresser GK, Schwarz UI, Wilkinson GR, Kim RB. Coordinate induction of both cytochrome P-4503A and MDR1 by St John’s wort in healthy subjects. Clin Pharmacol Ther 2003; 73: 41–50.

    Article  CAS  PubMed  Google Scholar 

  4. Fleming I. Cytochrome P-450 enzymes in vascular homeostasis. Circulation Res 2001; 89: 753–762.

    CAS  PubMed  Google Scholar 

  5. Nebert DW, Russell DW. Clinical importance of the cytochromes P-450. Lancet 2002; 360: 1155–1162.

    Article  CAS  PubMed  Google Scholar 

  6. Yu Z, Huse LM, Adler P, Graham L, Ma J, Zeldin DC, Kroetz DL. Increased CYP2J expression and epoxyeicosatrienoic acid formation in spontaneously hypertensive rat kidney. Mol Pharmacol 2000; 57: 1011–1020.

    CAS  PubMed  Google Scholar 

  7. Holla VR, Makita K, Zaphiropoulos PG, Capdevila JH. The kidney cytochrome P-450 2C23 arachidonic acid epoxygenase is upregulated during dietary salt loading. J Clin Invest 1999; 104: 751–760.

    CAS  PubMed  Google Scholar 

  8. Renton KW. Alteration of drug biotransformation and elimination during infection and inflammation. Pharmacol Ther 2001; 92: 147–163.

    Article  CAS  PubMed  Google Scholar 

  9. Mancinelli LM, Frassetto L, Floren LC, Dressler D, Carrier S, Bekersky I, Benet LZ, Christians U. The pharmacokinetics and metabolic disposition of tacrolimus: a comparison across ethnic groups. Clin Pharmacol Ther 2001; 69: 24–31.

    Article  CAS  PubMed  Google Scholar 

  10. Weinshilboum R. Inheritance and drug response. New Engl J Med 2003; 348: 529–537.

    Article  PubMed  Google Scholar 

  11. Tanigawara Y. Role of P-glycoprotein in drug disposition. Ther Drug Monit 2000; 22: 137–140.

    Article  CAS  PubMed  Google Scholar 

  12. Dean M, Hamon Y, Chimini G. The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 2001; 42: 1007–1017.

    CAS  PubMed  Google Scholar 

  13. Stouch TR, Gudmundsson O. Progress in understanding the structure-activity relationships of P-glycoprotein. Adv Drug Deliv Rev 2002; 54: 315–328.

    Article  CAS  PubMed  Google Scholar 

  14. Benet LZ, Cummins CL. The drug efflux-metabolism alliance: biochemical aspects. Adv Drug Deliv Rev 2001; 50(suppl 1): S3–S11.

    CAS  PubMed  Google Scholar 

  15. Lin JH, Yamazaki M. Role of p-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinetics 2003; 42: 59–98.

    CAS  Google Scholar 

  16. Kullak-Ublick GA, Beuers U, Paumgartner G. Hepatobiliary transport. J Hepatol 2000; 32(suppl 1): 3–18.

    CAS  PubMed  Google Scholar 

  17. Fricker G, Miller DS. Relevance of multidrug resistance proteins for intestinal drug absorption in vitro and in vivo. Pharmacol Toxicol 2002; 90: 5–13.

    Article  CAS  PubMed  Google Scholar 

  18. Kurata Y, Ieiri I, Kimura M, Morita T, Irie S, Urae A, Ohdo S, Ohtani H, Sawada Y, Higuchi S, Otsubo K. Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein. Clin Pharmacol Ther 2002; 72: 209–219.

    Article  CAS  PubMed  Google Scholar 

  19. Siegmund W, Ludwig K, Giessmann T, Dazert P, Schroeder E, Sperker B, Warzok R, Kroemer HK, Cascorbi I. The effects of the human MDR1 genotype on the expression of duodenal P-glycoprotein and disposition of the probe drug talinolol. Clin Pharmacol Ther 2002; 72: 572–583.

    CAS  PubMed  Google Scholar 

  20. Johne A, Kopke K, Gerloff T, Mai I, Rietbrock S, Meisel C, Hoffmeyer S, Kerb R, Fromm MF, Brinkmann U, Eichelbaum M, Brockmoller J, Cascorbi I, Roots I. Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin Pharmacol Ther 2002; 72: 584–294.

    Article  CAS  PubMed  Google Scholar 

  21. Cummins CL, Wu CY, Benet LZ. Sex-related differences in the clearance of cytochrome P-450 3A4 substrates may be caused by P-glycoprotein. Clin Pharmacol Ther 2002; 72: 474–489.

    Article  CAS  PubMed  Google Scholar 

  22. Masereeuw R, Terlouw SA, van Aubel RA, Russel FG, Miller DS. Endothelin B receptor-mediated regulation of ATP-driven drug secretion in renal proximal tubule. Mol Pharmacol 2000; 57(1): 59–67.

    CAS  PubMed  Google Scholar 

  23. Terlouw SA, Masereeuw R, Russel FG, Miller DS. Nephrotoxicants induce endothelin release and signaling in renal proximal tubules: effect on drug efflux. Mol Pharmacol 2001; 59(6): 1433–1440.

    CAS  PubMed  Google Scholar 

  24. Miller DS. Xenobiotic export pumps, endothelin signaling, and tubular nephrotoxicants—a case of molecular hijacking. J Biochem Mol Toxicol 2002; 16(3): 121–127.

    Article  CAS  PubMed  Google Scholar 

  25. Jalava KM, Partanen J, Neuvonen PJ. Itraconazole decreases renal clearance of digoxin. Ther Drug Monit 1997; 19(6): 609–613.

    Article  CAS  PubMed  Google Scholar 

  26. Wakasugi H, Yano I, Ito T, Hashida T, Futami T, Nohara R, Sasayama S, Inui K. Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein. Clin Pharmacol Ther 1998; 64(1): 123–128

    Article  CAS  PubMed  Google Scholar 

  27. del Moral RG, Andujar M, Ramirez C, Gomez-Morales M, Masseroli M, Aguilar M, Olmo A, Arrebola F, Guillen M, Garcia-Chicano MJ, Nogales FF, O’Valle F. Chronic cyclosporin A nephrotoxicity, P-glycoprotein overexpression, and relationships with intrarenal angiotensin II deposits. Am J Pathol 1997; 151(6): 1705–1714.

    PubMed  Google Scholar 

  28. Miller DS, Fricker G, Drewe J. p-Glycoprotein-mediated transport of a fluorescent rapamycin derivative in renal proximal tubule. J Pharmacol Exp Ther 1997; 282(1): 440–444.

    CAS  PubMed  Google Scholar 

  29. Gutmann H, Fricker G, Drewe J, Toeroek M, Miller DS. Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. Mol Pharmacol 1999; 56(2): 383–389.

    CAS  PubMed  Google Scholar 

  30. Koziolek MJ, Riess R, Geiger H, Thevenod F, Hauser IA. Expression of multidrug resistance P-glycoprotein in kidney allografts from cyclosporine A-treated patients. Kidney Int 2001; 60(1): 156–166.

    Article  CAS  PubMed  Google Scholar 

  31. Hall SD, Thummel KE, Watkins PB, Lown KS, Benet LZ, Paine MF, Mayo RR, Turgeon DK, Bailey DG, Fontana RJ, Wrighton SA. Molecular and physical mechanisms of first-pass extraction. Drug Metab Dispos 1999; 27(2): 161–166.

    CAS  PubMed  Google Scholar 

  32. Doherty MM, Charman WN. The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism ? Clin Pharmacokinet 2002; 41(4): 235–253.

    Article  CAS  PubMed  Google Scholar 

  33. Barone GW, Gurley BJ, Ketel BL, Abul-Ezz SR. Herbal supplements: a potential for drug interactions in transplant recipients. Transplantation 2001; 71: 239–241.

    CAS  PubMed  Google Scholar 

  34. Muscari A, Puddu GM, Puddu P. Lipid-lowering drugs: are adverse effects predictable and reversible ? Cardiology 2002; 97: 115–121.

    Article  CAS  PubMed  Google Scholar 

  35. Vlahakos DV, Manginas A, Chilidou D, Zamanika C, Alilvizatos PA. Intraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treatad with simvastatin and cyclosporine. Transplantation 2002; 73: 1962–1964.

    CAS  PubMed  Google Scholar 

  36. Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc 2000; 75: 933–942.

    CAS  PubMed  Google Scholar 

  37. Flockhart DA, Tanus-Santos JE. Implications of cytochrome P450 interactions when prescribing medication for hypertension. Arch Intern Med 2002; 162: 405–412.

    Article  CAS  PubMed  Google Scholar 

  38. Craig RM, Murphy P, Gibson TP, Quintanilla A, Chao C, Cochrane C, Patterson A, Atkinson AJ. Kinetic analysis of D-xylose absorption in normal subjects and in patients with chronic renal failure. J Lab Clin Med 1983; 101: 496–506.

    CAS  PubMed  Google Scholar 

  39. Kunihara M, Nagai J, Murakami T, Takano M. Renal excretion of rhodamine 123, a P-glycoprotein substrate, in rats with glycerol-induced acute renal failure. J Pharm Pharmacol 1998; 50(10): 1161–1165.

    CAS  PubMed  Google Scholar 

  40. Huang ZH, Murakami T, Okochi A, Yumoto R, Nagai J, Takano M. Expression and function of P-glycoprotein in rats with glycerol-induced acute renal failure. Eur J Pharmacol 2000; 406(3): 453–460.

    Article  CAS  PubMed  Google Scholar 

  41. Veau C, Leroy C, Banide H, Auchere D, Tardivel S, Farinotti R, Lacour B. Effect of chronic renal failure on the expression and function of rat intestinal P-glycoprotein in drug excretion. Nephrol Dial Transplant 2001; 16(8): 1607–1614.

    CAS  PubMed  Google Scholar 

  42. Laouari D, Yang R, Veau C, Blanke I, Friedlander G. Two apical multidrug transporters, P-gp and MRP2, are differently altered in chronic renal failure. Am J Physiol Renal Physiol 2001; 280(4): F636–F645.

    CAS  PubMed  Google Scholar 

  43. Boobis SW. Alteration of plasma albumin in relation to decreased drug binding in uremia. Clin Pharmacol Ther 1978; 22: 147–153.

    Google Scholar 

  44. Matzke GR, Frye RF. Drug administration in patients with renal insufficiency. Drug Safety 1997; 16: 205–231.

    CAS  PubMed  Google Scholar 

  45. Reidenberg MM. The biotransformation of drugs in renal failure. Am J Med 1977; 62: 482–485.

    CAS  PubMed  Google Scholar 

  46. Gibson TP. Renal disease and drug metabolism: an overview. Am J Kidney Dis 1986; 8: 7–17.

    CAS  PubMed  Google Scholar 

  47. Wood AJJ, Zhou HH. Ethnic differences in drug disposition and responsiveness. Clin Pharmacokinetics 1991; 20: 350–373.

    CAS  Google Scholar 

  48. Brosen L. Recent developments in hepatic drug oxidation. Clin Pharmacokinet 1990; 18: 220–239.

    CAS  PubMed  Google Scholar 

  49. Reidenberg MM, Affrime M. Influence of disease on binding of drugs to plasma proteins. Ann NY Acad Sci 1973; 226: 115–126.

    CAS  PubMed  Google Scholar 

  50. Drayer DE. Pharmacologically active drug metabolites: therapeutic and toxic activities, plasma and urine data in man, accumulation in renal failure. Clin Pharmacokinet 1976; 1: 426–443.

    CAS  PubMed  Google Scholar 

  51. Drayer DE, Lowenthal DT, Woosley RL, Nies AS, Schwartz A, Reidenberg MM. Cumulation of N-acetyl procainamide, an active metabolite of procainamide, in patients with impaired renal function. Clin Pharmacol Ther 1977; 22: 63–69.

    CAS  PubMed  Google Scholar 

  52. Szeto HH, Inturrisi CE, Houde R, Saal S, Cheigh J, Reidenberg MM. Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure or cancer. Ann Intern Med 1977; 86: 738–741.

    CAS  PubMed  Google Scholar 

  53. Kaiko RF, Foley KM, Grabinski PY, Heidrich G, Rogers AG, Inturrisi CE, Reidenberg MM. Central nervous system excitatory effects of meperidine in cancer patients. Ann Neurology 1983; 13: 180–185.

    CAS  Google Scholar 

  54. Dettli L, Spring P, Ryter S. Multiple dose kinetics and drug dosage in patients with kidney disease. Acta Pharmacol Toxicol 1971; 29 (suppl 3): 211–224.

    CAS  Google Scholar 

  55. Dundee JW, Richards RK. Effect of azotemia upon the action of intravenous barbiturate anesthesia. Anesthesiology 1954; 15: 333–346.

    CAS  PubMed  Google Scholar 

  56. Mak RH, DeFronzo RA. Glucose and insulin metabolism in uremia. Nephron 1992; 61(4): 377–382.

    CAS  PubMed  Google Scholar 

  57. Hall SD, Thummel KE, Watkins PB, Lown KS, Benet LZ, Paine MF, Mayo RR, Turgeon DK, Bailey DG, Fontana RJ, Wrighton SA. Molecular and physical mechanisms of first-pass extraction. Drug Metab Dispos 1999; 27(2): 161–166.

    CAS  PubMed  Google Scholar 

  58. Lo A, Burckart GJ. P-glycoprotein and drug therapy in organ transplantation. J Clin Pharmacol 1999; 39(10): 995–1005.

    Article  CAS  PubMed  Google Scholar 

  59. van Gelder T, Klupp J, Sawamoto T, Christians U, Morris RE. ATP-binding cassette transporters and calcineurin inhibitors: potential clinical implications. Transplant Proc 2001; 33(3): 2420–2421.

    PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. University of Antwerp, Belgium

    Gert A. Verpooten & Philippe Jorens

  2. Weill Medical College of Cornell University, New York, USA

    Marcus M. Reidenberg

Authors
  1. Gert A. Verpooten
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  2. Philippe Jorens
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  3. Marcus M. Reidenberg
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Editor information

Editors and Affiliations

  1. Department of Nephrology and Hypertension, University of Antwerp, Belgium

    Marc E. de Broe

  2. Department of Medicine, The Oregon Health Sciences University, Portland, Oregon, USA

    George A. Porter

  3. Northwest Renal Clinic, Legacy Good Samaritan Hospital, Portland, Oregon, USA

    William M. Bennett

  4. Department of Nephrology and Hypertension, University of Antwerp, Belgium

    Gert A. Verpooten

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© 2003 Kluwer Academic Publishers

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Verpooten, G.A., Jorens, P., Reidenberg, M.M. (2003). Pharmacological aspects of nephrotoxicity. In: de Broe, M.E., Porter, G.A., Bennett, W.M., Verpooten, G.A. (eds) Clinical Nephrotoxins. Springer, Dordrecht. https://doi.org/10.1007/1-4020-2586-6_34

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  • DOI: https://doi.org/10.1007/1-4020-2586-6_34

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-1-4020-1277-8

  • Online ISBN: 978-1-4020-2586-0

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