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Mechanisms of Drug-Induced Nephrotoxicity

  • Thomas D. Nolin
  • Jonathan HimmelfarbEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 196)

Abstract

Drug-induced nephrotoxicity is a common complication of several medications and diagnostic agents. It is seen in both inpatient and outpatient settings with variable presentations ranging from mild, reversible injury to advanced kidney disease. Manifestations of drug-induced nephrotoxicity include acid–base abnormalities, electrolyte imbalances, urine sediment abnormalities, proteinuria, pyuria, hematuria, and, most commonly, a decline in the glomerular filtration rate. The mechanisms of drug-induced nephrotoxicity may differ between various drugs or drug classes, and they are generally categorized based on the histological component of the kidney that is affected. Aminoglycoside antibiotics, radiocontrast media, conventional nonselective nonsteroidal anti-inflammatory drugs, and selective cyclooxygenase-2 inhibitors, amphotericin B, and angiotensin-converting enzyme inhibitors have been frequently implicated. This chapter reviews the clinical presentation and basic mechanisms of drug-induced nephrotoxicity.

Keywords

Nephrotoxicity Kidney disease Acute kidney injury 

Abbreviations

ACEI

Angiotensin-converting enzyme inhibitor

AIN

Allergic interstitial nephritis

AKI

Acute kidney injury

ANCA

Antineutrophil cytoplasmic antibody

ARB

Angiotensin II receptor blocker

ATN

Acute tubular necrosis

BUN

Blood urea nitrogen

CKD

Chronic kidney disease

COX

Cyclooxygenase

ESRD

End-stage renal disease

FSGS

Focal segmental glomerulosclerosis

GFR

Glomerular filtration rate

HIV

Human immunodeficiency virus

NSAID

Nonsteroidal anti-inflammatory drug

PGE2

Prostaglandin E2

References

  1. Albaqumi M, Soos TJ, Barisoni L, Nelson PJ (2006) Collapsing glomerulopathy. J Am Soc Nephrol 17:2854–2863PubMedCrossRefGoogle Scholar
  2. Barrett BJ, Parfrey PS (2006) Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med 354:379–386PubMedCrossRefGoogle Scholar
  3. Braden GL, O'Shea MH, Mulhern JG (2005) Tubulointerstitial diseases. Am J Kidney Dis 46:560–572PubMedCrossRefGoogle Scholar
  4. Brix AE (2002) Renal papillary necrosis. Toxicol Pathol 30:672–674PubMedCrossRefGoogle Scholar
  5. Burdmann EA, Andoh TF, Yu L, Bennett WM (2003) Cyclosporine nephrotoxicity. Semin Nephrol 23:465–476PubMedCrossRefGoogle Scholar
  6. Choi HK, Merkel PA, Walker AM, Niles JL (2000) Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum 43:405–413PubMedCrossRefGoogle Scholar
  7. Choudhury D, Ahmed Z (2006) Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol 2:80–91PubMedCrossRefGoogle Scholar
  8. Costa S, Nucci M (2001) Can we decrease amphotericin nephrotoxicity? Curr Opin Crit Care 7:379–383PubMedCrossRefGoogle Scholar
  9. Cosyns JP (2003) Aristolochic acid and ‘Chinese herbs nephropathy': a review of the evidence to date. Drug Saf 26:33–48PubMedCrossRefGoogle Scholar
  10. Cuellar ML (2002) Drug-induced vasculitis. Curr Rheumatol Rep 4:55–59PubMedCrossRefGoogle Scholar
  11. D'agati V (2003) Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol 23:117–134PubMedCrossRefGoogle Scholar
  12. Daudon M, Jungers P (2004) Drug-induced renal calculi: epidemiology, prevention and management. Drugs 64:245–275PubMedCrossRefGoogle Scholar
  13. De Broe ME, Elseviers MM (1998) Analgesic nephropathy. N Engl J Med 338:446–452PubMedCrossRefGoogle Scholar
  14. de Mattos AM, Olyaei AJ, Bennett WM (2000) Nephrotoxicity of immunosuppressive drugs: long-term consequences and challenges for the future. Am J Kidney Dis 35:333–346PubMedCrossRefGoogle Scholar
  15. Deray G (2002) Amphotericin B nephrotoxicity. J Antimicrob Chemother 49(Suppl 1):37–41PubMedCrossRefGoogle Scholar
  16. Dlott JS, Danielson CF, Blue-Hnidy DE, McCarthy LJ (2004) Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review. Ther Apher Dial 8:102–111PubMedCrossRefGoogle Scholar
  17. Elasy TA, Anderson RJ (1996) Changing demography of acute renal failure. Semin Dial 9:438–443CrossRefGoogle Scholar
  18. Epstein BJ (2004) Elevations in serum creatinine concentration: concerning or reassuring? Pharmacotherapy 24:697–702PubMedCrossRefGoogle Scholar
  19. Eriksson U, Seifert B, Schaffner A (2001) Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. BMJ 322:579–582PubMedCrossRefGoogle Scholar
  20. Fanos V, Cataldi L (2000) Amphotericin B-induced nephrotoxicity: a review. J Chemother 12:463–470PubMedGoogle Scholar
  21. Gonlusen G, Akgun H, Ertan A, Olivero J, Truong LD (2006) Renal failure and nephrocalcinosis associated with oral sodium phosphate bowel cleansing: clinical patterns and renal biopsy findings. Arch Pathol Lab Med 130:101–106PubMedGoogle Scholar
  22. Griffin MR, Yared A, Ray WA (2000) Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am J Epidemiol 151:488–496PubMedCrossRefGoogle Scholar
  23. Hartmann JT, Lipp HP (2003) Toxicity of platinum compounds. Expert Opin Pharmacother 4:889–901PubMedCrossRefGoogle Scholar
  24. Izzedine H, Launay-Vacher V, Deray G (2005) Antiviral drug-induced nephrotoxicity. Am J Kidney Dis 45:804–817PubMedCrossRefGoogle Scholar
  25. Izzedine H, Launay-Vacher V, Bourry E, Brocheriou I, Karie S, Deray G (2006) Drug-induced glomerulopathies. Expert Opin Drug Saf 5:95–106PubMedCrossRefGoogle Scholar
  26. Jaffe JA, Kimmel PL (2006) Chronic nephropathies of cocaine and heroin abuse: A critical review. Clin J Am Soc Nephrol 1:655–667PubMedCrossRefGoogle Scholar
  27. Kintzel PE (2001) Anticancer drug-induced kidney disorders. Drug Saf 24:19–38PubMedCrossRefGoogle Scholar
  28. Liptak P, Ivanyi B (2006) Primer: Histopathology of calcineurin-inhibitor toxicity in renal allografts. Nat Clin Pract Nephrol 2:398–404PubMedCrossRefGoogle Scholar
  29. Maeder M, Klein M, Fehr T, Rickli H (2004) Contrast nephropathy: review focusing on prevention. J Am Coll Cardiol 44:1763–1771PubMedCrossRefGoogle Scholar
  30. Markowitz GS, Perazella MA (2005) Drug-induced renal failure: a focus on tubulointerstitial disease. Clin Chim Acta 351:31–47PubMedCrossRefGoogle Scholar
  31. Markowitz GS, Radhakrishnan J, Kambham N, Valeri AM, Hines WH, D'Agati VD (2000) Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol 11:1439–1448PubMedGoogle Scholar
  32. Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, Kuhn JA, Dratch AD, D'Agati VD (2001) Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 12:1164–1172PubMedGoogle Scholar
  33. Markowitz GS, Stokes MB, Radhakrishnan J, D'Agati VD (2005) Acute phosphate nephropathy following oral sodium phosphate bowel purgative: an underrecognized cause of chronic renal failure. J Am Soc Nephrol 16:3389–3396PubMedCrossRefGoogle Scholar
  34. Maurice-Estepa L, Daudon M, Katlama C, Jouanneau C, Sazdovitch V, Lacour B, Beaufils H (1998) Identification of crystals in kidneys of AIDS patients treated with foscarnet. Am J Kidney Dis 32:392–400PubMedCrossRefGoogle Scholar
  35. Mingeot-Leclercq MP, Tulkens PM (1999) Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 43:1003–1012PubMedGoogle Scholar
  36. Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182PubMedGoogle Scholar
  37. Nagai J, Takano M (2004) Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacokinet 19:159–170PubMedCrossRefGoogle Scholar
  38. Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39:930–936PubMedCrossRefGoogle Scholar
  39. Ojo AO, Held PJ, Port FK, Wolfe RA, Leichtman AB, Young EW, Arndorfer J, Christensen L, Merion RM (2003) Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 349:931–940PubMedCrossRefGoogle Scholar
  40. Olyaei AJ, de Mattos AM, Bennett WM (2001) Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies. Curr Opin Crit Care 7:384–389PubMedCrossRefGoogle Scholar
  41. Orbach H, Tishler M, Shoenfeld Y (2004) Intravenous immunoglobulin and the kidney–a two-edged sword. Semin Arthritis Rheum 34:593–601PubMedCrossRefGoogle Scholar
  42. Perazella MA (1999) Crystal-induced acute renal failure. Am J Med 106:459–465PubMedCrossRefGoogle Scholar
  43. Perazella MA (2003) Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci 325:349–362PubMedCrossRefGoogle Scholar
  44. Perazella MA (2005) Drug-induced nephropathy: an update. Expert Opin Drug Saf 4:689–706PubMedCrossRefGoogle Scholar
  45. Pisoni R, Ruggenenti P, Remuzzi G (2001) Drug-induced thrombotic microangiopathy: incidence, prevention and management. Drug Saf 24:491–501PubMedCrossRefGoogle Scholar
  46. Presne C, Fakhouri F, Noel LH, Stengel B, Even C, Kreis H, Mignon F, Grunfeld JP (2003) Lithium-induced nephropathy: Rate of progression and prognostic factors. Kidney Int 64:585–592PubMedCrossRefGoogle Scholar
  47. Reginster F, Jadoul M, van Ypersele DS (1997) Chinese herbs nephropathy presentation, natural history and fate after transplantation. Nephrol Dial Transplant 12:81–86Google Scholar
  48. Rossert J (2001) Drug-induced acute interstitial nephritis. Kidney Int 60:804–817PubMedCrossRefGoogle Scholar
  49. Rudnick MR, Kesselheim A, Goldfarb S (2006) Contrast-induced nephropathy: how it develops, how to prevent it. Cleve Clin J Med 73:75–77PubMedCrossRefGoogle Scholar
  50. Schetz M, Dasta J, Goldstein S, Golper T (2005) Drug-induced acute kidney injury. Curr Opin Crit Care 11:555–565PubMedCrossRefGoogle Scholar
  51. Silva FG (2004) Chemical-induced nephropathy: a review of the renal tubulointerstitial lesions in humans. Toxicol Pathol 32(Suppl 2):71–84PubMedCrossRefGoogle Scholar
  52. Slaughter RL, Cappelletty DM (1998) Economic impact of aminoglycoside toxicity and its prevention through therapeutic drug monitoring. Pharmacoeconomics 14:385–394PubMedCrossRefGoogle Scholar
  53. Streetman DS, Nafziger AN, Destache CJ, Bertino AS Jr (2001) Individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity and fewer associated costs. Pharmacotherapy 21:443–451PubMedCrossRefGoogle Scholar
  54. Taguchi T, Nazneen A, Abid MR, Razzaque MS (2005) Cisplatin-associated nephrotoxicity and pathological events. Contrib Nephrol 148:107–121PubMedCrossRefGoogle Scholar
  55. ten Holder SM, Joy MS, Falk RJ (2002) Cutaneous and systemic manifestations of drug-induced vasculitis. Ann Pharmacother 36:130–147PubMedCrossRefGoogle Scholar
  56. Thadhani R, Pascual M, Bonventre JV (1996) Acute renal failure. N Engl J Med 334:1448–1460PubMedCrossRefGoogle Scholar
  57. Vanholder R, Sever MS, Erek E, Lameire N (2000) Rhabdomyolysis. J Am Soc Nephrol 11:1553–1561PubMedGoogle Scholar
  58. Waybill MM, Waybill PN (2001) Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention. J Vasc Interv Radiol 12:3–9PubMedCrossRefGoogle Scholar
  59. Whelton A (1999) Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 106:13S–24SPubMedCrossRefGoogle Scholar
  60. Wynckel A, Ebikili B, Melin JP, Randoux C, Lavaud S, Chanard J (1998) Long-term follow-up of acute renal failure caused by angiotensin converting enzyme inhibitors. Am J Hypertens 11:1080–1086PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Kidney Research Institute Department of Medicine Division of NephrologyUniversity of WashingtonSeattleUSA

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