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Mechanisms of Drug-Induced Nephrotoxicity

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Adverse Drug Reactions

Part of the book series: Handbook of Experimental Pharmacology ((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.

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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

  • Albaqumi M, Soos TJ, Barisoni L, Nelson PJ (2006) Collapsing glomerulopathy. J Am Soc Nephrol 17:2854–2863

    Article  PubMed  CAS  Google Scholar 

  • Barrett BJ, Parfrey PS (2006) Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med 354:379–386

    Article  PubMed  CAS  Google Scholar 

  • Braden GL, O'Shea MH, Mulhern JG (2005) Tubulointerstitial diseases. Am J Kidney Dis 46:560–572

    Article  PubMed  Google Scholar 

  • Brix AE (2002) Renal papillary necrosis. Toxicol Pathol 30:672–674

    Article  PubMed  CAS  Google Scholar 

  • Burdmann EA, Andoh TF, Yu L, Bennett WM (2003) Cyclosporine nephrotoxicity. Semin Nephrol 23:465–476

    Article  PubMed  CAS  Google Scholar 

  • 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 43:405–413

    Article  PubMed  CAS  Google Scholar 

  • Choudhury D, Ahmed Z (2006) Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol 2:80–91

    Article  PubMed  CAS  Google Scholar 

  • Costa S, Nucci M (2001) Can we decrease amphotericin nephrotoxicity? Curr Opin Crit Care 7:379–383

    Article  PubMed  CAS  Google Scholar 

  • Cosyns JP (2003) Aristolochic acid and ‘Chinese herbs nephropathy': a review of the evidence to date. Drug Saf 26:33–48

    Article  PubMed  CAS  Google Scholar 

  • Cuellar ML (2002) Drug-induced vasculitis. Curr Rheumatol Rep 4:55–59

    Article  PubMed  Google Scholar 

  • D'agati V (2003) Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol 23:117–134

    Article  PubMed  Google Scholar 

  • Daudon M, Jungers P (2004) Drug-induced renal calculi: epidemiology, prevention and management. Drugs 64:245–275

    Article  PubMed  Google Scholar 

  • De Broe ME, Elseviers MM (1998) Analgesic nephropathy. N Engl J Med 338:446–452

    Article  PubMed  Google Scholar 

  • de Mattos AM, Olyaei AJ, Bennett WM (2000) Nephrotoxicity of immunosuppressive drugs: long-term consequences and challenges for the future. Am J Kidney Dis 35:333–346

    Article  PubMed  Google Scholar 

  • Deray G (2002) Amphotericin B nephrotoxicity. J Antimicrob Chemother 49(Suppl 1):37–41

    Article  PubMed  CAS  Google Scholar 

  • Dlott JS, Danielson CF, Blue-Hnidy DE, McCarthy LJ (2004) Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review. Ther Apher Dial 8:102–111

    Article  PubMed  CAS  Google Scholar 

  • Elasy TA, Anderson RJ (1996) Changing demography of acute renal failure. Semin Dial 9:438–443

    Article  Google Scholar 

  • Epstein BJ (2004) Elevations in serum creatinine concentration: concerning or reassuring? Pharmacotherapy 24:697–702

    Article  PubMed  CAS  Google Scholar 

  • Eriksson U, Seifert B, Schaffner A (2001) Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. BMJ 322:579–582

    Article  PubMed  CAS  Google Scholar 

  • Fanos V, Cataldi L (2000) Amphotericin B-induced nephrotoxicity: a review. J Chemother 12:463–470

    PubMed  CAS  Google Scholar 

  • 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 130:101–106

    PubMed  Google Scholar 

  • Griffin MR, Yared A, Ray WA (2000) Nonsteroidal antiinflammatory drugs and acute renal failure in elderly persons. Am J Epidemiol 151:488–496

    Article  PubMed  CAS  Google Scholar 

  • Hartmann JT, Lipp HP (2003) Toxicity of platinum compounds. Expert Opin Pharmacother 4:889–901

    Article  PubMed  CAS  Google Scholar 

  • Izzedine H, Launay-Vacher V, Deray G (2005) Antiviral drug-induced nephrotoxicity. Am J Kidney Dis 45:804–817

    Article  PubMed  CAS  Google Scholar 

  • Izzedine H, Launay-Vacher V, Bourry E, Brocheriou I, Karie S, Deray G (2006) Drug-induced glomerulopathies. Expert Opin Drug Saf 5:95–106

    Article  PubMed  CAS  Google Scholar 

  • Jaffe JA, Kimmel PL (2006) Chronic nephropathies of cocaine and heroin abuse: A critical review. Clin J Am Soc Nephrol 1:655–667

    Article  PubMed  CAS  Google Scholar 

  • Kintzel PE (2001) Anticancer drug-induced kidney disorders. Drug Saf 24:19–38

    Article  PubMed  CAS  Google Scholar 

  • Liptak P, Ivanyi B (2006) Primer: Histopathology of calcineurin-inhibitor toxicity in renal allografts. Nat Clin Pract Nephrol 2:398–404

    Article  PubMed  CAS  Google Scholar 

  • Maeder M, Klein M, Fehr T, Rickli H (2004) Contrast nephropathy: review focusing on prevention. J Am Coll Cardiol 44:1763–1771

    Article  PubMed  Google Scholar 

  • Markowitz GS, Perazella MA (2005) Drug-induced renal failure: a focus on tubulointerstitial disease. Clin Chim Acta 351:31–47

    Article  PubMed  CAS  Google Scholar 

  • 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 11:1439–1448

    PubMed  CAS  Google Scholar 

  • 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 12:1164–1172

    PubMed  CAS  Google Scholar 

  • 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 16:3389–3396

    Article  PubMed  CAS  Google Scholar 

  • 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 32:392–400

    Article  PubMed  CAS  Google Scholar 

  • Mingeot-Leclercq MP, Tulkens PM (1999) Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 43:1003–1012

    PubMed  CAS  Google Scholar 

  • Murphy SW, Barrett BJ, Parfrey PS (2000) Contrast nephropathy. J Am Soc Nephrol 11:177–182

    PubMed  CAS  Google Scholar 

  • Nagai J, Takano M (2004) Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacokinet 19:159–170

    Article  PubMed  CAS  Google Scholar 

  • Nash K, Hafeez A, Hou S (2002) Hospital-acquired renal insufficiency. Am J Kidney Dis 39:930–936

    Article  PubMed  Google Scholar 

  • 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 349:931–940

    Article  PubMed  CAS  Google Scholar 

  • Olyaei AJ, de Mattos AM, Bennett WM (2001) Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies. Curr Opin Crit Care 7:384–389

    Article  PubMed  CAS  Google Scholar 

  • Orbach H, Tishler M, Shoenfeld Y (2004) Intravenous immunoglobulin and the kidney–a two-edged sword. Semin Arthritis Rheum 34:593–601

    Article  PubMed  CAS  Google Scholar 

  • Perazella MA (1999) Crystal-induced acute renal failure. Am J Med 106:459–465

    Article  PubMed  CAS  Google Scholar 

  • Perazella MA (2003) Drug-induced renal failure: update on new medications and unique mechanisms of nephrotoxicity. Am J Med Sci 325:349–362

    Article  PubMed  Google Scholar 

  • Perazella MA (2005) Drug-induced nephropathy: an update. Expert Opin Drug Saf 4:689–706

    Article  PubMed  CAS  Google Scholar 

  • Pisoni R, Ruggenenti P, Remuzzi G (2001) Drug-induced thrombotic microangiopathy: incidence, prevention and management. Drug Saf 24:491–501

    Article  PubMed  CAS  Google Scholar 

  • 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 64:585–592

    Article  PubMed  CAS  Google Scholar 

  • Reginster F, Jadoul M, van Ypersele DS (1997) Chinese herbs nephropathy presentation, natural history and fate after transplantation. Nephrol Dial Transplant 12:81–86

    Google Scholar 

  • Rossert J (2001) Drug-induced acute interstitial nephritis. Kidney Int 60:804–817

    Article  PubMed  CAS  Google Scholar 

  • Rudnick MR, Kesselheim A, Goldfarb S (2006) Contrast-induced nephropathy: how it develops, how to prevent it. Cleve Clin J Med 73:75–77

    Article  PubMed  Google Scholar 

  • Schetz M, Dasta J, Goldstein S, Golper T (2005) Drug-induced acute kidney injury. Curr Opin Crit Care 11:555–565

    Article  PubMed  Google Scholar 

  • Silva FG (2004) Chemical-induced nephropathy: a review of the renal tubulointerstitial lesions in humans. Toxicol Pathol 32(Suppl 2):71–84

    Article  PubMed  CAS  Google Scholar 

  • Slaughter RL, Cappelletty DM (1998) Economic impact of aminoglycoside toxicity and its prevention through therapeutic drug monitoring. Pharmacoeconomics 14:385–394

    Article  PubMed  CAS  Google Scholar 

  • Streetman DS, Nafziger AN, Destache CJ, Bertino AS Jr (2001) Individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity and fewer associated costs. Pharmacotherapy 21:443–451

    Article  PubMed  CAS  Google Scholar 

  • Taguchi T, Nazneen A, Abid MR, Razzaque MS (2005) Cisplatin-associated nephrotoxicity and pathological events. Contrib Nephrol 148:107–121

    Article  PubMed  CAS  Google Scholar 

  • ten Holder SM, Joy MS, Falk RJ (2002) Cutaneous and systemic manifestations of drug-induced vasculitis. Ann Pharmacother 36:130–147

    Article  PubMed  Google Scholar 

  • Thadhani R, Pascual M, Bonventre JV (1996) Acute renal failure. N Engl J Med 334:1448–1460

    Article  PubMed  CAS  Google Scholar 

  • Vanholder R, Sever MS, Erek E, Lameire N (2000) Rhabdomyolysis. J Am Soc Nephrol 11:1553–1561

    PubMed  CAS  Google Scholar 

  • Waybill MM, Waybill PN (2001) Contrast media-induced nephrotoxicity: identification of patients at risk and algorithms for prevention. J Vasc Interv Radiol 12:3–9

    Article  PubMed  CAS  Google Scholar 

  • Whelton A (1999) Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 106:13S–24S

    Article  PubMed  CAS  Google Scholar 

  • 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 11:1080–1086

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Kidney Research Institute Department of Medicine Division of Nephrology, University of Washington, Seattle, WA, USA

    Jonathan Himmelfarb (Professor of Medicine Joseph W. Eschbach Endowed Chair for Kidney Research Director)

Authors
  1. Thomas D. Nolin
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  2. Jonathan Himmelfarb
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Correspondence to Jonathan Himmelfarb .

Editor information

Editors and Affiliations

  1. Faculty of Pharmacy, University of Toronto, Toronto, Canada, M5S 2S2

    Jack Uetrecht (Professor of Pharmacy and Medicine, Canada Research Chair in Adverse Drug Reactions) (Professor of Pharmacy and Medicine, Canada Research Chair in Adverse Drug Reactions)

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Nolin, T.D., Himmelfarb, J. (2010). Mechanisms of Drug-Induced Nephrotoxicity. In: Uetrecht, J. (eds) Adverse Drug Reactions. Handbook of Experimental Pharmacology, vol 196. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00663-0_5

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