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Drug-Induced Acute Kidney Injury

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Core Concepts in Acute Kidney Injury

Abstract

Drug-induced acute kidney injury (AKI) is a relatively common problem. Prescribed medications, over-the-counter drugs/substances, and diagnostic agents may alter kidney function. As the kidney filters, secretes, reabsorbs, biotransforms, and excretes many drugs, it is not surprising that acute kidney injury is an adverse effect. Drugs and their metabolites can lead to injury within all compartments of the kidney including the vasculature, glomerulus, tubules, and interstitium. Common forms of drug-induced AKI affecting the various renal compartments include thrombotic microangiopathy, membranous and minimal change/focal segmental glomerulosclerosis, acute tubular injury/necrosis, osmotic nephropathy, crystalline-induced AKI, and acute interstitial nephritis. Recognizing AKI syndromes that are associated with various agents can lead to early identification of potentially harmful drugs and therapeutic agents, reducing exposure in at-risk patients. Once identified, the medication or agent can be withheld or dose-reduced, thereby significantly impacting and potentially reducing the duration and severity of kidney injury.

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References

  1. Schetz M, Dasta J, Goldstein S, Golper T. Drug-induced acute kidney injury. Curr Opin Crit Care. 2005;11:555–65.

    Article  PubMed  Google Scholar 

  2. Choudhury D, Ahmed Z. Drug-induced nephrotoxicity. Med Clin North Am. 1997;81:705–17.

    Article  CAS  PubMed  Google Scholar 

  3. Leape LL, Brennan TA, Laird N, et al. The nature of adverse events in hospitalized patients. Results of the Harvard Medical Practice Study II. N Engl J Med. 1991;324:377–84.

    Article  CAS  PubMed  Google Scholar 

  4. Mehta RL, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: the PICARD experience. Kidney Int. 2004;66:1613–21.

    Article  PubMed  Google Scholar 

  5. Nash K, Hafeez A, Hou S. Hospital-acquired renal insufficiency. Am J Kidney Dis. 2002;39:930–6.

    Article  PubMed  Google Scholar 

  6. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.

    Article  CAS  PubMed  Google Scholar 

  7. Perazella MA. Renal vulnerability to drug toxicity. Clin J Am Soc Nephrol. 2009;4:1275–83.

    Article  CAS  PubMed  Google Scholar 

  8. Fanos V, Cataldi L. Renal transport of antibiotics and nephrotoxicity: a review. J Chemother. 2001;13:461–72.

    Article  CAS  PubMed  Google Scholar 

  9. Enomoto A, Endou H. Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin Exp Nephrol. 2005;9:195–205.

    Article  CAS  PubMed  Google Scholar 

  10. Nagai J, Takano M. Molecular aspects of renal handling of aminoglycosides and strategies for preventing the nephrotoxicity. Drug Metab Pharmacokinet. 2004;19:159–70.

    Article  CAS  PubMed  Google Scholar 

  11. Ciarimboli G, Ludwig T, Lang D, et al. Cisplatin nephrotoxicity is critically mediated via the human organic cation transporter 2. Am J Pathol. 2005;167:1477–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jerkic M, Vojvodic S, Lopez-Novoa JM. The mechanism of increased renal susceptibility to toxic substances in the elderly. Part I. The role of increased vasoconstriction. Int Urol Nephrol. 2001;32:539–47.

    Article  CAS  PubMed  Google Scholar 

  13. Singh NP, Ganguli A, Prakash A. Drug-induced kidney diseases. J Assoc Physicians India. 2003;51:970–9.

    CAS  PubMed  Google Scholar 

  14. Guo X, Nzerue C. How to prevent, recognize, and treat drug-induced nephrotoxicity. Cleveland Clin J Med. 2002;69:289–90, 293–284, 296–287 passim.

    Article  Google Scholar 

  15. Ciarimboli G, Koepsell H, Iordanova M, et al. Individual PKC-phosphorylation sites in organic cation transporter 1 determine substrate selectivity and transport regulation. J Am Soc Nephrol. 2005;16:1562–70.

    Article  CAS  PubMed  Google Scholar 

  16. Harty L, Johnson K, Power A. Race and ethnicity in the era of emerging pharmacogenomics. J Clin Pharmacol. 2006;46:405–7.

    Article  PubMed  Google Scholar 

  17. Perazella MA. Diagnosing drug-induced AIN in the hospitalized patient: a challenge for the clinician. Clin Nephrol. 2014;81:381–8.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Muriithi AK, Nasr SH, Leung N. Utility of urine eosinophils in the diagnosis of acute interstitial nephritis. Clin J Am Soc Nephrol. 2013;8:1857–62.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Smith ER, Cai MM, McMahon LP, Wright DA, Holt SG. The value of simultaneous measurements of urinary albumin and total protein in proteinuric patients. Nephrol Dial Transplant. 2012;27:1534–41.

    Article  CAS  PubMed  Google Scholar 

  20. Samarawickrama A, Cai M, Smith ER, et al. Simultaneous measurement of urinary albumin and total protein may facilitate decision-making in HIV-infected patients with proteinuria. HIV Med. 2012;13:526–32.

    CAS  PubMed  Google Scholar 

  21. Fogazzi GB, Verdesca S, Garigali G. Urinalysis: core curriculum 2008. Am J Kidney Dis. 2008;51:1052–67.

    Article  PubMed  Google Scholar 

  22. Perazella MA. The urine sediment as a biomarker of kidney disease. Am J Kidney Dis. 2015;66:748.

    Article  CAS  PubMed  Google Scholar 

  23. Fogazzi GB. Crystalluria: a neglected aspect of urinary sediment analysis. Nephrol Dial Transplant. 1996;11:379–87.

    Article  CAS  PubMed  Google Scholar 

  24. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med. 1984;310:563–72.

    Article  CAS  PubMed  Google Scholar 

  25. Schlondorff D. Renal complications of nonsteroidal anti-inflammatory drugs. Kidney Int. 1993;44:643–53.

    Article  CAS  PubMed  Google Scholar 

  26. Perazella MA. COX-2 selective inhibitors: analysis of the renal effects. Expert Opin Drug Saf. 2002;1:53–64.

    Article  CAS  PubMed  Google Scholar 

  27. Perazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am J Med. 2001;111:64–7.

    Article  CAS  PubMed  Google Scholar 

  28. Eras J, Perazella MA. NSAIDs and the kidney revisited: are selective cyclooxygenase-2 inhibitors safe? Am J Med Sci. 2001;321:181–90.

    Article  CAS  PubMed  Google Scholar 

  29. Nankivell BJ, Borrows RJ, Fung CL, O’Connell PJ, Chapman JR, Allen RD. Calcineurin inhibitor nephrotoxicity: longitudinal assessment by protocol histology. Transplantation. 2004;78:557–65.

    Article  CAS  PubMed  Google Scholar 

  30. Fellstrom B. Cyclosporine nephrotoxicity. Transplant Proc. 2004;36:220S–3S.

    Article  CAS  PubMed  Google Scholar 

  31. Navar LG, Harrison-Bernard LM, Imig JD, Wang CT, Cervenka L, Mitchell KD. Intrarenal angiotensin II generation and renal effects of AT1 receptor blockade. J Am Soc Nephrol. 1999;10(Suppl 12):S266–72.

    CAS  PubMed  Google Scholar 

  32. Brewster UC, Perazella MA. The renin-angiotensin-aldosterone system and the kidney: effects on kidney disease. Am J Med. 2004;116:263–72.

    Article  CAS  PubMed  Google Scholar 

  33. Lee KG, Loh HL, Tan CS. Spontaneous cholesterol crystal embolism—a rare cause of renal failure. Ann Acad Med Singapore. 2012;41:176–7.

    PubMed  Google Scholar 

  34. Hitti WA, Wali RK, Weinman EJ, Drachenberg C, Briglia A. Cholesterol embolization syndrome induced by thrombolytic therapy. Am J Cardiovasc Drugs. 2008;8:27–34.

    Article  PubMed  Google Scholar 

  35. Walter RB, Joerger M, Pestalozzi BC. Gemcitabine-associated hemolytic-uremic syndrome. Am J Kidney Dis. 2002;40:E16.

    Article  PubMed  Google Scholar 

  36. Fung MC, Storniolo AM, Nguyen B, Arning M, Brookfield W, Vigil J. A review of hemolytic uremic syndrome in patients treated with gemcitabine therapy. Cancer. 1999;85:2023–32.

    Article  CAS  PubMed  Google Scholar 

  37. Harper L, Savage CO. Pathogenesis of ANCA-associated systemic vasculitis. J Pathol. 2000;190:349–59.

    Article  CAS  PubMed  Google Scholar 

  38. Gao Y, Zhao MH. Review article: drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrology. 2009;14:33–41.

    Article  CAS  PubMed  Google Scholar 

  39. Markowitz GS, Bomback AS, Perazella MA. Drug-induced glomerular disease: direct cellular injury. Clin J Am Soc Nephrol. 2015;10:1291–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hofstra JM, Debiec H, Short CD, et al. Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol. 2012;23:1735–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hogan JJ, Markowitz GS, Radhakrishnan J. Drug-induced glomerular disease: immune-mediated injury. Clin J Am Soc Nephrol. 2015;10:1300–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Perazella MA, Markowitz GS. Drug-induced acute interstitial nephritis. Nat Rev Nephrol. 2010;6:461–70.

    Article  CAS  PubMed  Google Scholar 

  43. Pirani CL, Valeri A, D’Agati V, Appel GB. Renal toxicity of nonsteroidal anti-inflammatory drugs. Contrib Nephrol. 1987;55:159–75.

    Article  CAS  PubMed  Google Scholar 

  44. Alper AB Jr, Meleg-Smith S, Krane NK. Nephrotic syndrome and interstitial nephritis associated with celecoxib. Am J Kidney dis. 2002;40:1086–90.

    Article  PubMed  Google Scholar 

  45. Brewster UC, Perazella MA. Proton pump inhibitors and the kidney: critical review. Clin Nephrol. 2007;68:65–72.

    Article  CAS  PubMed  Google Scholar 

  46. Brewster UC, Perazella MA. Acute kidney injury following proton pump inhibitor therapy. Kidney Int. 2007;71:589–93.

    Article  CAS  PubMed  Google Scholar 

  47. Geevasinga N, Coleman PL, Webster AC, Roger SD. Proton pump inhibitors and acute interstitial nephritis. Clin Gastroenterol Hepatol. 2006;4:597–604.

    Article  CAS  PubMed  Google Scholar 

  48. Perazella MA. Drug-induced nephropathy: an update. Expert Opin Drug Saf. 2005;4:689–706.

    Article  CAS  PubMed  Google Scholar 

  49. Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 2011;79:33–45.

    Article  CAS  PubMed  Google Scholar 

  50. Dickenmann M, Oettl T, Mihatsch MJ. Osmotic nephrosis: acute kidney injury with accumulation of proximal tubular lysosomes due to administration of exogenous solutes. Am J Kidney Dis. 2008;51:491–503.

    Article  PubMed  Google Scholar 

  51. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. N Engl J Med. 2012;367:124–34.

    Article  CAS  PubMed  Google Scholar 

  52. Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367:1901–11.

    Article  CAS  PubMed  Google Scholar 

  53. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins. 2010;2:2490–518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zaidan M, Lescure FX, Brocheriou I, et al. Tubulointerstitial nephropathies in HIV-infected patients over the past 15 years: a clinico-pathological study. Clin J Am Soc Nephrol. 2013;8:930–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Herlitz LC, Mohan S, Stokes MB, Radhakrishnan J, D’Agati VD, Markowitz GS. Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities. Kidney Int. 2010;78:1171–7.

    Article  CAS  PubMed  Google Scholar 

  56. Perazella MA. Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy. Kidney Int. 2010;78:1060–3.

    Article  CAS  PubMed  Google Scholar 

  57. Luciano RL, Perazella MA. Crystalline-induced kidney disease: a case for urine microscopy. Clin Kidney J. 2015;8:131–6.

    Article  CAS  PubMed  Google Scholar 

  58. Yarlagadda SG, Perazella MA. Drug-induced crystal nephropathy: an update. Expert Opin Drug Saf. 2008;7:147–58.

    Article  CAS  PubMed  Google Scholar 

  59. Fleischer R, Johnson M. Acyclovir nephrotoxicity: a case report highlighting the importance of prevention, detection, and treatment of acyclovir-induced nephropathy. Case Rep Med. 2010;2010:1.

    Article  Google Scholar 

  60. Chaudhari D, Crisostomo C, Ganote C, Youngberg G. Acute oxalate nephropathy associated with orlistat: a case report with a review of the literature. Case Rep Nephrol. 2013;2013:124604.

    PubMed  PubMed Central  Google Scholar 

  61. Singh A, Sarkar SR, Gaber LW, Perazella MA. Acute oxalate nephropathy associated with orlistat, a gastrointestinal lipase inhibitor. Am J Kidney Dis. 2007;49:153–7.

    Article  CAS  PubMed  Google Scholar 

  62. Perazella MA, Moeckel GW. Nephrotoxicity from chemotherapeutic agents: clinical manifestations, pathobiology, and prevention/therapy. Semin Nephrol. 2010;30:570–81.

    Article  CAS  PubMed  Google Scholar 

  63. Widemann BC, Balis FM, Kim A, et al. Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol. 2010;28:3979–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Chang HR, Pella PM. Atazanavir urolithiasis. N Engl J Med. 2006;355:2158–9.

    Article  CAS  PubMed  Google Scholar 

  65. Pacanowski J, Poirier JM, Petit I, Meynard JL, Girard PM. Atazanavir urinary stones in an HIV-infected patient. AIDS. 2006;20:2131.

    Article  PubMed  Google Scholar 

  66. Jao J, Wyatt CM. Antiretroviral medications: adverse effects on the kidney. Adv Chronic Kidney Dis. 2010;17:72–82.

    Article  PubMed  Google Scholar 

  67. Couzigou C, Daudon M, Meynard JL, et al. Urolithiasis in HIV-positive patients treated with atazanavir. Clin Infect Dis. 2007;45:e105–8.

    Article  CAS  PubMed  Google Scholar 

  68. Daudon M, Jungers P. Drug-induced renal calculi: epidemiology, prevention and management. Drugs. 2004;64:245–75.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA

    Randy L. Luciano

  2. Section of Nephrology, Yale University School of Medicine, New Haven, CT, USA

    Mark A. Perazella

  3. Department of Medicine, Yale University, New Haven, CT, USA

    Mark A. Perazella

Authors
  1. Randy L. Luciano
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  2. Mark A. Perazella
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Corresponding author

Correspondence to Mark A. Perazella .

Editor information

Editors and Affiliations

  1. Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Sushrut S. Waikar

  2. University College Dublin, Dublin, Ireland

    Patrick T. Murray

  3. Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Ajay K. Singh

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Luciano, R.L., Perazella, M.A. (2018). Drug-Induced Acute Kidney Injury. In: Waikar, S., Murray, P., Singh, A. (eds) Core Concepts in Acute Kidney Injury. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-8628-6_9

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  • DOI: https://doi.org/10.1007/978-1-4939-8628-6_9

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