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Drug-associated renal dysfunction and injury

Nature Clinical Practice Nephrology volume 2, pages 80–91 (2006)Cite this article

Abstract

Renal dysfunction and injury secondary to medications are common, and can present as subtle injury and/or overt renal failure. Some drugs perturb renal perfusion and induce loss of filtration capacity. Others directly injure vascular, tubular, glomerular and interstitial cells, such that specific loss of renal function leads to clinical findings, including microangiopathy, Fanconi syndrome, acute tubular necrosis, acute interstitial nephritis, nephrotic syndrome, obstruction, nephrogenic diabetes insipidus, electrolyte abnormalities and chronic renal failure. Understanding the mechanisms involved, and recognizing the clinical presentations of renal dysfunction arising from use of commonly prescribed medications, are important if injury is to be detected early and prevented. This article reviews the clinical features and basic processes underlying renal injury related to the use of common drugs.

Key Points

  • Renal injury caused by medication can usually be reversed if detected early

  • Drug-induced renal damage can be acute or chronic, prerenal, intrarenal (vascular, tubular, glomerular or interstitial) or postrenal

  • Different drug classes share common mechanisms of inducing renal injury (e.g. toxic, ischemic, inflammatory, obstructive or volume depletion)

  • Electrolyte/acid–base abnormalities are common effects of some medications

  • Medications that can cause kidney damage include diuretics, antihypertensives, immunosuppressants, antiplatelet agents, antivirals, chemotherapeutics, antibiotics and radiocontrast agents

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References

  1. Han WK and Bonventre JV (2004) Biologic markers for the early detection of acute kidney injury. Curr Opin Crit Care 10: 476–482

    Article  PubMed  Google Scholar 

  2. Kleinknecht D et al. (1987) Drug-associated acute renal failure: a prospective collaborative study of 81 biopsied patients. Adv Exp Med Biol 212: 125–128

    Article  CAS  PubMed  Google Scholar 

  3. Kaloyandes GJ et al. (2001) Antibiotic and Immunosupression-Related Renal Failure. Philadelphia: Lippincott, Williams & Wilkins

    Google Scholar 

  4. Kleinknecht D (1995) Interstitial nephritis, the nephrotic syndrome, and chronic renal failure secondary to nonsteroidal anti-inflammatory drugs. Semin Nephrol 15: 228–235

    CAS  PubMed  Google Scholar 

  5. Klinkhoff AV and Teufel A (1997) Reinstitution of gold after gold induced proteinuria. J Rheumatol 24: 1277–1279

    CAS  PubMed  Google Scholar 

  6. Wilcox CS (1999) Metabolic and adverse effects of diuretics. Semin Nephrol 19: 557–568

    CAS  PubMed  Google Scholar 

  7. Ellison DH (2001) Diuretic therapy and resistance in congestive heart failure. Cardiology 96: 132–143

    Article  CAS  PubMed  Google Scholar 

  8. Fliser D (1996) Loop diuretics and thiazides—the case for their combination in chronic renal failure. Nephrol Dial Transplant 11: 408–410

    CAS  PubMed  Google Scholar 

  9. Sandhofer A et al. (2002) Severe electrolyte disturbances and renal failure in elderly patients with combined diuretic therapy including xipamid. Wien Klin Wochenschr 114: 938–942

    CAS  PubMed  Google Scholar 

  10. Suki WN (1997) Use of diuretics in chronic renal failure. Kidney Int 59 (Suppl): S33–S35

    CAS  Google Scholar 

  11. Cruz J et al. (2004) Successful use of the new high-dose mannitol treatment in patients with Glasgow Coma Scale scores of 3 and bilateral abnormal pupillary widening: a randomized trial. J Neurosurg 100: 376–383

    Article  PubMed  Google Scholar 

  12. Ejaz P et al. (2004) NSAIDs and kidney. J Assoc Physicians India 52: 632–640

    CAS  PubMed  Google Scholar 

  13. Nankivell BJ et al. (2004) Oral cyclosporine but not tacrolimus reduces renal transplant blood flow. Transplantation 77: 1457–1459

    Article  CAS  PubMed  Google Scholar 

  14. Olyaei AJ et al. (2001) Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies. Curr Opin Crit Care 7: 384–389

    Article  CAS  PubMed  Google Scholar 

  15. Fang LS et al. (1980) Low fractional excretion of sodium with contrast media-induced acute renal failure. Arch Intern Med 140: 531–533

    Article  CAS  PubMed  Google Scholar 

  16. Van Buren D et al. (1985) De novo hemolytic uremic syndrome in renal transplant recipients immunosuppressed with cyclosporine. Surgery 98: 54–62

    CAS  PubMed  Google Scholar 

  17. Bren A et al. (2005) Follow-up of kidney graft recipients with cyclosporine-associated hemolytic-uremic syndrome and thrombotic microangiopathy. Transplant Proc 37: 1889–1891

    Article  CAS  PubMed  Google Scholar 

  18. Abraham KA et al. (2000) Hemolytic–uremic syndrome in association with both cyclosporine and tacrolimus. Transpl Int 13: 443–447

    Article  CAS  PubMed  Google Scholar 

  19. Lin CC et al. (2003) Tacrolimus-associated hemolytic uremic syndrome: a case analysis. J Nephrol 16: 580–585

    PubMed  Google Scholar 

  20. Abramowicz D et al. (1992) Induction of thromboses within renal grafts by high-dose prophylactic OKT3. Lancet 339: 777–778

    Article  CAS  PubMed  Google Scholar 

  21. Medina PJ et al. (2001) Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol 8: 286–293

    Article  CAS  PubMed  Google Scholar 

  22. Chinnakotla S et al. (2000) Clopidogrel-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in a kidney/pancreas transplant recipient. Transplantation 70: 550–552

    Article  CAS  PubMed  Google Scholar 

  23. Izzedine H et al. (2005) Antiviral drug-induced nephrotoxicity. Am J Kidney Dis 45: 804–817

    Article  CAS  PubMed  Google Scholar 

  24. Jackson AM et al. (1984) Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. Ann Intern Med 101: 41–44

    Article  CAS  PubMed  Google Scholar 

  25. Giroux L et al. (1985) Mitomycin-C nephrotoxicity: a clinico-pathologic study of 17 cases. Am J Kidney Dis 6: 28–39

    Article  CAS  PubMed  Google Scholar 

  26. Pisoni R et al. (2001) Drug-induced thrombotic microangiopathy: incidence, prevention and management. Drug Saf 24: 491–501

    Article  CAS  PubMed  Google Scholar 

  27. Venkat KK et al. (1991) Reversal of cyclosporine-associated hemolytic–uremic syndrome by plasma exchange with fresh-frozen plasma replacement in renal transplant recipients. Transplant Proc 23: 1256–1257

    CAS  PubMed  Google Scholar 

  28. Trimarchi HM et al. (1999) FK506-associated thrombotic microangiopathy: report of two cases and review of the literature. Transplantation 67: 539–544

    Article  CAS  PubMed  Google Scholar 

  29. Price TM et al. (1985) Renal failure and hemolytic anemia associated with mitomycin C. A case report. Cancer 55: 51–56

    Article  CAS  PubMed  Google Scholar 

  30. Garibotto G et al. (1989) Successful treatment of mitomycin C-associated hemolytic uremic syndrome by plasmapheresis. Nephron 51: 409–412

    Article  CAS  PubMed  Google Scholar 

  31. Ponticelli C et al. (1977) Late recovery of renal function in a woman with the hemolytic uremic syndrome. Clin Nephrol 8: 367–370

    CAS  PubMed  Google Scholar 

  32. Hauglustaine D et al. (1981) Oestrogen containing oral contraceptives, decreased prostacyclin production, and haemolytic uraemic syndrome. Lancet 1: 328–329

    Article  CAS  PubMed  Google Scholar 

  33. Ruggenenti P and Remuzzi G (1990) Thrombotic thrombocytopenic purpura and related disorders. Hematol Oncol Clin North Am 4: 219–241

    Article  CAS  PubMed  Google Scholar 

  34. Berns JS et al. (1992) Inherited hemolytic uremic syndrome in adults. Am J Kidney Dis 19: 331–334

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  36. Walter RB et al. (2002) Gemcitabine-associated hemolytic–uremic syndrome. Am J Kidney Dis 40: E16

    Article  PubMed  Google Scholar 

  37. Hitti WA and Anderson J (2005) Cholesterol emboli-induced renal failure and gastric ulcer after thrombolytic therapy. South Med J 98: 235–237

    Article  PubMed  Google Scholar 

  38. Ben-Chitrit S et al. (1994) Cholesterol embolization syndrome following thrombolytic therapy with streptokinase and tissue plasminogen activator. Nephrol Dial Transplant 9: 428–430

    CAS  PubMed  Google Scholar 

  39. Eliot RS et al. (1964) Atheromatous Embolism. Circulation 30: 611–618

    Article  CAS  PubMed  Google Scholar 

  40. Pennington M et al. (2002) Cholesterol embolization syndrome: cutaneous histopathological features and the variable onset of symptoms in patients with different risk factors. Br J Dermatol 146: 511–517

    Article  CAS  PubMed  Google Scholar 

  41. Fine MJ et al. (1987) Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology 38: 769–784

    Article  CAS  PubMed  Google Scholar 

  42. Lameire N et al. (2005) Acute renal failure. Lancet 365: 417–430

    Article  CAS  PubMed  Google Scholar 

  43. Edelstein CL and Schrier R (2001) Pathophysiology of Ischemic Acute Renal Injury. Philadelphia: Lippincott, Williams & Wilkins

    Google Scholar 

  44. Henrich WL (2005) Nephrotoxicity of several newer agents. Kidney Int 67 (Suppl): S107–S109

    Article  Google Scholar 

  45. Ho ES et al. (2000) Cytotoxicity of antiviral nucleotides adefovir and cidofovir is induced by the expression of human renal organic anion transporter 1. J Am Soc Nephrol 11: 383–393

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  47. Kaloyanides GJ and Pastoriza-Munoz E (1980) Aminoglycoside nephrotoxicity. Kidney Int 18: 571–582

    Article  CAS  PubMed  Google Scholar 

  48. Cronin RE and Henrich WL (1996) Toxic Nephropathy. Philadelphia: WB Saunders

    Google Scholar 

  49. Maher J (1991) Toxic Nephropathies. Boston: Kluwer Academic Publishers

    Book  Google Scholar 

  50. Patel R and Savage A (1979) Symptomatic hypomagnesemia associated with gentamicin therapy. Nephron 23: 50–52

    Article  CAS  PubMed  Google Scholar 

  51. Taguchi T et al. (2005) Cisplatin-associated nephrotoxicity and pathological events. Contrib Nephrol 148: 107–121

    Article  CAS  PubMed  Google Scholar 

  52. Uehara T et al. (2005) Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a comparative study with cisplatin in rats. Arch Toxicol 79: 451–460

    Article  CAS  PubMed  Google Scholar 

  53. Markowitz GS et al. (2003) Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int 64: 281–289

    Article  CAS  PubMed  Google Scholar 

  54. Hiroi-Furuya E et al. (1999) Etidronate (EHDP) inhibits osteoclastic-bone resorption, promotes apoptosis and disrupts actin rings in isolate-mature osteoclasts. Calcif Tissue Int 64: 219–223

    Article  CAS  PubMed  Google Scholar 

  55. Markowitz G et al. (2001) Collapsing focal segmental glomerulosclerosis following treatment with high dose pamidronate. J Am Soc Nephrol 12: 1164–1172

    CAS  PubMed  Google Scholar 

  56. Orbach H et al. (2004) Intravenous immunoglobulin and the kidney—a two-edged sword. Semin Arthritis Rheum 34: 593–601

    Article  CAS  PubMed  Google Scholar 

  57. Khalil M et al. (2000) Macrophagelike vacuolated renal tubular cells in the urine of a male with osmotic nephrosis associated with intravenous immunoglobulin therapy: a case report. Acta Cytol 44: 86–90

    Article  CAS  PubMed  Google Scholar 

  58. Visweswaran P et al. (1997) Mannitol-induced acute renal failure. J Am Soc Nephrol 8: 1028–1033

    CAS  PubMed  Google Scholar 

  59. Ferraboli R et al. (1997) Anuric acute renal failure caused by dextran 40 administration. Ren Fail 19: 303–306

    Article  CAS  PubMed  Google Scholar 

  60. Erdbruegger U et al. (2004) Quiz page: tubular epithelial injury consistent with osmotic nephrosis. Am J Kidney Dis 44: e1

    Article  Google Scholar 

  61. De Labarthe A et al. (2001) Acute renal failure secondary to hydroxyethylstarch administration in a surgical patient. Am J Med 111: 417–418

    Article  CAS  PubMed  Google Scholar 

  62. Hansen-Schmidt S et al. (1996) Osmotic nephrosis due to high-dose immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin A nephritis. Am J Kidney Dis 28: 451–453

    Article  CAS  PubMed  Google Scholar 

  63. Gossmann J et al. (2001) Pathophysiology of cyclosporine-induced nephrotoxicity in humans: a role for nitric oxide? Kidney Blood Press Res 24: 111–115

    Article  CAS  PubMed  Google Scholar 

  64. Andoh TF et al. (1996) Comparison of acute rapamycin nephrotoxicity with cyclosporine and FK506. Kidney Int 50: 1110–1117

    Article  CAS  PubMed  Google Scholar 

  65. Gibbs WJ et al. (2005) Liposomal amphotericin B: clinical experience and perspectives. Expert Rev Anti Infect Ther 3: 167–181

    Article  CAS  PubMed  Google Scholar 

  66. Porter GA (1989) Contrast-associated nephropathy. Am J Cardiol 64: 22E–26E

    Article  CAS  PubMed  Google Scholar 

  67. Mueller C et al. (2002) Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 162: 329–336

    Article  CAS  PubMed  Google Scholar 

  68. Briguori C et al. (2005) New pharmacological protocols to prevent or reduce contrast media nephropathy. Minerva Cardioangiol 53: 49–58

    CAS  PubMed  Google Scholar 

  69. Tepel M et al. (2000) Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med 343: 180–184

    Article  CAS  PubMed  Google Scholar 

  70. Stone GW et al. (2003) Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial. JAMA 290: 2284–2291

    Article  CAS  PubMed  Google Scholar 

  71. Vogt B et al. (2001) Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful. Am J Med 111: 692–698

    Article  CAS  PubMed  Google Scholar 

  72. Marenzi G et al. (2003) The prevention of radiocontrast-agent-induced nephropathy by hemofiltration. N Engl J Med 349: 1333–1340

    Article  CAS  PubMed  Google Scholar 

  73. Kancha K et al. (2004) Hemofiltration and the prevention of radiocontrast-agent-induced nephropathy. N Engl J Med 350: 836–838; author reply 836–838

    Article  CAS  PubMed  Google Scholar 

  74. Forman JP (2004) Hemofiltration and the prevention of radiocontrast-agent-induced nephropathy. N Engl J Med 350: 836–838; author reply 836–838

    Article  PubMed  Google Scholar 

  75. Sam AD II et al. (2003) Safety of gadolinium contrast angiography in patients with chronic renal insufficiency. J Vasc Surg 38: 313–318

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  77. Baylor P and Williams K (1999) Interstitial nephritis, thrombocytopenia, hepatitis, and elevated serum amylase levels in a patient receiving clarithromycin therapy. Clin Infect Dis 29: 1350–1351

    Article  CAS  PubMed  Google Scholar 

  78. Tintillier M et al. (2004) Telithromycin-induced acute interstitial nephritis: a first case report. Am J Kidney Dis 44: e25–e27

    Article  PubMed  Google Scholar 

  79. Szalat A et al. (2004) Acute renal failure and interstitial nephritis in a patient treated with rofecoxib: case report and review of the literature. Arthritis Rheum 51: 670–673

    Article  PubMed  Google Scholar 

  80. Ra A and Tobe SW (2004) Acute interstitial nephritis due to pantoprazole. Ann Pharmacother 38: 41–45

    Article  PubMed  Google Scholar 

  81. Clarkson MR et al. (2004) Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant 19: 2778–2783

    Article  CAS  PubMed  Google Scholar 

  82. Clive DM and Stoff JS (1984) Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 310: 563–572

    Article  CAS  PubMed  Google Scholar 

  83. Hanabusa H et al. (1999) Renal atrophy associated with long-term treatment with indinavir. N Engl J Med 340: 392–393

    Article  CAS  PubMed  Google Scholar 

  84. Martinez F et al. (1998) Indinavir crystal deposits associated with tubulointerstitial nephropathy. Nephrol Dial Transplant 13: 750–753

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  86. Demko TM et al. (1997) Obstructive nephropathy as a result of retroperitoneal fibrosis: a review of its pathogenesis and associations. J Am Soc Nephrol 8: 684–688

    CAS  PubMed  Google Scholar 

  87. Waters VV (1989) Hydralazine, hydrochlorothiazide and ampicillin associated with retroperitoneal fibrosis: case report. J Urol 141: 936–937

    Article  CAS  PubMed  Google Scholar 

  88. Iversen BM et al. (1975) Retroperitoneal fibrosis during treatment with methydopa. Lancet 2: 302–304

    Article  CAS  PubMed  Google Scholar 

  89. Damstrup L and Jensen TT (1986) Retroperitoneal fibrosis after long-term daily use of ergotamine. Int Urol Nephrol 18: 299–301

    Article  CAS  PubMed  Google Scholar 

  90. Perneger TV et al. (1994) Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal antiinflammatory drugs. N Engl J Med 331: 1675–1679

    Article  CAS  PubMed  Google Scholar 

  91. Nanra RS et al. (1978) Analgesic nephropathy: etiology, clinical syndrome, and clinicopathologic correlations in Australia. Kidney Int 13: 79–92

    Article  CAS  PubMed  Google Scholar 

  92. Gloor FJ (1978) Changing concepts in pathogenesis and morphology of analgesic nephropathy as seen in Europe. Kidney Int 13: 27–33

    Article  CAS  PubMed  Google Scholar 

  93. Kincaid-Smith P (1980) Analgesic abuse and the kidney. Kidney Int 17: 250–260

    Article  Google Scholar 

  94. Bach PH and Hardy TL (1985) Relevance of animal models to analgesic-associated renal papillary necrosis in humans. Kidney Int 28: 605–613

    Article  CAS  PubMed  Google Scholar 

  95. Akhund L et al. (2003) Celecoxib-related renal papillary necrosis. Arch Intern Med 163: 114–115

    Article  PubMed  Google Scholar 

  96. Blohme I and Johansson S (1981) Renal pelvic neoplasms and atypical urothelium in patients with end-stage analgesic nephropathy. Kidney Int 20: 671–675

    Article  CAS  PubMed  Google Scholar 

  97. McCredie M et al. (1986) Phenacetin and papillary necrosis: independent risk factors for renal pelvic cancer. Kidney Int 30: 81–84

    Article  CAS  PubMed  Google Scholar 

  98. Busauschina A et al. (2004) Cyclosporine nephrotoxicity. Transplant Proc 36: 229S–233S

    Article  CAS  PubMed  Google Scholar 

  99. Markowitz GS et al. (2000) Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol 11: 1439–1448

    CAS  PubMed  Google Scholar 

  100. Rojek A et al. (2005) Altered expression of selected genes in kidney of rats with lithium-induced NDI. Am J Physiol Renal Physiol 288: F1276–1289

    Article  CAS  PubMed  Google Scholar 

  101. Cutting HO (1971) Inappropriate secretion of antidiuretic hormone secondary to vincristine therapy. Am J Med 51: 269–271

    Article  CAS  PubMed  Google Scholar 

  102. Steele TH et al. (1973) Antidiuretic response to cyclophosphamide in man. J Pharmacol Exp Ther 185: 245–253

    CAS  PubMed  Google Scholar 

  103. Edwards OM et al. (1970) Azotaemia aggravated by tetracycline. Br Med J 1: 26–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to sincerely thank the Dallas Veterans Affairs Hospital Library and Medical Media Section for their prompt responses in obtaining pertinent papers and creating the tables presented in this article.

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  1. University of Texas Southwestern Medical Center, and Director of Dialysis at the Veterans Affairs North Texas Health Care System, Dallas, TX

    Devasmita Choudhury

  2. Dialysis Unit at Drexel University College of Medicine, Philadelphia, PA, USA

    Ziauddin Ahmed

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Correspondence to Devasmita Choudhury.

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Choudhury, D., Ahmed, Z. Drug-associated renal dysfunction and injury. Nat Rev Nephrol 2, 80–91 (2006). https://doi.org/10.1038/ncpneph0076

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