II. Risk Factors: Nephrotoxicity

  1. See Nephrotoxicity Risk
  2. Concurrent medications that interfere with GFR autoregulation or renal blood supply
    1. Angiotensin-converting enzyme inhibitors (ACE Inhibitors)
    2. Angiotensin Receptor Blockers (ARBs)
    3. Cycosporine
    4. Non-Steroidal Antiinflammatory drugs (NSAIDs)
    5. Tacrolimus

III. Evaluation: Criteria to consider stopping agent due to nephrotoxicity

  1. Relative Serum Creatinine increase 50% over baseline
  2. Absolute Serum Creatinine increase
    1. Serum Creatinine baseline <2 mg/dl: Creatinine increase 0.5 mg/dl over baseline
    2. Serum Creatinine baseline >2 mg/dl: Creatinine increase 1.0 mg/dl over baseline

IV. Causes: Medication mediated injury by renal site

  1. Prerenal Failure Causes (primarily intra-renal Vasoconstriction)
    1. See Acute Prerenal Failure
    2. Duretics (volume depletion)
    3. Tacrolimus
    4. Cyclosporine
    5. NSAIDs inhibit cyclooxygenase
      1. Depletes renal vasodilatory eicosanoids
      2. Exacerbates Vasoconstriction afferent arterioles
        1. Volume depletion
        2. Elderly
        3. Edema
    6. ACE Inhibitors (and ARBs) lower renal perfusion
      1. Result in dilated efferent arterioles
      2. Decrease Glomerular Filtration Rate
  2. Intrinsic Renal Failure - Interstitial causes (onset 2 weeks after medication started)
    1. See Acute Interstitial Nephritis
    2. Penicillins and Cephalosporins
      1. Hypersensitivity (fever, rash, Arthralgia)
    3. Sulfonamides
      1. Vasculitis reaction
    4. NSAIDs
      1. Nephrotic Syndrome type reaction
    5. Acyclovir (Zovirax)
    6. Rifampin
    7. Diuretics (Thiazides and Lasix)
    8. Allopurinol
    9. Cimetidine
    10. Ciprofloxacin
    11. Phenytoin (Dilantin)
    12. Interferon
    13. Proton Pump Inhibitors (e.g. Omeprazole)
    14. Other medications have caused AIN to a lesser extent
  3. Intrinsic Renal Failure - Tubular Injury causes (Acute Tubular Necrosis causes)
    1. Intravenous Contrast Related Acute Renal Failure
    2. Aminoglycosides
    3. Cisplatin
    4. Methotrexate
    5. Ethylene Glycol
    6. Amphotericin B
  4. Intrinsic Renal Failure - Glomerular injury
    1. See Glomerulonephritis Causes (especially RPGN)
    2. Penicillamine
    3. Hydralazine
    4. Allopurinol
    5. Rifampin
  5. Postrenal causes (intrarenal obstruction at distal tubules)
    1. Uric Acid crystals (Hyperuricemia, Gout)
      1. Methotrexate
      2. Acyclovir
      3. Protease Inhibitors (e.g. Indinavir or Crixivan)

V. Causes: Antibiotics

  1. Aminoglycosides (10-15% Incidence of Acute Tubular Necrosis)
    1. Occurs in 10-20% patients on 7 day course
    2. Results in non-oliguric increased Creatinine
    3. A single dose early in septic course is usually safe
  2. Sulfonamides
  3. Amphotericin B
    1. Incidence 80-90%, esp. with deoxycholic acid formulation
    2. Causes Acute Tubular Necrosis
  4. Foscarnet
  5. Quinolones (e.g. Ciprofloxacin, Levofloxacin)
  6. Rifampin
  7. Tetracycline
  8. Acyclovir (only nephrotoxic in intravenous form)
    1. Causes Acute Interstitial Nephritis and crystal nephropathy
  9. Pentamidine
  10. Vancomycin

VI. Causes: Chemotherapy and Immunosuppressants

  1. Cisplatin
  2. Methotrexate
  3. Mitomycin
  4. Cyclosporine
  5. Ifosphamide (Causes Fanconi's Syndrome)
  6. Zoledronic Acid (Zometa)

VII. Causes: Heavy Metals

VIII. Causes: AntiHyperlipidemics

IX. Causes: Miscellaneous Drugs

  1. Chronic Stimulant Laxative use
    1. Resulting chronic volume depletion and Hypokalemia causes nephropathy
  2. Radiographic contrast
    1. See Intravenous Contrast Related Acute Renal Failure
  3. ACE Inhibitors
    1. Expect an increase of Serum Creatinine in Chronic Kidney Disease
    2. See ACE Inhibitors for guidelines on Serum Creatinine rise that warrants stopping medication
  4. NSAIDs
      1. See Nephrotoxicity due to NSAIDs
  5. Aspirin
    1. Low dose Aspirin reduces Renal Function in elderly
      1. Decreased Creatinine Clearance after 2 weeks of use
      2. Changes persisted for at least 3 weeks off Aspirin
      3. Segal (2003) Am J Med 115:462-6 [PubMed]
  6. Mesalamine (Asacol, Pentasa)
    1. Mesalamine is an NSAID analog and has systemic absorption from the bowel
    2. See Nephrotoxicity due to NSAIDs
  7. Chinese Herbals containing aristocholic acid

X. Causes: Drugs of Abuse

XI. Causes: Reversible Serum Creatinine increase without significant effect on GFR

  1. Cimetidine
  2. Fenofibrate (Tricor)
  3. Trimethoprim

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Related Studies (from Trip Database) Open in New Window

Ontology: Toxic nephropathy (C0595916)

Concepts Disease or Syndrome (T047)
SnomedCT 236514003, 27893002
English NEPHROPATHY TOXIC, Nephropathy toxic, Toxicity renal, renal toxicity, toxic nephropathy (diagnosis), toxic nephropathy, nephropathy toxic, Toxic nephrosis, Toxic nephropathy, Toxic nephropathy (disorder), nephropathy; toxic, toxic; nephropathy, Toxic nephropathy, NOS
Italian Nefropatia tossica, Tossicità renale
Dutch renale toxiciteit, nefropathie; toxisch, toxisch; nefropathie, toxische nefropathie
French Toxicité rénale, NEPHROPATHIE TOXIQUE, Néphropathie toxique
German Nierentoxizitaet, toxische Nephropathie, NEPHROPATHIE TOXISCH, Nephropathie toxisch
Portuguese Toxicidade renal, NEFROPATIA TOXICA, Nefropatia tóxica
Spanish Toxicidad renal, NEFROPATIA TOXICA, nefropatía tóxica (trastorno), nefropatía tóxica, nefrosis tóxica, Nefropatía tóxica
Japanese 中毒性ネフロパシー, チュウドクセイネフロパシー, 腎毒性, ジンドクセイ
Czech Toxická nefropatie, Renální toxicita
Hungarian Toxikus nephropathia, Vesetoxicitás

Ontology: renal toxin (C0597372)

Concepts Hazardous or Poisonous Substance (T131)
English renal toxin

Ontology: Drug-induced renal disease (C3671895)

Concepts Finding (T033)
SnomedCT 282631000009106
English Drug-induced renal disease, Drug-induced nephrotoxicosis, Drug-induced renal disease (disorder)