Nephrology Book

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Nephrotoxic Drugs

Aka: Nephrotoxic Drugs, Drug-induced Nephrotoxicity
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  1. See Also
    1. Acute Tubulointerstitial Nephritis for drug causes
    2. Nephrotoxicity due to NSAIDs
  2. 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
  3. 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
  4. 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
  5. Causes: Chemotherapy and Immunosuppressants
    1. Cisplatin
    2. Methotrexate
    3. Mitomycin
    4. Cyclosporine
    5. Ifosphamide (Causes Fanconi's Syndrome)
    6. Zoledronic Acid (Zometa)
  6. Causes: Heavy Metals
    1. Mercury Poisoning
    2. Lead Poisoning
    3. ArsenicPoisoning
    4. Bismuth
    5. Lithium related Kidney disorders
      1. Polydipsia and Nephrogenic Diabetes Insipidus
      2. Acute Renal Failure
        1. Dialysis indications: Creatinine >2.5 or Seizures, ALOC, Rhabdomyolysis
      3. Chronic Kidney Disease with fibrosis
  7. Causes: AntiHyperlipidemics
    1. Statin Drugs (Rhabdomyolysis)
    2. Gemfibrozil
      1. Associated with Acute Renal Failure due to Rhabdomyolysis
  8. 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
    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
  9. Causes: Drugs of abuse
    1. Cocaine
    2. Heroin
    3. Methamphetamine
    4. Methadone
  10. Causes: Reversible Serum Creatinine increase without significant effect on GFR
    1. Cimetidine
    2. Fenofibrate (Tricor)
    3. Trimethoprim
  11. References
    1. Naughton (2008) Am Fam Physician 78(6): 743-50
    2. Thatte (1996) Postgrad Med 100(6):83-100

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