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Appendix 6

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TABLE A6–1: Drug-Induced Kidney Structural–Functional Alterations
Tubular epithelial cell damage

Acute tubular necrosis

  • Aminoglycoside antibiotics

  • Radiographic contrast media

  • Cisplatin, carboplatin

  • Amphotericin B

  • Cyclosporine, tacrolimus

  • Adefovir, cidofovir, tenofovir

  • Pentamidine

  • Foscarnet

  • Zoledronate

Osmotic nephrosis

  • Mannitol

  • Dextran

  • IV immunoglobulin

Hemodynamically mediated kidney injury
  • Angiotensin-converting enzyme inhibitors

  • Angiotensin II receptor blockers

  • Nonsteroidal anti-inflammatory drugs (NSAIDs)

  • Cyclosporine, tacrolimus

  • OKT3

Obstructive nephropathy

Crystal nephropathy

  • Acyclovir

  • Sulfonamides

  • Indinavir

  • Foscarnet

  • Methotrexate

Nephrolithiasis

  • Sulfonamides

  • Triamterene

  • Indinavir

Nephrocalcinosis

  • Oral sodium phosphate solution

Glomerular disease

Minimal change disease

  • NSAIDs, COX-2 inhibitors

  • Lithium

  • Pamidronate

  • Interferon-α and -β

Membranous disease

  • NSAIDs

  • Penicillamine

  • Captopril

Focal Segmental Glomerulosclerosis

  • Pamidronate

  • Interferon-α and -β

  • Lithium

  • Sirolimus

  • Anabolic steroids

Tubulointerstitial disease

Acute allergic interstitial nephritis

  • Penicillins

  • Ciprofloxacin

  • NSAIDs, cyclooxygenase-2 inhibitors

  • Proton pump inhibitors

  • Loop diuretics

Chronic interstitial nephritis

  • Cyclosporine

  • Lithium

  • Aristolochic acid

Papillary necrosis

  • NSAIDs, combined phenacetin, aspirin, and caffeine analgesics

Renal vasculitis, thrombosis, and cholesterol emboli

Vasculitis and thrombosis

  • Hydralazine

  • Propylthiouracil

  • Allopurinol

  • Penicillamine

  • Gemcitabine

  • Mitomycin C

  • Methamphetamines

  • Cyclosporine, tacrolimus

  • Adalimumab

  • Bevacizumab

Cholesterol emboli

  • Warfarin

  • Thrombolytic agents

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TABLE A6–2: Potential Risk Factors for Aminoglycoside Nephrotoxicity

(A) Related to aminoglycoside dosing:

Large total cumulative dose

Prolonged therapy

Trough concentration exceeding 2 mg/La

Recent previous aminoglycoside therapy

(B) Related to synergistic nephrotoxicity. Aminoglycosides in combination with

Cyclosporine

Amphotericin B

Vancomycin

Diuretics

Iodinated radiographic contrast agents

Cisplatin

NSAIDs

(C) Related to predisposing conditions in the patient

Preexisting kidney disease

Diabetes

Increased age

Poor nutrition

Shock

Gram-negative bacteremia

Liver disease

Hypoalbuminemia

Obstructive jaundice

Dehydration

Hypotension

Potassium or magnesium deficiencies

a

The equivalent concentration in SI molar units are 4.3 μmol/L for tobramycin and 4.2 μmol/L for gentamicin.

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TABLE A6–3: Recommended Interventions for Prevention of Contrast Nephrotoxicity
Intervention Recommendation Recommendation Gradea
Contrast
  • Minimize contrast volume/dose

  • Use noniodinated contrast studies

  • Use low- or iso-osmolar contrast agents

A-1

A-2

A-2

Medications
  • Avoid concurrent use of potentially nephrotoxic drugs, eg, NSAIDs, aminoglycosides

A-2
Isotonic sodium chloride (0.9%)
  • Initiate infusion 3–12 hours prior to contrast exposure and continue 6–24 hours postexposure

  • Infuse at 1–1.5 mL/kg/h adjusting postexposure as needed to maintain a urine flow rate of 150 mL/h

  • Alternatively, in urgent cases, initiate infusion at 3 mL/kg/h, beginning 1 hour prior to contrast exposure, then continue at 1 mL/kg/h for 6 hours postexposure

A-1
N-acetylcysteine
  • Administer 600–1200 mg by mouth (PO) every 12 hours, 4 doses beginning prior to contrast exposure (ie, 1 dose prior to exposure and 3 doses postexposure)

B-1
a

Strength of recommendations: A, B, and C are good, moderate, and poor evidence to support recommendation, respectively. Quality of evidence: 1, evidence from more than 1 properly randomized, controlled trial; 2, evidence from more than 1 well-designed clinical trial with randomization, from cohort or case-controlled analytic studies or multiple time series, or dramatic results from uncontrolled experiments; 3, evidence from opinions of respected authorities, based on clinical ...

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