Therapeutics: DIN 1
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Where is the most common area for drug induced kidney injury?
What drugs damage the Tubules?
- Radiologic contrast media
- Cisplatin (Platinol) and Carboplatin (Paraplatin)
- Amphotericin B (Fungizone)
What are the AGs that cause DIN and in what order are they nephrotoxic to the tubules?
Neomycin > gentamicin & tobramycin > amikacin > streptomycin & netilmicin
What is the MOA of aminoglycoside induced DIN?
- Proximal tubule epithelial damage
- Leads to obstruction of tubular lumen and back-leakage of glomerular filtrate
What presentation is characteristic of aminoglycoside induced DIN?
- Gradual increase in SCr and decrease in CrCl after 6-10 days of therapy
- Non-oliguric decreases in K and Mg may also occur
What are the predisposing factors for Aminoglycoside induced nephrotoxicity?
- Pre-existing renal insufficiency
- Increased age
- G- bacteremia
- Liver disease
- Obstructive jaundice
- Poor nutrition
- K or Mg deficiencies
What other drugs should you not administer concomitantly with Aminoglycosides due to risk of nephrotoxicity?
- Amphotericin B
- Contrast Dye
What dosing recommendations should be made to avoid aminoglycoside nephrotoxicity?
- Trough should not be > 2mg/L
- Watch large doses and prolonged therapy
What non-dosing practices can you use to prevent aminoglycoside nephrotoxicity?
- Maintain Hydration and hemodynamic stability
- D/C other nephrotoxic agents
- Caution use of QD dosing
- D/C if SCr is > 0.5 mg/dL
- Limit time on therapy and dose size
What are the 1st generation Iodinated contrast dyes?
- Ioxaglate (Hexabrix)
- Iothalamate (Conray)
- Diatrizoate (Cystografin)
What are the 2nd generation Iodinated contrast dyes?
- Iohexol (Omnipaque)
- Ioversol (Optiray)
- Iopamidol (Isovue)
Are 1st generation contrasts dyes considered ionic or non-ionic?
Are 2nd generation contrasts dyes considered ionic or non-ionic?
Are 1st generation contrasts dyes considered hyperosmolar or low osmolar?
Are 2nd generation contrasts dyes considered hyperosmolar or low osmolar?
What are the risk factors for Contrast nduced nephrotoxicity?
- Renal insufficiency (SCr >1.5, eGFR < 60)
- CV disease (HF, MI)
- Age >70
- Large volume contrast
- Multiple contrast examinations within a short time interval
Metformin with Contrast dye can cause what adverse reaction?
When should you start stop Metformin when contrast dye is going to be used?
- Stop: at time or before or procedure
- Start: 48 hours after procedure and after evaluation of kidney function
What is the MOA of Cisplatin and Carboplatin in DIN?
- Binds cellular proteins and forms sulfhydryl groups
- Disrupts cell enzyme activity
- Uncouples oxidative phosphorylation
- Creates reactive O2 intermediates
What are the risk factors for developing DIN from Carboplatin and Cisplatin?
- Increased age
- Alcohol abuse
- Renal irradiation
What type of damage occurs due to Cisplatin and Carboplatin?
Proximal tubule damage
What is the clinical presentation for Cisplatin or Carboplatin DIN?
- SCr peaks 10-12 days after therapy
- Should go down after 21 days
- Can cause irreversible chronic renal failure
- Damage is cumulative from treatments
- Low K, Ca, Mg
What is Amfostine used for?
Pretreatment for Cisplatin and Carboplatin to reduce myelosupression, ototoxicities, Neuro and nephro-toxicities
What is the dose for Amifostine for Carboplatin, Cisplatin pretreatment?
- 910 mg/m^2
- Give 30 minutes before cisplatin
Describe the MOA of Amfostine:
- Organic thiophosphate
- Chelates platins
Is Cisplatin/Carboplatin therapy reversible
- May be
- Cumulative toxicity may not be
What is the MOA of Amphotericin B in DIN?
- Direct tubular epithelial damage
- Increase tubular permeability and necrosis
- Arterial vasoconstriction
- Ischemic damage
What is the clinical presentation of Amphotericin B caused DIN?
- Increased SCr and BUN
- Decreased K, Na and Mg
- Impaired urine concentrating abilities
What are the risk factors for Amphotericin B caused DIN?
- Baseline renal insufficiency
- High average daily dose, or rapid infusion
- Diuretics, volume depletion
- Concomitant nephrotoxic drugs (i.e. cyclosporine)
What are the liposomal amphotericin B formulations?
What ways can you prevent Amphotericin B DIN?
- Limit cumulative dose
- Avoid concomitant nephrotoxins
- Hydrate w/ 1 IV NS or high Na diet
- Use liposomal formulations
What can cause Tubular epithelial damage through osmotic nephrosis?
- LMW Dextran
- Radio contrast dye
- Propylene glycol
- Immune globulin
What are the mechanisms of osmotic nephrosis?
- Form vacuoles and causes swelling
- Leads to necrosis and proximal tubular epithelial damage
Osmotic dieresis/volume depletion can increase nephrotoxicity of what drugs?
How can you prevent osmotic nephrosis?
- Limit dose of offending agent
- Avoid dehydration
- Watch concomitant diuretics
What drugs can cause hemodynamically medicated AKI?
- Cyclospirne (CSA) or Tacrolimus
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