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Reduced Renal Blood Flow (dehydration, CHF, ascites, renal artery stenosis, hypotension, hemorrhage, etc.)
Nephrotoxic agents (vanc, diuretics, cisplatin, lithium, methotrexate, allopurinol, PPIs)
Pre-existing renal disease
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ACEi/ARB
Pre-renal vasodilation of efferent arteriole
Presents as 30%+ inc. in SCr w/in 1-2 wks
- Minimize reduction of blood volume
- Use lowest dose of ACEi/ARB
- Monitor SCr + K
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NSAID/COX-2 MOI
Pre-renal vasoconstriction of afferent arteriole
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NSAID/COX-2 Presentation
- Inc. SCr, BUN, K & BP
- Dec. UO
- Edema
- Weight gain
- Granular casts
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NSAID/COX-2 RF
RFs: Age > 60 & SLE
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NSAID/COX-2 Prevention
Use alt. analgesia in high risk ptsAvoid potent NSAIDs (indomethacin)Avoid agents that reduce renal blood flow
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Cyclosporine & Tacrolimus MOI
Pre-renal
- ACUTE (< 6 months)
- Inc. prod. of vasoconstrictors
- Dec. prod. of vasodilators
- -> net dec. in filtration pressure
- CHRONIC (> 6 months)
- Inc. formation of extracellular matrices & endothelial cell damage
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Cyclosporine & Tacrolimus Presentation
- ACUTE (<6 months)
- Inc. SCr, HTN, hyperkalemia, Na retention
- Oliguria
- Injury dose dependent & reversible
- CHRONIC (>6months)
- Gradual SCr inc.
- Injuries usu. dose dependent and irreversible
- Biopsy: arteriolar hyalinosis
- Biopsy: glomerular sclerosis
- Biopsy: tubulointerstitial fibrosis
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Cyclosporine & Tacrolimus RFs
- Age > 65
- High doses
- 3A4 inhibitors
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Cyclosporine & Tacrolimus Prevention
- Cyclosporine trough of 100-200 ng/mL
- Tacrolimus trough of 5-15 ng/mL
- Maintain hydration & renal blood flow
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Acute Tubular Necrosis (Definition)
- Toxicity to renal tubular cells from direct drug
- exposure or ischemia from pre-renal injuries. Most common with aminoglycosides.
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ATN MOI
Cationic charges facilitate drug uptake -> generation of reactive O2 spp. -> cell necrosis
Degree of toxicity determined by # of cationic groups -> neomycin > tobra, gent, amikacin > strepto
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ATN Presentation
- S/Sx w/in 5-10d
- Gradual SCr & BUN inc.
- Nonoliguria
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ATN RFs
- Cumulative doses
- High troughs
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ATN Prevention
- Use alt. Abx
- Hydration
- QD dosing (lower troughs)
- Amikacin trough <10 mcg/mL
- Gent/Tobra trough <2-3 mcg/mL (1mcg if QD)
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Contrast media-induced Nephrotoxicity MOI
Accum. in tubules -> free radicals
Dec. perfusion -> release of vasoconstrictors, osmotic diuresis & inc. blood viscosity
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CIN Presentation
- S/Sx in 24-72h
- SCr peak in 3-5d
- Nonoliguria
- U/A -> hyaline or granular casts
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CIN RFs
- GFR < 60
- High dose contrast media
- High osmolarity contrast media
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CIN Prevention
Alt. imaging method
NS pre & post procedure w/bicarb (inc. pH = dec. free radicals)
Low volume, low osmolarity contrasts
NAC Tx (contraversial)
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Ampho B MOI
Binds to tubular cell membranes
Inc. cell permeability to loss of Na & K
Inc. O2 requirements
Dec. renal blood flow d/t vasoconstrictor release
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Ampho B Presentation
- 1-2 wks after initiation
- Inc. SCr& BUN
- Inc. excretion og Mg, K & Na
- Nonoliguria
- Distal renal tubular acidosis
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Ampho B RFs
- Cumulative dose
- Short infusion time
- Volume depletion
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Ampho B Prevention
- Alt. antifungal
- Limit dose
- Inc. infusion time
- Hydration
- Lipid-based formulations
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Acute Allergic Interstitial Nephritis
Immune-mediated damage to renal tubule cells or the interstitium
Implicated Agents: *Beta-lactams*, *NSAIDs*, AGs, vanc, sulfonamides, TCNs, rifampin, Ampho B, diuretics, COX-2s, PPIs, allopurinol, APAP, ASA...
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Beta-lactam & NSAID AAIN MOI
Antibodies to drug-hapten complexes or T-cell toxicitiy
Interstitial infiltration on leukocytes
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Beta-lactam AAIN Presentation
S/Sx ~14d after initiation
- Fever
- Maculopapular rash
- Eosinophilia
- Arthralgia
- Oliguria
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NSAID AAIN Presentation
S/Sx ~6 months after initiation
Less likely to have hypersensitivity symptoms
Proteinuria > 3.5 g/day in 70% of pts
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AAIN RFs
Idiosyncratic (none known)
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AAIN Prevention
None recommended d/t idiosyncratic nature
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Crystal Nephropathy Contributing Factors
- Urine pH
- Drug solubility/conc.
- Renal blood flow
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Acyclovir MOI
High urine conc. & relative insolubility -> precipitation
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Acyclovir Presentation
24-48hrs post initiation
- Crystaluria
- Pyuria
- Hematuria
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Acyclovir RFs
- Aggressive high-dose Tx
- Low volume states
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Acyclovir Prevention
- Dose reductions (based on renal fxn)
- Hydration
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DIRD general Tx Strategies
- D/C offending agent
- Dose reduction
- Supportive care (electrolytes and fluids)
- RRT in severe cases
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