21 - Drug Induced Renal Disease Flashcards
How to ID
Drug-Induced AKI
Generally detected by routine daily labs, but:
SCr can LAG behind renal dmg by 1-2 days
Due to delay / not taking labs (outpatient setting) we check symptoms:
Decreased Urination
HYPERvolemia = EDEMA
Nausea / loss of appetite / Malaise
Confusion
Prevention of Drug-Induced AKI
_AVOID using nephrotoxic drug_s
in patients with these risk factors for AKI:
Already Existing:
Renal Insufficiency / Nephrotoxic Meds
IVF depletion
Dehydrated / HF / Cirrhosis / Loop Diurtics
ELDERLY
What causes:
PSEUDO-DRUG-induced Renal Disease?
Most commonly:
- *TRIMETHOPRIM** (from bactrim)
- also* Dronaderone (new drug)
↑SCr due to competitive inhibition of Creatinine secretion
within the proximal tubule
↑SCr by as much as 0.5 mg/dL
without changing GFR
- *Causes of** PRE-RENAL
- *Drug-Induced Renal Disease**
Drugs and Mechanism
- *Pre-Renal AKI** is due to a
- reduction in renal blood flow*
Loop Diuretics
ACE-I + ARBs
NSAIDs
Cyclosporine & Tacrolimus
- *Types of** INTRINSIC
- *Drug-Induced Renal Disease**
Glomerular Disease
Drug-Induced AutoImmune -
NSAID / Lithium / Quinolones / BisPhos
ATN = Acute Tubular Necrosis
AminoGlycosides / Contrast / CisPlatin-CarboPlatin / Amphotericin B
Intratubular Obstruction
Precipitation of Drug Crystals @ distal tubule
Acyclovir / Foscarnet / Methotrexate
Statin Induced Rhabdo (CSA + Statin)
AIN = Acute Interstitial Nephritis
Methicillin (most common) PPIs, ultimately ANY DRUG
not dose dependent, drug-induced ALLERGIC rxn
Loop Diuretic Induced AKI
What Type of AKI?
PRE-RENAL
- *Too HIGH DOSE**
- -> decreased IVF –> decreased Renal Blood Flow / filtration
- *Increased SCr & AKI**
In HF or Cirrhosis, often have to choose between:
Relieving Edema/Ascites
OR
causing AKI / Hypotension
Inadvertant cause of
PRE-RENAL AKI
PRE-RENAL AKI
HCTZ
is used for HT in a patient that then gets EDEMA
VVV
Add LOOP DIURETIC, w/o holding HCTZ
VVV
PROFOUND DIURESIS
ACE + ARB Induced AKI
What Type of AKI?
PRE-RENAL AKI
ACE/ARB –BLOCK-> RAAS
VVV
E-fferent renal VasoDILATION
usually effects in NO or small increase in Scr
- *Effect is GREATER if patient has** RENAL ARTERY STENOSIS
- *RAAS used to COMPENSATE**
typically OKAY due to second kidney
BUT, Contraindicated in BILATERAL Stenosis
- *Renal Artery Stenosis + ACE/ARBS**
- *AKI**
Stenosis of A-ferrent Arterioles
VVV
Reduction in Blood flow TO KIDNEYS
less Arteriolar pressure
VVV
INCREASED RAAS system to COMPENSATE
(E-ferrent VasoCONSTRICTION, normally)
- BUT:*
- *ACE/ARBs are BLOCKING the COMPENSATION SYSTEM**
Normally would be able to compensate with SECOND KIDNEY, but in Bilateral Renal Artery Stenosis –> ACE/ARB are Contraindicated
NSAID Induced AKI
What Type of AKI?
- *PRE-RENAL AKI**
- can occur within days*
NSAIDs -block-> prostaglandin VasoDILATION
VVV
A-ferrent Arteriolar VasoConstriction
-> decreased IntraGLOMERULAR PRESSURE + FIltration
VVV
Increased SCr –> AKI
- *Even be WORSE with ACEI or ARB**
- *A-ferrent + E-ferrent Constriction**
What drugs cause
E-fferent VasoDILATION?
- *ACE-Inhibitors**
- prils
- *ARBs**
- sartans
What drugs cause
A-fferent VasoCONSTRICTION
NSAIDS
Pre-Renal, Induced AKI
CycloSporine A** + **TACrolimus
Pre-Renal, induced AKI –> chronic ischemia –> delayed chronic tubulointererstitial Nephritis
Amphotericin
- *Cyclosporine_ & _Tacrolmus**
- *Induced AKI**
PRE-RENAL AKI
irony for renal transplant patients
Cause Vasoconstriction of A-fferent Arterioles
Can result in Chronic Ischemia –> Delayed Chronic Tubulointerstitial Nephritis
- *DOSE RELATED**
- can reduce dose rather than DC*
- *Drug Induced Glomerular Disease**
- *INTRINSIC AKI**
- *Drug-Induced AUTOIMMUNE DISEASE**
- not a DIRECT cellular toxicity*
Causes: PROTEINURIA
NSAIDs / Lithium / Quonolones / Bisphosphonates
Management:
- *D/C Drug**
- *steroids** if renal fxn does not improve
What DRUGS cause
ATN
Drug-Induced Acute Tubular Necrosis
(INTRINSIC AKI)
Aminoglycosides
most common, insidiuous presentation, autodigestion of proximal tubules
- *Cisplatin + Carboplatin**
- hypomag*
Amphotericin B
A-fferent arterial vasoconstriction, hypomag
Radiographic Contrast Media
AminoGlycosides = AGs
Cause what type of AKI?
Drug-Induced ATN = Intrinsic AKI
Highest rates of drug-induced AKI
Risk factors:
High Trough Levels, want to keep < 1.0
Use with other nephrotoxic drugs
Kidney-Liver Disease / Age / HypoVolemia / Critically Ill
How do AGs cause AKI?
AGs are freely filtered through glomerulus
VV
Accumulates in LYSOSOMES of the PROXIMAL tubule
–> Lysosomes BURST
= Autodigestion of Proximal Tubules
VV
unable to CONCENTRATE URINE –> High Output AKI
Keep Trough Levels < 1
INSIDIOUS NEPHROTOXICITY
keep repeateing trough –> can SPIKE
AminoGlycoside Induced ATN
INTRINSIC AKI
TREATMENT / MANAGEMENT
- Discontinue AG*
- -> start ALTERNATIVE
START NS
to make sure the
associated HIGH URINE OUTPUT
does NOT exacerbate the AKI
by causing a PRE-RENAL AKI as well
IV Radiographic Contrast Media
Causes what type of AKI?
ATN** = **Intrinsic AKI
Unknown Mechanism:
- *renal vasoconstriction** –> medullary hypoxia
- *cytotoxic effects** –> directly on tubular cells
Clinical Features:
- ↑*SCrwithin24-48 hours after contrast
- NON-oliguric AKI* + FALSELY elevated PROTEINURIA
IV Radiographic Contrast Media
induced ATN - Intrinsic AKI
Risk Factors & Prevention
Prevention: Volume Expansion with NS
sodium bicarb / N-acetylceysteine is NO longer recommended
Risk Factors:
CKD w/ CrCl <60, especially if DM Nephropathy
HF / Hypovolemia / Hemodynamic instability
HIGH OSM / DOSE Contrast
Intra-arterial > intra venous
concurrant use of nephrotoxins
Cisplatin & Carboplatin
Causes what type of AKI?
Drug-Induced ATN = INTRINSIC AKI
Carboplatin = low risk of AKI
CISplatin = DOSE RELATED
HypoMAGNESEMIA = HALLMARK FINDING
Treated with:
IV Hydration –> maintain urine output 3-4 L/day
Amphotericin
Causes what type of AKI?
Drug-Induced ATN = INTRINSIC AKI
Ampho-terrible –> for fungal infections
Mechanism:
binds to ergo sterol in cell membranes of tubular cells –> necrosis of proximal tubile –> non-oliguric AKI
A-ferrent Ateriolar Vasoconstriction
Presentation:
HypoMagnesemia / HypoKalemia
Acidosis / Non-oliguric AKI
Amphotericin-Induced ATN
INTRINSIC AKI
PREVENTION & Risk Factors
Prevention:
Use LIPID FORMULATION
liposomal amphotericin B, reduces renal concentrations
Long infusion Time (4-6 hours) + PRE-INFUSION of 1L NS
Risk Factors:
HypoVolemia / HypoKalemia
Large doses / other nephrotoxins
Acyclovir / Foscarnet / Methotrexate / Statins
cause WHAT TYPE of AKI?
Intratubular Obstruction = INTRINSIC AKI
Precipitation of DRUG CRYSTALS –> DIstal Tubule
VV
can lead to obstruction of the tubule
as well as:
Interstitial nephritis due to autoimmune response or ATN
Risk Factors:
low Urine volume / low urinary pH (acidic)
How to treat
Methotrexate-induced
INTRATUBULAR OBSTRUCTION?
Intrinsic AKI
Methotrexate:
low urinary pH + HIGH doses
Premedicate w/ FLUIDS + BICARB –> Urine pH > 7
AKI can be
treated with GLUCARPIDASE
which metabolizes the methotrexate
Statin Induced Rhabdomyolysis
occurs more often with what other drug?
Clinical Presentation?
IntraTubular Obstruction = Intrinsic AKI
CYCLOSPORINE
with Atorvastatin –> 800-1000% increase in levels
Presentation:
MUSCLE PAIN + Weakness
RED-BROWN URINEdue tomyoglobunuria
Heme pigment –> obstruction of tubules -> AKI
Elevated Creatinine Kinase > 5x ULN (200)
Statin Induced Rhabdomyolysis
IntraTubular Obstruction = Intrinsic AKI
MANAGEMENT
Red-Brown Urine due to Myoglobinuria + 5xULN of CK
FLUID RESUSCITATION w/ NS
to improve renal perfusion
dilution of heme pigment / wash out obstruction casts
IV SODIUM BICARB
for alkalization –> prevents HEME-PROTEIN precipitation
maintain urine pH >6.5
lacks evidence for efficacy
Methicillin / PPIs
causes what type of AKI?
AIN = Acute Interstitial Nephritis
INTRINSIC AKI
- *AIN can be caused by ANY DRUG**
- just more commonly METHICILLIN + PPIs*
Drug-Induced ALLERGIC REACTION = not dose dependednt
can also be caused by:
Autoimmune disorders / Infections, but 75% drug-induced
Acute Interstitial Nephritis = AIN
Intrinsic AKI
Clinical Manifestations + Management
Management:
- *D/C THE DRUG,** if no improvement in SCr in 3-7 days
- -> CORTICOSTEROIDS = Prednisone 40-60mg QD
- until creatinine returns to baseline*, can be on therapy for 2-3 mo
Manifestation:
URINE WBC CASTS
Onset can be several weeks-months after stating drug
if previously exposed –> onset can be 1-3 days
Usually does NOT have significant PROTEINURIA
except with NSAID-induced AIN
allergic s/sx are typicaly NOT present
What drugs cause
DRUG-INDUCED KIDNEY STONES?
Obstructive Post-Renal AKI
TRIAMTERENE
Drug precipitation - 0.4%
SULFADIAZINE
poorly soluble –> crystaluria
30% incidense
