DIKD Flashcards
What are the 3 most common manifestations of drug induced kidney disease? (DIKD)
- Decline in GFR
- Rise in serum creatinine (Scr)
- Rise in BUN (blood urea nitrogen)
BUN is a marker of reanl health. If GFR and blood volume are decreased, will BUN be elevated or decreased?
Increased
How is nephrotoxicity reversible?
Offending agent discontinued
6 things to look out for in DIKD
“HE A PUP”
- Hematuria
- Electrolyte imalances
- Acid-base abnormalities
- Proteinuria
- Urine sediment abnormalities
- Pyuria-neutrophils (pus) in urine
Blood flows through the ___ arteriole, to the glomerulus, and exits through the __ arteriole.
- afferent (arrives)
- efferent (exits)
A decrease in blood flow and renal perfusion can lead to _____.
a pre-renal reduction in renal function
Under conditions in which renal blood flow is diminished, the kidney maintains glomerular ultrafiltration by _____ the _____ arterioles and _____ the _____ arterioles.
- vasodilating the afferent
- vasoconstricting the efferent
Damage to the glomerular or tubular regions can lead to…
intrinsic AKI
Obstruction of urine flow in the collecting tubule, ureter, bladder, or urethra is termed _____
post-renal impairment
3 parameters to assess for possible drug-induced AKI
- Abrupt (48 hrs) reduction in kidney function defined as absolute increase in Scr of greater than or equal to 0.3mg/dL
- Percentage increase in Scr of greater than or equal to 50% (1.5 fold from baseline) within 7 days
- Reduction in urine output (documented oliguria of less than 0.5 mL/kg/h for more than 6 hrs), when correlated temporally w/ the initiation od drug
3 causes of pre-renal AKI
-
Transient renal hypoperfusion:
- Hypotension
- Decreased CO
- Decreased effective arterial blood volume
1 cause of Post-renal AKI
Obstruction of urinary tract
3 causes of Intrinsic AKI
- Acute glomerulonephritis (inflammation/damage to glomerular membrane)
- Acute interstitial nephritis (allergic rxn may be caused by drugs)
-
Acute tubular necrosis (accounts for more than 50% of cases of AKI)
- nephrotoxic agents
- prolonged renal hypoperfusion
Causes of what?
- drug-induced osmotic diuresis
- Diabetes Insipidus
- burns
- 3rd space losses (hypoalbuminemia)
Volume Depletion leading to Pre-renal AKI
3 drugs which cause Pre-Renal AKI
- NSAIDS
- ACE-I
- ARBs
Cause of what?
- Exogenous Toxins (nephrotoxic drugs, contrast dyes)
Acute Tubular Necrosis
Causes of what?
- NSAIDS and certain abx
Acute Interstitial Nephritis
Causes of what?
- BPH
- Malignancy
- Anticholinergic drugs
- Displaced bladder catheter
Bladder outlet obstruction –> Post-renal AKI
____ is the most common presentation of DIKD in hospitalized patients
Acute Tubular Necrosis (ATN)
What are the 6 primary agents causing ATN –> DIKD in hospitalized pts?
RAACO
- Radiocontrast media**
- Aminoglycoside abx**
- Amphotericin B**
- Cisplatin
- Osmotically active agents
Pathogenesis is a decrease in glomerular capillary hydrostatic pressure
- ACI-I
- NSAIDS
Hemodynamically mediated kidney injury
- 27% of kidney biopsies performed for hospitalized pts w/ unexplained AKI
-
Clinical manifestations present approximately 14 days after initiation of therapy:
- fever, maculopapular rash, eosinophilia
- arthralgia, pyuria, hematuria
- proteinuria, oliguria
Acute Allergic Interstitial Nephritis (AAIN)
Which 2 drugs cause the majority of allergic rxns?
- PCN
- Sulfa
Pharmacokinetic Alterations
- What can significantly increase the volume of distribution of many drugs
- What is often an accompanying problem resulting in: -reduction in CO -reduction in liver function
- Edema
- Multisystem organ failure
What 3 medications are affected by Pharmacokinetic Alterations?
- Vancomycin (tx MRSA and gram +)
- Aminoglycosides
- Low-molecular-weight heparins
Electrolyte Disorders
- Most common electrolyte disorder
- >__% of ___ is renally eliminated
- Life-threatening cardiac arrhythmias
- Frequent monitoring needed
Hyperkalemia
Which 2 elements are both eliminated by the kidneys and are not removed efficiently by dialysis?
Phosphorus & Magnesium
What 3 drugs can cause hyperkalemia?
We don’t “recycle” potassium. But we can prevent the excretion. It is NOT well regulated by the kidneys.
- ACE
- ARB
- K-sparing (spirinolactone)
Amphotericin is a terrible drug which kills what?
Fungi
Types of what?
- Acute Tubular Necrosis
- Osmotic nephrosis
Tubular Epithelial Cell Damage
Types of what?
- Intratubular obstruction
- Nephrolithiasis
- Nephrocalcinosis
Obstructive nephropathy
Types of what?
- Acute allergic interstitial nephritis
- Chronic interstitial nephritis
- Papillary necrosis
Tubulointerstitial disease
3 agents causing osmotic nephrosis (Tubular Epithelial Damage)
- Dextran
- IV immunoglobulin
- Mannitol
Pathogenesis of what?
- Accumulation of high drug concentrations within proximal tubular epithelial cells
- Produces reactive oxygen species causing mitochondrial injury
- LEADS TO KIDNEY NECROSIS**
- Toxicity is related to the # of cationic groups on the molecule
- Neomycin>Gentamicin>Tobramycin>Amkacin
Aminoglycoside (AG) Nephrotoxicity
Clinical presentation of what?
- Nonoliguria
- Evidence of injury seen within 5-10 days after initiation of therapy*** (not abrupt)
- Gradual progressive rise in Scr and BUN and decrease in CrCl
- Full recovery of renal function is common if therapy is immediately discontinuted
Aminoglycoside Nephrotoxicity
If an aminoglycoside must be used, which one should be used?
Amikacin
3 risk factors of Aminoglycoside Nephrotoxicity
-
Aggressiveness of AG dosing
- large cumulative dose
- prolonged therapy
- Synergistic toxicity w/ other nephrotoxins
-
Preexisting clinical conditions
- CKD
- DM
- Older age
- Dehydration
How do you prevent Aminoglycoside Nephrotoxicity?
- Avoid volume depletion**
- Use alternative abx when possible
- Limit total dose administered
- Avoid concomitant nephrotoxic drugs
4 ways to manage Aminoglycosde Nephrotoxicity
- Discontinue AG or revise dosing regimen
- Stop other nephrotoxic drugs
- Adequate hydration
- Renal Replacement Therapy (RRT)
DARS
Pathogenesis of what?
- Renal ischemia from systemic hypotension and acute vasoconstriction**
- Disruption of normal renal blood flow may last for several hours
- Increased contrast in renal tubules, exacerbating direct toxicity
- extent of cellular toxicity directly related to contrast exposure
Contrast-Induced Nephrotoxicity (CIN)
Presentation of what?
- Nonoliguria (>500ml urine/ day)
- Injury present within first 24-48 hrs after administration*
- Scr usually peaks between 3 and 5 days after exposure*
- Recovery after 7 - 10 days*
Contrast Induced Nephrotoxicity (CIN)
What are the 3 main risk factors of Contrast-Induced Nephrotoxicity (CIN)?
- Pre-existing kidney disease* (GFR<60)
- Decreased renal blood flow* (CHF, dehydration/volume depletion, hypotension, diabetes)
- Concurrent use of nephrotoxins* (NSAIDs, ACEIs)
(as # of risk factors increase, mortality increases)
4 ways to prevent Contrast Induced Nephrotoxicity (CIN)
- Use alternative imaging procedures*
- Hydration
- Antioxidants (ascorbic acid, N-acetylcysteine)
- Hemofiltration
Management of Contrast Induced Nephrotoxicity (CIN)
- Supportive Care
- Monitoring (renal function, electrolytes, volume status)
- RRT when indicated (renal replacement therapy)
