Kidney Disorders 4 Flashcards
DIKD, Dose adjustments
What is drug-induced kidney disease?
adverse structural or functional change to kidney after admin of a drug, chemical or biological product
How is the diagnosis of drug-induced kidney disease made?
changes in SCr or urine output are consistent with an AKI
kidney injury temporarily associated with use of a nephrotoxic drug
kidney injury due to a disease process is ruled out
True or false: drug-induced kidney disease is often irreversible
false
When discussing drug-induced kidney disease, which patient population are we generally referring to?
people who had an otherwise healthy kidney
-not someone with CKD
-still can and does happen to people with CKD
What is the presentation of drug-induced kidney disease?
metabolic acidosis
changes to serum electrolytes
proteinuria
pyuria
hematuria
rise in SCr (or reduced eGFR)
decreased (or increased) urine output
What are the symptoms of drug-induced kidney disease?
malaise
anorexia
N/V
volume overload (SOB or edema)
What are the mechanisms of drug-induced nephrotoxicity?
- indirect nephrotoxicity
-disruption of renal blood flow (pre-renal) - direct kidney injury/damage (intra-renal)
-acute tubular necrosis
-interstitial nephritis
-glomerulonephritis - obstructive uropathy (post-renal)
- others
What are examples of drugs that can cause pre-renal/hemodynamically mediated kidney injury?
ACEI/ARBs
NSAIDs
SGLT2 inhibitors
calcineurin inhibitors (tacrolimus, cyclosporine)
What is pre-renal drug induced kidney injury?
changes to blood flow
-acute decrease in GFR
How much of our resting CO do our kidneys receive?
25%
Which populations are at risk of pre-renal drug induced kidney injury?
HF
renal artery stenosis
volume depletion
CKD
How do we manage pre-renal drug induced kidney injury?
recognize + address other risk factors
“start low and go slow”
-monitor serum concentrations where applicable
monitor SCr, BUN, elytes
watch for concurrent diuretics, hypotensive agents
decrease dose or d/c therapy as appropriate
What is acute tubular necrosis?
ischemic or toxic cellular injury to renal tubules
-see casts in urine
generally dose-dependent
What is a preventative measure that should be taken with drugs that cause tubular necrosis?
maintaining adequate hydration
-“flush it out”
Which patients are at risk for acute tubular necrosis?
patients pre-disposed to renal injury
-CKD, old age, multiple nephrotoxic drugs
Which drugs can cause acute tubular necrosis?
aminoglycosides
calcineurin inhibitors
cisplatin
radiographic contrast media
amphotericin B
antivirals
zoledronate
What is the management of acute tubular necrosis?
discontinue nephrotoxin
hydration
monitor SCr, BUN, elytes
What is acute interstitial nephritis?
immune-mediated kidney injury associated with hypersensitivity reactions
-idiosyncratic
-inflammatory
-typically occurs 7-14 days after exposure
What do we find in the urine of a patient with acute interstitial nephritis?
pyuria
eosinophils
no bacteria
What are the symptoms of acute interstitial nephritis?
fever
rash
arthralgia
eosinophilia
What are some drugs that can cause acute interstitial nephritis?
penicillins/cephalosporins
NSAIDs
ciprofloxacin
PPIs
allopurinol
loop diuretics
phenytoin
What is the management of acute interstitial nephritis?
d/c nephrotoxin, provide corticosteroid (maybe)
monitor SCr, BUN, and symptoms
What is chronic interstitial nephritis?
progressive and irreversible
-ex: lithium, calcineurin inhibitors
What are some drugs that can cause obstructive nephropathy?
sulfonamides
acyclovir
methotrexate
oral phosphate solution
triamterene
ciprofloxacin
What is obstructive nephropathy?
blockage with:
-precipitated drug crystals (ex: acyclovir, triamterene, ciprofloxacin)
-tissue degradation products released by drug
-precipitated calcium phosphate (sodium phosphate solution) or calcium oxalate crystals (ascorbic acid)
What is the correlation between drug dose and obstructive nephropathy?
obstructive nephropathy is dose-dependent
What is obstructive nephropathy associated with?
inadequate hydration
-supersaturation and decreased urine pH
Why does medication use in renal impairment require consideration?
to prevent drug accumulation and associated adverse or toxic effects
What is the management of obstructive nephropathy?
high urine volume
urinary alkalinization
Which pharmacokinetic parameters are impacted by renal impairment?
absorption/bioavailability
distribution
metabolism
elimination
Changes to which pharmacokinetic parameters via renal impairment are considered to be clinically relevant?
distribution and elimination
-distribution impacted by edema, decreased protein binding, uremia and metabolic acidosis
-elimination impacted by decreased filtration and alterations in tubular secretion and reabsorption
Which equation do we use for renal dose adjustments?
Cockcroft-Gault
What are the potential problems with drug use in CKD?
reduced excretion of drugs and/or their metabolites
increased sensitivity to drugs
diminished tolerance to side effects
loss of efficacy
What are the general principles for drug dosing in renal impairment?
generally if CrCl > 60ml/min, empiric dose adjustments not needed
as CrCl falls < 60 ml/min, consider empiric dose adjustments
-dose and/or interval can be adjusted
-typically based on broad ranges of CrCl
drug accumulation of clinical relevance if > 50% of drug (or active metabolite) are eliminated by the kidney
What is the acronym to remember drugs which may be of concern in CKD?
BANDD CAMP
beta-blockers
ACEI/ARBs
NSAID
diabetic meds
cholesterol meds
antimicrobials (antibiotics, antivirals, antifungals)
miscellaneous (allopurinol, colchicine, digoxin, H2RAs)
psychotropics
What are some questions to ask yourself when drug dosing in renal impairment?
is the drug safe and effective with reduced renal function?
is the drug nephrotoxic?
does the clinical situation warrant an immediate effect or can we titrate if benefit is not needed immediately?
Describe the stepwise approach for dosing in renal impairment.
- collect a thorough med history (OTC, herbals, rec)
- determine degree of renal impairment
-calculate CrCl and GFR (HD or PD???)
-use multiple equations - assess drug being added
-indication, dose, interval, duration
-nephrotoxic potential?
-method of metabolism/elimination
-AEs - choose less nephrotoxic drugs whenever possible
- determine appropriate dose
-consult multiple references
-consider trends in SCr
-consider clinical status
-consider benefits vs risk - monitor and reassess therapy
-efficacy + toxicity (TDM if available) - monitor SCr and reassess dosing periodically
Describe drug dosing in AKI.
estimations of CrCl/GFR are inaccurate when renal function acutely changing
-rise in SCr lags behind AKI
-decline in SCr lags behind recovery
difficult to determine appropriate dosing
-consider trends in SCr
-benefit vs risk of drug
-availability of monitoring
-etiology of AKI can impact duration
Is it appropriate to use SCr to estimate CrCl in patients receiving HD or PD?
no (lacks accuracy)
-CrCl generally around 10ml/min (residual function)
What should you do for drug dosing in dialysis?
generally not our field, consult specialists
consult references to determine if drug is removed by dialysis
-HD: smaller molecules more likely to be removed, high protein binding less likely to be removed
-PD: will not remove drugs appreciably
