Renal: Lecture 2 Flashcards
What to look for in drug induced kidney disease?
Still looking for doubling in SCr due to medications
Depends on predisposing factors, not everyone will develop
Combo of drugs that can cause kidney issues
“Triple Whammy” = ACEi + Diuretic + NSAID
“Nephrotoxic quartet” = ACEi, NSAID, Aminoglycosides, radio contrast media
“Triple Whammy”
due to each drug affecting kidney function through different mechanisms
Diuretic will lead to….
decreased fluid volume
ACEi/ARBs will lead to….
Efferent dilation
NSAIDs will lead to….
afferent constriction
What increase Kidney susceptibility to injury
Drug-related factors = what drug does to kidney
Kidney-related factors = what happens in kidney
Host-related factors
Angiotensin II is responsible for ….. of the efferent arteriole
Constriction
Prostaglandins are responsible for ….. of the afferent arteriole
Dilation
Common medications causing Prerenal AKI
NSAIDs
ACE/ARBs
Calcineurin inhib
Renal modulators of Hemodynamic autoregulation
Angiotensin II
Prostaglandins
Endothelin and Norepi
Pre-disposing factors for DI pre renal AKI
Reduced renal blood flow state
Reduced perfusion pressure due to low volume state
Those who relay on renal modulators to keep normal eGFR, these meds will “tip the balance”
How can diuretics/ hyperosmolar radio contrast dyes tip the balance?
decrease blood volume
How can NSAIDs tip the balance?
decrease renal prostaglandins
How can ACEi/ARBs tip the balance?
alter AT2
Which agents alter calcium and endothelin
Radiocontrast agents, Cyclosporine
Which agents cause histamine release with Hypotension
Radiocontrast agents
Risk for NSAIDs is primarily in patients with…
preexisting low flow/volume states or conditions
Prerenal AKI NSAIDs clinical presentation
Low FeNA <1% Low urine Na Urine osm >500 Normal urinalysis BUN:SCr > 20:1 Oliguric (dark, tea-colored pee)
onset 1-5 days of start/dose increase NSAID
time to recovery ~2-7day, based on mechanism of drug
All NSAIDs should be suspect, indomethacin greatest risk
Which NSAID has greatest risk for Prerenal AKI
Indomethacin, most potent
Prevention and Treatment NSAIDs Prerenal AKI
Use analgesics with less PG effect
Use lowest dose of NSAID in high-pt
Avoid potent agents
Discontinue drug, usually reversible state
Prerenal AKI - ACEi/ARBs pathogenesis
Lower the tone of efferent arteriole, which may be maintaining perfusion pressure in select patients
Reduce intraglomerular hydrostatic pressure leading to reduced filtration in select patient
Patients who develop Prerenal AKI from ACEi and ARBs usually have….
Severe renal artery stenosis
CHF
CKD
Pathogenesis of impaired auto regulation with ACEi/ARBs
Blocks AT2 = dilation of efferent arteriole = reduction in back pressure/intraglomerular pressure = decreased perfusion pressure and filtration
Prerenal AKI - ACEi/ARBs Risk factors
CHF CKD (Scr >1.6) Severe renal artery stenosis Concomitant diuretic use concomitant NSAID use Salt restricted diet/hypoantremia
Prevention and Treatment ACEi/ARB pre renal AKI
start low, titrate upward slowly (start sort acting agent)
reduce diuretic dose “diuretic holiday”
Counsel patients what to monitor
Monitor SCr and Serum K
Monitor for more than predictable rise in SCr
How does radiocontrast media cause pre renal AKI?
enhance effects of endothelin (vasoconstriction of afferent), caution in patients with similar predisposing causes
Need to hydrate w/ NaCL prior to dye study
How can loop diuretics and metolazone cause prerenal AKI
Cause dehydration, monitor body weight daily to assess fluid loss
monitor urine color and frequency
Most common drug-induced AKI in inpatient setting?
Drug induced ATN
Most common medications in drug induce ATN
Radiocontrast media
Aminoglycosides
Radiocontrast media associated with…
dialysis
3rd leading cause of inpatient AKI and 34% inpatient mortality
risk factors for ATN w/ Radiocontrast media
underlying diabetic nephropathy or CKD Age >75 CHF Volume depletion Aggressive diuresis
radiocontrast pathogenic mechanism
cause transient pre renal azotemia (via endotelio) and progressive non-oliguric or oliguric ATN
mechanism complex and not fully understood
Which radio contrast media are we generally concerned with?
Ionic monomers and dimers
Contrast induced nephropathy (CIN)
**Defined as increase in SCr by 0.5 mg/dL or 25% from baseline
**Usually begins 24-48hrs after procedure, peak in 3-5 days, returns to baseline in 7-10 days
can extend hospital stay + costs
usually transient and nonoliguric
severe form presents as ATN
CIN Pathogenesis
1st Renal Hemodynamic changes which can progress into direct tubular toxicity, acute tubular necrosis
CIN Risk factors
occurs in <2% pop
Highest Risk: DM w/ SCr >1.5, CrCl <60
Other: Age >75, HF, Hypotension, Volume depletion, anemia, high dose of radiocontrast (>140ml) and repeated doses,
CIN Risk assessment
Chart used to calculate risk of CIN and Risk of Dialysis.
Each risk gets a score and its all added together
CIN preventative Strategies
Avoidance when possible, consider alternative imaging techniques
If pt req contrast: DC metformin and NSAIDs 48hr prior
Gold standard: pre/post hydration start 12hr before/12hr after for high risk patients 1ml/kg/hr NaCL
Has any medical or mechanical treatment been proved to be efficacious in reducing risk of CIN?
No
Crystal Nephropathy mechanism
Precipitation of crystals in distal tubular lumen = obstruct urine flow/create back pressure = illicit interstitial reaction
Common meds causing Crystal Nephropathy
Antibiotics: Ampicillin, cipro, sulfonamides
Antivirals: acyclovir, foscarnet, indinavir
Methotrexate
Triamterene
Risk factors for Crystal Nephropathy
Volume Depletion
CKD
Excessive Dose
IV admin
Preventing postrenal drug induced AKI
DC or reduce dose of drug
ensure adequate hydration
Establish high urine flow
Admin orally when possible
General management of Drug induced KD
short term: stop progression of kidney damage
Long term: restore normal kidney function
General: Stop offending agent avoid concomitant nephrotoxin maintain hydration RRT if needed
