Drug Induced Kidney Dz - EG Flashcards
What is the MC manifestation of drug induced kidney disease (DIKD)
decline in GFR
rise in serum creatine and BUN
Nephrotoxicity is often reversible if…
offending agent is discontinued
How does the kidney maintain glomerular ultrafiltration when renal blood flow is diminished?
vasodilating afferent arterioles & vasoconstricting efferent arterioles
(afferent > glomerulus > efferent)
postrenal impairment
obstruction of urine flow in the collecting tubule, ureter, bladder, or urethra
acute glomerulonephritis
inflammation and damage to the glomerular membrane
acute interstitial nephritis
an allergic reaction, may be caused by a variety of drugs
acute tubular necrosis causes:
nephrotoxic agents
prolonged hypoperfusion
What is the MC presentation of DIKD in hospitalized patients? examples of primary agents that can cause this?
Acute tubular necrosis (ATN)
- aminoglycosides, contrast, amphotericin B, cyclosporin
Name 2 drugs that cause hemodynamically mediated kidney injury
ACEI’s and NSAID’s
Clinical manifestations of Acute allergic interstitial nephritis (AIN)
fever, maculopapular rash, eosinophilia, arthralgia, pyuria, hematuria, proteinuria, oliguria
approx. 14 days after initiation of therapy
List 3 medications affected by pharmacokinetic alterations
Vancomycin
Aminoglycosides
Low-molecular-weight heparins
How does edema affect the distribution of many drugs?
can significantly increase the volume of distribution
What is the MC electrolyte disorder and why is it important to monitor frequently?
HYPERkalemia bc it can lead to life-threatening cardiac arrhythmias
What 2 electrolytes are eliminated by the kidneys and not removed efficiently by dialysis?
Phosphorus
Magnesium
What electrolyte disorder leads to protein catabolism and negative nitrogen balance?
protein metabolism
What 2 conditions cause tubular epithelial cell damage
ATN
osmotic nephrosis
Describe the pathogenesis of Aminoglycoside (AG) nephrotoxicity
- accumulation of high concentrations w/in tubular epithelial cells –> kidney necrosis
- toxicity related to # of cationic groups on molecule (i.e. Neomycin > gentamycin > tobramycin > amikacin)
Describe the clinical presentation AG nephrotoxicity?
- Nonoliguria (>500ml urine production/day)
- evidence of injury w/in 5-10 days of therapy
- gradual rise in serum Cr and BUN & decrease in CrCl
Can a patient make a full recovery of renal function after AG nephrotoxicity if the drug is immediately discontinued?
YES
Risk factors of AG nephrotoxicity
- aggressiveness of AG dosing
- synergistic toxicity w/other nephrotoxins
- preexisting clinical conditions
Best prevention for AG nephrotoxicity
Avoid volume depletion
Pathogenesis of Contrast-induced nephrotoxicity (CIN)
renal ischemia from systemic hypotension and acute vasoconstriction
Clinical presentation for Contrast-induced nephrotoxicity (CIN)
nonoligura (>500ml urine production/day)
injury w/in first 24/48hrs of administration
serum Cr peaks between 3-5 days
recovery after 7-10 days
Risk factors for CIN
- preexisting kidney disease, GFR <60
- decreased renal blood flow
- concurrent use of nephrotoxins (NSAIDS, ACEI’s)
Prevention for CIN
use alternative imaging procedures*
hydration
Pathogenesis of Amphotericin B Nephrotoxicity
- increasing permeability and necrosis
- reduction in renal blood flow exacerbates ischemia
Clinical presentation of Amphotericin B Nephrotoxicity
- Nonoligura (>500ml urine production/day)
- K, Na, & Mg wasting
- dysfunction apparent in 1-2 weeks
- decr. in GFR, rise in serum Cr and BUN
- damage may be irreversible
Prevention of Amphotericin B Nephrotoxicity
switching to liposomal form in high risk pt’s
increase infusion time
alternative antifungal agents (azoles, caspofungin)
Pt’s taking cyclosporine to prevent kidney allograft rejection often need ____, to distinguish transplant rejection from cyclosporine toxicity
A kidney biopsy
Pathogenesis of ACEI and ARB nephrotoxicity
- becomes nephrotoxic particularly when renal blood flow is reduced*
- synthesis of Angiotensin II is decreased
- efferent arteriole remains dilated
- reduced outflow resistance from glomerulus
- decreases hydrostatic pressure in glomerular capillaries
Presentation of ACEI and ARB nephrotoxicity
- decrease in urine output
- acutely reduces GFR
- serum Cr rise 30% w/in 3-5 days
- stabilizes in 1-2 weeks
- reversible upon stopping
Risk factors for ACEI and ARB nephrotoxicity
- patients dependent on renal vasoconstriction to maintain BP and GFR (renal a. stenosis)
- decreased arterial blood volume
Prevention of ACEI and ARB nephrotoxicity
choose shorter acting agent in at risk pt’s…
Captopril, enalapril > lisinopril, benazepril
Management of ACEI and ARB nephrotoxicity
- discontinue if serum Cr increases >30% above baseline over 1-2 wks
- serum Cr and hyperkalemia will resolve over several days
- re-initiation can be attempted after correcting volume depletion
Pathogenesis NSAIDs and COX2 selective nephrotoxicity
- inhibit synthesis of vasodilatory prostaglandins
- unopposed renal vasoconstriction in afferent arteriole
- promotes renal ischemia and GFR reduction
Presentation of NSAIDs and COX2 selective nephrotoxicity
- occurs w/in days of event
- diminished urine output
- weight gain or edema
- elevated serum Cr, BUN, K, and BP
Biggest risk factor for NSAIDs and COX2 selective nephrotoxicity
Age >60
Management of NSAIDs and COX2 selective nephrotoxicity
injury is rarely severe
recovery is usu. rapid
Prevention of NSAIDs and COX2 selective nephrotoxicity
- avoid potent compounds in high risk groups (indomethacin)
- use analgesics w/less PGE inhibition (APAP)
- consider drugs w/short half lives (Sulindac)
- COX-2 agents have similar renal effect (Meloxicam, Celecoxib)
drugs that account for 70% of cases of acute allergic interstitial nephritis
penicillins ciprofloxacin nsaids, cox2 inhibitors PPI's Loop diuretics
What medication causes papillary necrosis?
NSAID’s
What drugs cause chronic interstitial nephritis
Cyclosporine
lithium
Methicillin-induced allergic interstitial nephritis (AIN) pathogenesis
- diffuse infiltrate of lymphocytes, eosinophils, neutrophils
- tubular necrosis is relatively common
Methicillin-induced allergic interstitial nephritis (AIN) clinical presentation
- assoc. w/ beta-lactam abx
- presents 14 days after initiation of therapy
- fever, macropupular rash, eosinophilia, arthralgia, oliguria
Methicillin-induced allergic interstitial nephritis (AIN) management
corticosteroids should be initiated immediately
Intratubular obstruction is caused by which meds?
acyclovir
sulfonamides
methotrexate
nephrolithiasis is caused by which meds?
Sulfonamides
Ciprofloxacin
Amoxicillin
Nitrofurantoin
Examples of intratubular obstruction from crystal nephropathy
precipitation of drug crystals in tubular lumen
hyperuricemia
rhabdomyolysis
Which drugs are highly associated with rhabdomyolysis? and when is risk increased?
HMG-CoA reductase inhibitors (simvastatin, lovastatin)
risk increased w/concurrent CYP34A drugs (Gemfibrozil, Niacin, Erythromycin)
Clinical presentation of nephrolithiasis
pain, hematuria, infection, urinary tract obstruction
GFR not usu. decreased
What drugs are associated with renal vasculitis, thrombosis and cholesterol emboli?
vasculitis and thrombosis –> Hydralazine, methamphetamines
Cholesterol emboli –> Warfarin, thrombolytic agents
How do pt’s with renal vasculitis and thrombosis present?
hematuria, proteinuria, oliguria, red cell casts, and frequently along w/ fever, malaise, myalgias, arthralgias
What are important clues that a pt may have a renal cholesterol emboli?
purple discoloration of the toes
mottled skin over the legs
What is a hallmark sign of glomerular injury?
nephrotic range proteinuria (>3.5g/day) w/ or without a decline in GFR
which meds can lead to glomerular disease?
NSAID’s & COX-2 inhibitors*
gold
lithium
pamidronate
At what level in the nephron does ATN occur?
proximal tubules
What are signs of distal tubular injury?
polyuria from failure to maximally concentrate urine
metabolic acidosis d/t urinary acidification
hyperkalemia from impaired K+ excretion
What are signs of proximal tubular injury?
metabolic acidosis w/ bicarbonaturia
glycosuria in absence of hyperglycemia
What lab test/results indicate a drug-induced AKI?
- increase in serum Cr of greater or equal to 0.3mg/dL or 50% w/in 7 days
- reduction in urine output (oliguria <0.5ml/kg/h for more than 6hrs)
