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What role do prostaglandins have in the kidneys?
afferent arteriole dilation
What role does angiotensin II have in the kidney?
efferent arteriole constriction
What is the mechanism by which NSAIDs an COX-2 inhibitors effect the kidneys?
Inhibition of the COX 1 & 2 enzymes results in a decrease in prostaglandin production thereby preventing compensatory dilation of the afferent arteriole
Leads to a reduction in intraglomerular pressure and GFR
How long does it take for pre-renal kidney injury to present?
Within days of initiating therapy
What are the typical findings of pre-renal kidney injury?
1. decreased urine output
2. BUN:SCr > 20:1
What are the risk factors for NSAIDs and COX-2 inhibitors renal injury?
kidney disease/conditions known to decrease renal perfusion
concomitant use of other nephrotoxins
age >65 y/o
dose and duration (ibu > 1200 mg/day)
What prevention strategies can be taken for NSAID and COX-2 kidney injury?
1. use analgesics w/ less or not prostaglandin inhibition (APAP)
2. use miminal effective dose for short durations if need to use a nephrotoxic drug
3. avoidance of other drugs that affect renal hemodynamics
4. monitor SCr/BUN every 1-3 weeks after initiation
What analgesic is the most nephrotoxic?
What analgesic is the least nephrotoxic?
Are COX-2 inhibitors less nephrotoxic than NSAIDs?
What is the management for NSAID and COX-2 renal injury?
1. reversible upon discontinuation of therapy
2. supportive care and volume replacement as clinically indicated
Drug Induced Renal Dysfunction