Toxic Responses of Kidney Flashcards
What functional tasks do the kidneys perform?
- formation of ultra filtrate
- bulk reabsorption
- controls urine concentration- up to 25% of water and solute are reabsorbed
- reabsorbs solute
- fine-tuning in the balance between excretion and reabsorption of water, solute
What are the functions of the kidneys?
- excretion of metabolic wastes
- regulation of: extracellular fluid volume, electrolyte composition, and acid base balance
- synthesis and release of hormones (1,25 dihydroxy vitamin B, renin, erythropoietin)
What percentage of cardiac output does the kidney receive?
20-25%
What makes the kidney esp susceptible to toxicity?
- concentrate toxicants in tubular fluid
- metabolizes xenobiotics
- glomeruli and interstitial are susceptible to attack by the immune system
_____ of acute kidney injuries are secondary to medication use
30%
What are the value definitions of actor kidney injury?
- sCr >1.5x baseline within 7 days
- urine volume <0.5 ml/kg/hr for 6 hours
What is the mechanism of pre-renal injury?
- impaired renal perfusion
- can be caused by bleeding, volume depletion, cardiac dysfunction or vasoconstriction
What medications can cause pre-renal damage?
bleeding: anticoagulants
v. depletion: diuretics, cathartics, emetics
cardiac dysfunction: BB, cardiotoxins
vasocontriction: NSAIDs, calcineurin inhibitors, cyclosporin
What is the mechanism of renal damage?
- intrinsic damage (in vasculature or glomerulus)
- vascular, glomerular, acute tubular necrosis, acute interstitial nephritis
What medications can cause renal damage?
- cyclosporine, tacrolimis, quinine, clopridogrel
- ACE inhibitors, NSAIDs
- acetaminophen, aminoglycosides, antifungals, chemotherapeutic agetns, contrast media
- antimicrobials, NSAIDs, diuretics, antihistamines, PPIs
What is the mechanism of post-renal failure?
- obstruction of urine flow
- kidneys fail rapidly
- bladder dysfunction
- crystal formation
- retroperitoneal fibrosis
What drugs can contribute to post-renal failure?
- anticholinerigics, antipsychotics
- acyclovir, ciprofloxacine, methotrexate, sulfonamides
- B blockers, methyldopa, hydralazine
What are some of the risk factors of kidney injury?
- pre-existing renal impairment
- dehydration
- cirrhosis, HF, DM
- multiple nephrotoxic agents
- seriously ill
- advanced age
What is chronic kidney disease usually caused by?
- DM
- HTN
- secondary pathophysi processes triggered by AKI
- long term exposure to nephrotoxic agents
What NSAIDs are the ones that cause kidney damage?
nonselective NSAIDs or COX-2 specific NSAIDs
What kind of kidney damage do NSAIDs do?
- pre-renal damage
- Acute interstitial nephritis
What clinical manifestations does NSAID kidney injury take on?
- increased plasma creatinine
- decreased RBF and GFR
- oliguria
What is the mechanism in which aminoglycosides cause toxicity?
- proximal tubular necrosis (freely filtered, accumulate in proximal tubule - bind to phospholipids within the plasma membrane as well)
- interstitial nephritis
What dosing changes can be made to avoid amino glycoside toxicity?
1 high dose of amino glycoside rather than TID will prevent toxicity
What are the clinical manifestations of amino glycoside toxicity?
- increased plasma creatinine
- increased BUN
- non-oliguric
- electrolyte abnormalities
What aminoglycosides are the most nephrotoxic vs the least?
gent > tobra > amikacin
What can be done to prevent amino glycoside nephrotoxicity?
- avoid in patients with risk factors
- adjust dose for renal function
- correct hypokalemia and hypomagnesemia
- limit duration to 7-10 days
- minimize other nephrotoxic agents
- choose an amino glycoside with less nephrotoxicity
What is the mechanism of radio-contrast media nephrotoxicity?
- high osmolality, which can lead to acute tubular necrosis and vasoconstriction
What is the clinical manifestation of radio contrast media nephrotoxicity?
- within 24-48 hours post exposure
- mild increase in sCr
- usually non-oliguric
- hyperkalemia, acidosis, hyperphosphatemia
