AKI

AKI definition (based on values)

increase in SCr >26.5 micromol/L within 48hr or

increase in SCr to >1.5 times baseline within the prior 7 days or

urine volume <0.5mg/kg/hr for 6hr

oliguria based on urine output in 24hr

<400mL urine/24hr

anuria based on urine output in 24hr

<50mL urine/24hr

what setting is AKI most commin in

critical care (ICU)

patients at risk of AKI

pre existing renal dysfunction (CKD)

age >65

septic shock

critical illness

chronic disease (heart, liver, lung)

cardiac surgery

cancer

trauma

history of AKI

nephrotoxic med exposure (20%)

what is GFR

estimate of overall kidney functiojn

what is creatinine clearance

measures clearance of creatinine by the kidney over a period of time

used to estimate GFR

why should conventional GFR/CrCL equations not be used in AKI

produce falsely high GFR estimation in early stages and falsely low when resolving

what is prerenal AKI

AKI where the kidney is structurally and functionally intact but is hypoperfused

if prerenal AKI is prolonged and not appropriately managed, what can occur

can lead to ischemic injury of renal tubular cells and to developement of intrinsic AKI

most common cause of intrinsic AKI (50%)

acute tubular necrosis (ATN)

what is intrinsic AKI

structural injury within kidney

what is postrenal AKI

AKI due to obstruction of urine flow at any level in the urinary tract, the obstructing process must involve both kidneys (or one if they only have one functioning kidney)

diagnosis of AKI is based on

serial analysis of urea and SCr ± symptoms

signs and symptoms of AKI

peripheral edema

weight gain

N/V/D/anorexia

mental status changes

fatigue

SOB

pruritis

prerenal AKI specific symptoms

volume depletion, weight loss

postrenal AKI specific symptoms

anuria alternating with oliguria

colicky abdominal pain

physical exam findings of AKI

hypertension, pulmonary edema, rales

prerenal: hypotension/orthosttaic hypotension

AIN: rash

post renal: bladder distention, prostatic enlargement

prerenal AKI physical exam findings

hypotension/orthostatic hypotension

acute interstitial nephritis physical exam findings

rash

post renal AKI physical exam findings

bladder distension (obstruction)

prostatic enlargement

AKI lab tests/findings

elevated SCr (female normal 37-91, 54-114 male)

elevated urea (normal 3-7)

hyperkalemia

metabolic acidosis

decreased GFR

urea:SCr ratio- can delineate prerenal AKI or worsening renal function from intrinsic and post renal

normal ratio is 0.04:1

ratio >0.08:1 suggests dehydration/prerenal

0.04:1 to 0.08:1 usually instrinsic or post renal

brown muddy granular casts is highly indicitave of

ATN

proteinuria is indicitive of

glomerulonephritis or acute interstitial nephritis

eosinophilia is indicitave of

acute interstitial nephritis

WBC or casts are indicitive of

acute interstitial nephiritis or severe pyelonephritis

does every case of AKI have decreased urine output

no

does oliguric or non oliguric AKI have better prognosis

non oliguric

what is fractional excretion of sodium (FENa)

measure of how actively the kidney is reabsorbing Na - normally proximal tubules reabsorbs 99% of filtered Na

what values of fractional excretion of sodium differentiate pre renal from intrinsic AKI

pre renal AKI <1%

intrinsic and post renal >1%

ATN >2%

what does highly concentrated (>500mOsm/L) urine suggest

stimulation of ADH indicating prerenal AKI

intrinsic and post renal AKI urine osmolality values

<350mOsm/L

common AKI diagnostic procedures

urinary catheterization, renal ultrasound, renal angiography, kidney biopsy

AKI prevention

screen and identify those at risk

monitor high risk carefully (esp if additional risk added like acute illness, new drugs)

prevention strategies when appropriate: hydration, loop diuretics for fluid overload, N-acetylcysteine pre contrast, avoid nephrotoxic drugs

which AKI can often be reversed if the underlying problem is promptly identified and corrected

pre and post renal

treatment options for AKI

if drug indcued stop drug

if due to underlying condition, correct condition

intrinsic is supporitive in nature

AKI supportive care

close pt management

fluid, electrolyte, nutritional support

renal replacement therapies (Dialysis)

avoidance of other nephrotoxic drugs

treatment of non renal complications such as pulmonary edema, hyperkalemia, metabolic acidosis, sepsis or GI bleeding

list the drugs used for pharmacological treatment of AKI

loop diuretics

low dose dopamine (studies show no indication for it’s use though)

furosemide

bumetanide

ethacrynic acid

why are loop diuretics useful in AKI

used for volume overload and edema, NOT to hasten renal recovery or improve survival

diuretic of choice for management of volume overload

most common used loop diuretic for AKI

furosemide

benefits of furosemide for AKI

low cost, reasonable safety and efficacy

cons of furosemide for AKI

variable oral bioavailability, potential ototoxicity

how does AKI effect furosemide half life

extends it

furosemide route AKI

po and IV

bumetanide route in AKI

po

benefits of bumetanide over furosemide in AKI

more predictable oral bioavailability, more potent

ethancrynic acid route in AKI

po and IV

when is ethacrynic acid used in AKI

sulfa allergy

why may large doses of loop diuretics be required in AKI

substances which accumulate in AKI can competitively inhibit secretion of loop diuretics therefore larger doses may be needed to ensure enough diuretic gets in lumen

are any loop diuretics more effective than the others

no, all equally effective at equivalent doses

if no response at max dose loop diuretic, will switching to another improve efficacy

no

causes of diuretic resistance in AKI (4)

excessive sodium intake- overrides ability of diuretic to eliminate sodium

nephrotic syndrome- heavy proteinuria binds loop

increased sodium resorption- nephron adaptation

acute tubular necrosis- reduced number of functioning nephrons for diuretic to work on

how can diuretic resistance be overcome

by using continuous infusion instead of bolus dosing (more natriuresis with continous infusion vs bolus at same dose)

examples of thiazide diuretics used in AKI

HCTZ, metolazone

why is thiazide diuretic sometimes added to loop in AKI diuretic resistance

synergy - acts on DCT

ae of loop diuretics

hypotension

dizziness

GI upset (anorexia, N/V/D )

electrolyte disturbances- hypokalemia, hypomagnesiumia, hypocalcemia, hyponatremia

muscle aches and cramps (bc low K and Mg) risk of arrythmias

hyperglycemia, hyperlipidemia (thiazides worse)

hearing loss (high dose loop diuretics only)

photosensitivity

risk of lithium toxicity

monitoring of loop diuretics

BP, volume status/urinary output, electrolytes, SCr, urea

what drugs commonly cause prerenal community acquired AKI

NSAIDs/ COX-2 inhibitors

how do NSAIDs/ COX-2 inhibitors cause AKI

decreased renal perfusion

PGs released and cause afferent arteriole vasodilation- NSAIDs and COX-2i prevent PG synthesis thereby negating compensatory vasodilation

NSAIDs can cause prerenal AKI and also _________

direct renal injury

NSAID/COX-2i induced prerenal AKI clinical presentation

sudden onset oliguria and sodium and water retention at the onset or within several days of starting an NSAID

clinical course of NSAID/COX-2i induced prerenal AKI (reversible/irreversible)

generally reversible when drug is d/c (as long as tubular damage has not occured)

risk factors for pre renal NSAID/cox-2i induced AKI

CHF

elder

diabetes

combo of ACEI/NSAID

CKD

liver disease

dehydrated

hypertension

prevention of prerenal NSAID/COX-2i induced AKI

avoid in pts at highest risk

use lowest possible dose and shortest duration

optimize control of other disease states (CHF, diabetes)

monitor renal function and BP

what type of AKI do ACEI/ARBs cause

prerenal

how do ACEI/ARB cause aki

inhibit ang-II mediated efferent arteriole vasoconstriction

clinical presentation of ACEI/ARB AKI

increase of SCr up to 30% is seen within 3-5 days of starting

stabilizes in 1-2 weeks

what % of an increase in SCr in 1-2wks when starting ACEi/ARB warrants discontinuation of drug

>30%

risk factors of ACEI/ARB aki

bilateral renal artery stenosis

pre existing kidney disease

CHF

volume depletion (dehydration, overdiuresis)

prevention of ACEI/ARB induced aki

measure baseline SCr before initiation

hold diuretics for. afew days before starting

start w/ low dose

monitor SCr and K q 2-3 days for high risk, within 1-2wks for low risk

what type of AKI can cyclosporine and tacrolimus cause

prerenal

how do cyclosporine and tacrolimus cause aki

afferent vasoconstriction and decreased gfr

clinical presentation of cyclosporine / tacrolimus induced aki

may occur within days

hypertension, hyperkalemia, sodium retention, oliguria, acidosis, hypomagnesemia

clinical course of cyclosporine/tacrolimus induced aki

usually imrpoves with dose reduction or stopping interacting drugs

risk factors of tacrolimus and cyclosporine induced aki

high dose

elevated trough blood conc

increased age

volume depletion

use of other nephrotoxic drugs/interacting drugs

prevention of cyclosporine and tacrolimus induced AKI

pharmacokinetic monitoring

monitor for Sx

manage drug interactions

list drugs that can cause intrinsic aki (ATN)

amphotericin B

contrast media

aminoglycosydes

cisplatin, carboplatin

adefivor, cidofovir, tenofovir

pentamadine

foscarnet

zoledronate

mannitol

how does amphotericin b cause ATN

direct tubular epithelial cell toxicity

depletes intracellular conc of Na, K, Mg in distal tubule

ischemic injury due to reduction in renal blood flow

amphotericin b induced ATN clinical presentation

onset ranges from few days to weeks

increased urea and SCr, decreased urine concentrating ability, polyuria, hypokalemia, hypomagnesemia, hematuria, pyuria, casts

risk factors for amphotericin b induced atn

total cumulative dose, esp when dose reaches 4-5g total

CKD, increased age, other nephrotoxins, hypokalemia

prevention of amphotericin B induced atn

sodium loading (500-1000mL 0.9% NaCl pre dose)

avoid diuretics, sodium restriction, dehydration

lipid based AmphoB enhance drug delivery to site of infection and reduce interaction with tubular cells, incidence of nephrotoxicity lower in clinical trials

how does contrast media cause ATN

renal ischemia and direct cellular toxicity

high osmolar agents more likely

clinical presentation of contrast media induced aki

ranges from transient changes to irreversible oliguric renal failure

SCr peaks 3-4 days after exposure, recovery in 7-10 days

urinalysis shows proteinuria, hyaline casts

risk factors for contrast media induced atn

pre existing kidney disease (esp GFR <60)

dehydration

diabetes

advanced age

other neprotoxins

prevention of contrast media induced atn

hydrartion: 0.9% NaCl infusion 12hr pre and post

N-acetylcysteine (600-1200mg po bid day before and day of procedure)

how do aminoglycosides cause atn

high drug conc in proximal tubular cells causes injury and cell death

clinical presentation of aminoglycoside induced atn

nonoliguric, gradual rise in SCr

usually presents 5-10 days after initiation

risk factors for aminoglycoside induced atn

prolonged Tx, high cumulative dose, trough levels >2mg/L, previous AG therapy (previous 30 days)

prevention of aminoglycoside induced atn

individualized pharmacokinetic monitoring

minimize length of Tx

adequate hydration

avoidancce of other nephrotoxins

monitor for changes in renal function

extended interval (once daily) AG dosing

how to platinum derivatives cause ATN

formation of a toxic oxygen free radical species in proximal tubular cells with resultant lysosome, mitochondrial and nucelolar disruption

clinical presentation of platinum derivatives atn

20-30% receiving cisplatin- SCr increase 72-96hr after admin

SCr peaks at 14 days and recovery by 21 days

Mg wasting common

does carboplatin or cisplatin cause more atn

cisplatin

risk factors for platinum derivatives atn

increased age, large cumulative doses, alcohol abuse

prevention of platinum derivate induced atn

cisplatin: aggresive hydration with 0.9% NaCl IV infusion, start 12-24hr pre and continue for 2-3 days post admin

monitor electrolytes, esp Mg

list drugs that can cause acute interstitial nephritis

beta lactam abx

ciprofloxacin

PPI

furosemide

allopurinol

vancomycin

NSAIDs/COX-2i

AIN accounts for _% of all AKI

2

AIN usually manifests how long after exposure

2 wks

classical triad/symptoms of AIN

fever, rash, arthralgia (oliguria, eosinophilia)

**not consisten, 1 or more may be absent

how is NSAID AIN different from typical AIN

usually age 50+, onset delayed (6mo from initiation vs 2wks), fever, rash, eosinophilia typically NOT present

most definitive method for diagnosing AIN

renal biopsy