Transcript Acute Kidney Injury (AKI)

Acute Kidney Injury (AKI)
Pharmacotherapy II
Second Semester
2016/2017
References
 Pharmacotherapy: A Pathophysiologic Approach – eChapter 43(10th ed)
 Applied Therapeutics: The Clinical Use of Drugs – Chapter 30 (10th ed)
 UpToDate: http://www.uptodate.com
 Assessment of kidney function: Serum creatinine; BUN; and GFR
 Diagnostic approach to the patient with acute or chronic kidney disease
 Urinalysis in the diagnosis of renal disease
 Definition of acute kidney injury (acute renal failure)
 National Kidney Foundation: http://www.kidney.org
 The Renal Association. Acute kidney injury. 2011.
http://kdigo.org/home/guidelines/acute-kidney-injury/
 Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group.
KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138
Introduction
 Renal function:
 Maintenance of body composition:
 Filtration
 Reabsorption
 Secretion
 Excretion of metabolic end products and foreign
substances (urea, toxins, drugs)
 Production and secretion of enzymes and
hormones (renin, erythropoietin)
 Activation of vitamin D3/glucneogenesis/metabolism of
insulin, steroids and xenobiotics
Assessment of kidney function
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Introduction
 Patients with kidney disease may have a variety of different clinical
presentations. Some have symptoms that are directly referable to the kidney (gross
hematuria, flank pain) or to extra-renal symptoms (edema, hypertension, signs of
uremia). Many patients, however, are asymptomatic and are noted on routine
examination to have an elevated serum creatinine concentration or an abnormal
urinalysis.
 Once kidney disease is discovered, the presence or degree of kidney dysfunction
and rapidity of progression are assessed, and the underlying disorder is
diagnosed. Although the history and physical examination can be helpful, there are two
major components of the diagnostic approach to the patient with renal disease:
 Assessment of renal function by estimation of the glomerular filtration rate
(GFR), initially by measurement of the plasma creatinine concentration and (in those
with stable renal function) the application of formulas which provide reasonable, but not
precise, estimates of GFR.
 Careful examination of the urine (by both qualitative chemical tests and
microscopic examination), since the urinary findings narrow the differential.
Glomerular filtration rate (GFR)
 The GFR is equal to the sum of the filtration rates in all of the functioning
nephrons  the estimation of the GFR gives an approximate measure of the
number of functioning nephrons.
 The GFR is expressed as the volume of plasma filtered across the glomerulus per
unit time, based on total renal blood flow (1L/min/1.73 m2)and capillary
hemodynamics (plasma volume is 60% of the blood volume).
 The normal value for GFR depends on age, sex, and body size, and is
approximately 130 and 120 mL/min/1.73 m2 for men and women, respectively,
with considerable variation even among normal individuals
 A reduction in GFR implies either progression of the underlying disease or the
development of a superimposed and often reversible problem, such as decreased renal
perfusion due to volume depletion.
 An increase in GFR, is indicative of improvement in renal function, or may imply an
increase in filtration (hyperfiltration) due to hemodynamic factors
 A stable GFR in patients with renal disease implies stable disease.
Estimation of GFR
 GFR cannot be measured directly in humans  use special
solute markers.
 The most common methods utilized to estimate the GFR in
adults are:
 the serum creatinine concentration,
 the creatinine clearance,
 estimation equations based upon the serum creatinine concentration:
 Since all renal disorders variably affect renal function, estimation of the
GFR has no diagnostic utility.
 In addition, serum creatinine and GFR estimation equations can only be
used in patients with stable kidney function. (WHY? …
Homework)
Serum Creatinine
 Creatinine is the standard laboratory marker for the detection of kidney disease.
 The third National Health and Nutrition Examination Survey (NHANES III) revealed a mean
serum creatinine of 0.96 mg/ dL in women, and 1.16 mg/dL in men in the United States.
 There is presently no accepted single standard for an “abnormal” serum creatinine, as it is gender,
race, and age-dependent.
 The serum creatinine concentration alone
is not an optimal measure of kidney
function, however, it is often used as a marker for referral to a nephrologist.
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The concentration of creatinine in serum
is a function of creatinine production
and serum excretion.
 Production is dependent on muscle mass
 Eliminated primarily by glomerular filtration
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At steady state, the normal serum creatinine
conc range is 0.5-1.5 mg/dL for males and
females.
Algorithm for estimating kidney function using eGFR and/or eCLcr
approaches.
CreatClear = UrineCreat * DaysUrineVolume /
SerumCreat / 1440
Blood urea nitrogen (BUN)
 Amino acids metabolized to ammonia are subsequently converted in the liver to urea,
the production of which is dependent on protein availability (diet) and hepatic function.
 Urea undergoes glomerular filtration followed by reabsorption of up to 50% of the
filtered load in the proximal tubule.
 The reabsorption rate of urea is predominantly dependent on the
reabsorption of water. The excretion of urea may, therefore, be decreased under
conditions which necessitate water conservation such as dehydration although the GFR
may be normal or only slightly reduced.
 This condition is evident when a patient exhibits prerenal azotemia, or an increase of the
blood urea nitrogen to a greater extent than the serum creatinine.
 The normal blood urea nitrogen-to-creatinine ratio is 10 to 15:1, and an
elevated ratio is suggestive of a decreased effective circulating volume, which stimulates
increased water, and hence, urea reabsorption.
 The blood urea nitrogen is usually used in combination with the serum
creatinine concentration as a simple screening test for the detection of
renal dysfunction.
Urine sodium excretion
 With acute renal failure, measurement of the urine sodium concentration is helpful
in distinguishing acute tubular necrosis (>40 meq/L) from effective volume depletion
(<20 meq/L)
 The effect of variations in urine volume can be eliminated by calculating the fractional
excretion of sodium (FENa). This is defined by the following equation:
UNa x PCr
FENa, percent = —————— x 100
PNa x UCr
where UCr and PCr are the urine and plasma creatinine concentrations, respectively,
and UNa and PNa are the urine and plasma sodium concentrations, respectively.
 In acute renal failure, the FENa is the most accurate screening test to
differentiate between prerenal disease and acute tubular necrosis.
 a value below 1 percent suggests prerenal disease;
 a value between 1 and 2 percent may be seen with either disorder,
 a value above 2 percent usually indicates ATN.
 By comparison, among patients with chronic kidney disease, the addition of a prerenal
process may not result in a low urine sodium concentration or FeNa.
Urinalysis
 The urinalysis is the most important noninvasive test in the
diagnostic evaluation since characteristic findings strongly
suggest certain diagnoses.
 It can be used to detect and monitor the progression of
diseases such as DM, glomerulonephritis and chronic UTI.
 Urinalysis involves:
 Visual observation (volume and color)
 Microscopic examination of the urinary sediment to determine
formed elements: erythrocytes, leukocytes, casts and crytals.
 Dipstick testing for protein, pH, concentration, glucose, ketones,
hematuria and pyuria.
Urinary pattern
Renal disease
Hematuria with red cell casts, dysmorphic
red cells, heavy proteinuria, or lipiduria
Virtually diagnostic of glomerular disease or
vasculitis
Multiple granular and epithelial cell casts
with free epithelial cells
Strongly suggestive of acute tubular necrosis in a
patient with acute renal failure
Pyuria with white cell and granular or waxy
casts and no or mild proteinuria
Suggestive of tubular or interstitial disease or urinary
tract obstruction
Hematuria and pyuria with no or variable
casts (excluding red cell casts)
May be observed in acute interstitial nephritis,
glomerular disease, vasculitis, obstruction, and renal
infarction
Hematuria alone
Varies with the clinical setting
Pyuria alone
Usually infection; sterile pyuria suggests urinary
tract tuberculosis or tubulointerstitial disease
Few cells with little or no casts or proteinuria In acute renal failure, prerenal disease, urinary tract
(normal or near-normal)
obstruction, hypercalcemia, myeloma kidney, some
cases of acute tubular necrosis, or a vascular disease
with glomerular ischemia but not infarction
(scleroderma, atheroemboli); in chronic renal
failure, nephrosclerosis, urinary tract obstruction,
and tubulointerstitial disease
Urine volume
 the urine output is variable, ranging from oliguria to normal or even
above normal levels.
 The urine output is determined, not by the GFR alone, but by the
difference between the GFR and the rate of tubular reabsorption.
 If, for example, a patient with advanced acute or chronic kidney disease has a
GFR of 5 L/day (versus the normal of 140 to 180 L/day), the daily urine
output will still be 1.5 L if only 3.5 L of the filtrate is reabsorbed.
 The urine output is of little diagnostic value. However, little or
no output is diagnostically useful in the acute setting.
 Causes of this finding include shock, complete bilateral urinary tract
obstruction, renal cortical necrosis, and bilateral vascular occlusion (as
with a dissecting aneurysm or thrombotic thrombocytopenic purpurahemolytic uremic syndrome).
Radiologic studies and Renal biopsy
 A number of radiologic studies are used to evaluate the patient with
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renal disease.
They are principally required to assess urinary tract obstruction, kidney
stones, renal cyst or mass, disorders with characteristic radiographic
findings, renal vascular diseases, and, in children and young adults,
vesicoureteral reflux.
Renal ultrasonography – most commonly used radiologic technique
Helical CT scan – generally preferred with patients with flank pain and
possible urolithiasis.
Magnetic resonance imaging – useful for the assessment of
obstruction, malignancy and renovascular disease.
A renal biopsy is most commonly obtained in patients with suspected
glomerulonephritis or vasculitis and in those with otherwise unexplained
acute or subacute renal failure.
Major causes of kidney disease
 The causes of acute or chronic kidney disease are traditionally
classified by that portion of the renal anatomy most affected by the
disorder.
 Renal function is based upon four sequential steps, which are isolated to specific
areas of the kidney or surrounding structures:
 First, blood from the renal arteries and their subdivisions is delivered to the
glomeruli.
 The glomeruli form an ultrafiltrate, nearly free of protein and blood elements,
which subsequently flows into the renal tubules.
 The tubules reabsorb and secrete solute and/or water from the ultrafiltrate.
 The final tubular fluid, the urine, leaves the kidney, draining sequentially into
the renal pelvis, ureter, and bladder, from which it is excreted through the urethra.
 Renal disease can be caused by any process that interferes with any
of these structures and/or functions.
 Identifying prerenal (reduced renal perfusion) and postrenal (obstructive)
diseases is particularly important because they may be readily reversible.
Disease duration
 There is also a variable time course.
 Acute: a rise in the plasma creatinine concentration or an abnormality on
the urinalysis that has developed within days to weeks represents an acute
process
 Subacute (rapidly progressive): evidence of renal disease extending
for weeks represents a rapidly progressive process
 Chronic: evidence of renal disease extending for months to years is a
chronic process that may be associated with acute exacerbations.
 The determination of disease duration is best performed by comparing
the current urinalysis or plasma creatinine concentration with previous
results, if available.
 the differential diagnosis can frequently be narrowed if the disease
duration is known
Acute Kidney Injury
AKI
 Acute kidney injury (AKI) is a clinical syndrome generally defined
by an abrupt reduction in kidney function as evidenced by changes
in laboratory values, serum creatinine (Scr), blood urea nitrogen
(BUN), and urine output.
Definition and classification of AKI.
In 2004, the Acute Dialysis Quality Initiative (ADQI) group published a consensus-derived definition and
classification system called the Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease
(RIFLE) classification.
 In 2007, a modified version of RIFLE was developed by the Acute Kidney Injury Network (AKIN).
 Both classification systems are now widely accepted and have been validated to predict outcomes in thousands
of patients worldwide.
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RIFLE criteria
consists of:
 three graded levels of
injury (Risk, Injury,
and Failure) based
upon either the
magnitude of elevation
in serum creatinine or
urine output,
 two outcome measures
(Loss and End-stage
renal disease)
*The worst of each
criteria is used
AKIN criteria
 The Acute Kidney Injury Network (AKIN) modified the RIFLE
criteria in order to:
 include less severe ARF,
 impose a time constraint of 48 hours,
 allow for correction of volume status and obstructive causes of ARF prior to
classification.
 The AKIN proposed the term acute kidney injury (AKI) to
represent the entire spectrum of acute renal failure,
recognizing that an acute decline in kidney function is often
secondary to an injury that causes functional or
structural changes in the kidneys and that the injury can have
important consequences for the patient even if it does not lead to
organ failure and a requirement for renal replacement therapy
AKIN criteria
Stage
Serum creatinine criteria
Urine output criteria
1
↑ SCr ≥ 0.3 mg/dL (26.4micromol/L) or
↑ SCr ≥150–200 per cent (1.5–2 fold) from
baseline.
Less than 0.5 mL/kg per
hour for more than 6 hours
2
↑ SCr >200–300 per cent (>2–3 fold) from
baseline.
Less than 0.5 mL/kg per
hour for more than 12 hours
3
↑ SCr >300 per cent (>3fold) from baseline or SCr Less than 0.3 mL/kg per
≥ 4 mg/dL (354micromol/L) with an acute rise of hour for 24 hours or anuria
≥ 0.5 mg/dL (44micromol/L) or treatment with
for 12 hours
renal replacement therapy.
 SCr: Serum creatinine. Only one criterion must be met of either the SCr criteria or the urine output
criteria; if both are present, the criterion which places the patient in the higher stage of AKI is selected.
 The diagnostic criteria should only be applied after volume status has been optimized. Only
one criterion (creatinine or urine output) has to be fulfilled to qualify for a stage.
 Urinary tract obstruction needed to be excluded if oliguria was used as the sole diagnostic criterion.
 Individuals who receive RRT are considered to have met the criteria for stage 3 irrespective of the stage
they are in at the time of RRT.
RIFLE vs AKIN
 While generally similar, there are a few noteworthy differences:
 RIFLE defines AKI as an abrupt (1 to 7 days) but sustained (>24 hours)
decrease in renal function from baseline while AKIN designates a 48hour period for the decrease to occur.
 AKIN removed RIFLE’s last two classification components (Loss of
Kidney Function and End-Stage Kidney Disease [ESKD]) from the
staging system and instead places all patients receiving RRT
automatically into AKIN stage 3.
 AKIN removed all estimated glomerular filtration rate (eGFR) criteria
from its staging system and lowered the absolute increase in Scr from
0.5 mg/dL designated for RIFLE-Risk class to 0.3 mg/dL for AKIN
stage 1.
AKI definition according to KDIGO
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In order to provide a single definition of AKI for practice, research, and public health, a second modification of
RIFLE and AKIN criteria was recently published by the Kidney Disease: Improving Global Outcomes
(KDIGO) Clinical Practice Guidelines working group in 2012.
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KDIGO defines AKI as being present if any of the following three criteria are met:
1.
2.
3.
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Increase in Scr by at least 0.3 mg/dL (27 μmol/L) within 48 hours,
Increase in Scr by at least 1.5 times baseline within the prior 7 days,
Decrease in urine volume to less than 0.5 mL/kg/h for 6 hours.
KDIGO staging of AKI is similar to the RIFLE and AKIN criteria with the notable addition of inclusion of
pediatric patients (<18 years) to KDIGO Stage 3 for those with an estimated GFR of less than 35
mL/min/1.73 m2 as determined by the Schwartz formula. Due to the very recent publication of KDIGO
guidelines, it still remains to be seen if it will supersede RIFLE and AKIN criteria for the diagnosis and
classification of AKI in the future.
Drawbacks
 Since all three staging systems depend on Scr and urine output as the
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main diagnostic criteria, they are associated with the same inherent weaknesses.
An increase in Scr is usually evident about 1 or 2 days after development of
AKI. This lag time in Scr rise may significantly delay diagnosis of AKI and
adversely affect patient outcomes.
Urine output reduction emerges earlier in AKI but is a very nonspecific
marker because it may not always be present. In fact, patients with AKI can be
anuric (urine output <50 mL/day), oliguric (urine output <500 mL/day), or
nonoliguric (urine output >500 mL/day). Urine output will also vary with
volume status, diuretic administration, and presence of obstruction.
Further, since all criteria are based on detecting a decrease in Scr from its
baseline, a patient’s renal function prior to the development of AKI needs to
be known.
If the baseline measure of Scr is not available and the patient has no
history of renal dysfunction, the ADQI, a workgroup composed of experts in
nephrology and critical care, has suggested estimating the baseline Scr value by
using the four variable MDRD equation with an assumed normal GFR of 75
mL/min/1.73 m2. However, this method needs to be interpreted with caution
as it has been found to overestimate the incidence of AKI by as much as 40%.
Glomerular filtration rate (GFR; mL/min) and serum creatinine (Scr; mg/dL)
versus time following the insult that leads to acute kidney injury (AKI).
Epidemiology
 The epidemiology of AKI varies widely depending on the patient
population, geographical location, and the criteria used to evaluate
the patient.
Etiology
 The etiology of AKI can be divided into broad categories based on the anatomic location
of the injury associated with the precipitating factor(s).
 The management of patients presenting with this disorder is largely predicated on
identification of the specific etiology responsible for the patient’s AKI.
 Traditionally, the causes of AKI have been categorized as:
(a)
(b)
(c)
prerenal, which results from decreased renal perfusion in the setting of undamaged
parenchymal tissue,
intrinsic, the result of structural damage to the kidney, most commonly the tubule
from an ischemic or toxic insult,
postrenal, caused by obstruction of urine flow downstream from the kidney
 Community-acquired AKI most commonly occurs secondary to renal
hypoperfusion from volume depletion (dehydration, vomiting, and diarrhea), sepsis, or
medications (angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor
blockers [ARBs], and diuretics).The most common cause of hospital- and ICUacquired AKI is intrinsic, occurring as the result of acute tubular necrosis (ATN).
Risk factors for development of AKI
Comorbidities
Advanced age
Diabetes
CKD
Heart failure
Liver failure
Male gender
Genetic factors
Low albumin
Arterial disease
Myeloma
Clinical conditions
Sepsis
Hypotension/shock
Volume depletion
Rhabdomyolysis
Cardiac/vascular surgery
Non-renal solid organ
transplant
Drugs
Contrast media
Antibiotics
Chemotherapy
NSAID
ACE inhibitor/ARB
Hepatic/biliary surgery
The exact etiology of AKI is not always obvious and
occasionally more than one factor contributes to its
development.
Prognosis
 In patients with AKI, the chances of renal recovery and survival
depend on:
 the underlying etiology,
 the duration of AKI
 associated comorbidities.
 There is increasing recognition that AKI is associated with an
increased risk of dying even after discharge from hospital.
 AKI due to ATN is usually reversible. However, several reports have
highlighted an association between AKI and subsequent risk of
developing CKD, even if the episode of AKI resolves and serum
creatinine returns to baseline.
Pathophysiology
 There are typically three categories of AKI:
 Prerenal AKI
 Intrensic AKI
 Postrenal AKI
 The pathophysiologic mechanisms differ for each of the categories.
 pseudorenal kidney injury does not represent a true
pathophysiologic process.
Prerenal AKI
 characterized by reduced blood delivery to the kidney.
 The integrity of the renal parenchyma is not disrupted.
 A common cause is intravascular volume depletion due to conditions such as
hemorrhage, dehydration, or gastrointestinal fluid losses.
 Prompt correction of volume depletion can restore renal function to normal because no
structural damage to the kidney has occurred.
 Conditions of reduced cardiac output (e.g., congestive heart failure or
myocardial infarction) and hypotension can also reduce renal blood flow, resulting in
decreased glomerular perfusion and prerenal AKI.
 the kidney initially compensates for the diminished perfusion to preserve
filtration function. With a mild to moderate decrease in renal blood flow,
intraglomerular pressure is maintained by dilation of afferent arterioles (arteries
supplying blood to the glomerulus), constriction of efferent arterioles (arteries
removing blood from the glomerulus), and redistribution of renal blood flow to the
oxygen-sensitive renal medulla.
 When renal compensation is maximized and the conditions causing
hypoperfusion remain uncorrected, renal compensation becomes
decompensation, and AKI occurs.
Normal glomerular autoregulation serves to
maintain intraglomerular capillary hydrostatic
pressure, glomerular filtration rate (GFR), and,
ultimately, urine output. (A II, angiotensin II;
PGE2, prostaglandin E2; RBF, renal blood flow.)
Glomerular autoregulation during
“prerenal” states (i.e., reduced blood
flow). (A II, angiotensin II; GFR, glomerular
filtration rate; PGE2, prostaglandin E2; RBF,
renal blood flow.)
Prerenal AKI – cont’d
 Functional AKI occurs when these adaptive mechanisms are compromised and is often caused
by drugs.
 Nonsteroidal anti-inflammatory drugs (NSAIDs) impair prostaglandin-mediated dilation of afferent
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arterioles.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit
angiotensin II–mediated efferent arteriole vasoconstriction.
Cyclosporine and tacrolimus, especially in high doses, are potent renal vasoconstrictors.
All of these agents can reduce intraglomerular pressure (glomerular hydrostatic
pressure which is the driving force for the formation of ultrafiltrate), with a resultant
decrease in GFR.
Prompt discontinuation of the offending drug can often return renal function to normal.
 Other causes of prerenal AKI are renovascular obstruction (e.g., renal artery stenosis),
hyperviscosity syndromes (e.g., multiple myeloma), or systemic vasoconstriction (e.g.,
hepatorenal syndrome).
 Prerenal AKI occurs in approximately 10% to 25% of patients diagnosed with AKI.
Pathogenesis of angiotensin-converting enzyme inhibitor (ACEI) nephropathy.
(A II, angiotensin II; GFR, glomerular filtration rate; PGE2, prostaglandin E2; RBF,
renal blood flow.)
Intrarenal AKI = Intrinsic renal failure
 Caused by diseases that can affect the integrity of the tubules, glomerulus,
interstitium, or blood vessels. Damage is within the kidney; changes in kidney
structure can be seen on microscopy.
 The most common cause of intrinsic renal failure is Acute Tubular Necrosis
(ATN) and it accounts for approximately 50% of all cases of AKI.
 ATN represents a pathophysiologic condition that results from toxic
(aminoglycosides, contrast agents, or amphotericin B) or ischemic insult to the
kidney.
 ATN results in necrosis of the proximal tubule epithelium and basement membrane,
decreased glomerular capillary permeability, and backleak of glomerular filtrate into
the venous circulation.
 Maintenance of ATN is mediated by intrarenal vasoconstriction.
 Glomerular, interstitial, and blood vessel diseases may also lead to
intrinsic AKI, but occur with a much lower incidence. Examples include
glomerulonephritis, systemic lupus erythematosus, interstitial
nephritis, and vasculitis.
 In addition, prerenal AKI can progress to intrinsic AKI if the
underlying condition is not promptly corrected.
Schematic of acute tubular necrosis (ATN). The process is initiated by ischemia or
nephrotoxin exposure that leads to tubular cell death. The cellular debris sloughs off and
obstructs the proximal tubule lumen. Once the nephron is obstructed, a backleak of
the glomerular ultrafiltrate occurs across the tubular basement membrane and
impairment of glomerular filtration.
During the recovery phase of ATN, the obstructive cellular casts are released into the urine
and filtration begins to normalize. GFR, glomerular filtration rate.
Postrenal AKI = obstructive uropathy
 Postrenal AKI accounts for less than 10% of cases of AKI.
 Postrenal AKI is due to obstruction of urinary outflow
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anywhere from the renal pelvis to the urethra.
The development of renal insufficiency in patients without intrinsic
renal disease requires bilateral obstruction (or unilateral
obstruction with a single functioning kidney)
Causes include prostatic disease (hyperplasia or cancer),
metastatic cancer, or precipitation of renal calculi.
The time course can be acute or chronic.
Rapid resolution of postrenal AKI without structural damage to the
kidney can occur if the underlying obstruction is corrected.
Drug Induced AKI
 Homework
 Discuss the mechanism of
nephrotoxicity of the following
drugs:
 Aminoglycosides
 Amphotericin B
 Radiocontrast media
 Cyclosporine and Tacrolimus
 Angiotensin-Converting Enzyme
Inhibitors and Angiotensin Receptor
Blockers
 Non-steroidal Anti-Inflammatory
Drugs
Clinical Presentation
 The initiating signs or symptoms prompting the clinical suspicion of AKI is highly variable.
 Depending on the underlying cause of AKI, patients may present with a variety of symptoms
affecting virtually any organ system of the body.
 Constitutional symptoms such as nausea, vomiting, fatigue, malaise, and weight gain are
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common but nonspecific.
The onset of flank pain is suggestive of a urinary stone; however, if bilateral, it may suggest
swelling of the kidneys secondary to acute glomerulonephritis or AIN.
Complaints of severe headaches may suggest the presence of severe hypertension and vascular
damage.
The presence of fever, rash, and arthralgias may be indicative of drug-induced AIN or lupus
nephritis.
An acute change in urinary habits is another common and noticeable symptom associated with
AKI.
 The presence of cola-colored urine is indicative of blood in the urine, a finding commonly associated with
acute glomerulonephritis.
 In hospitalized patients, changes in urine output may be helpful in characterizing the cause of the patient’s
AKI.
 Acute anuria is typically caused by either complete urinary obstruction or a catastrophic event (e.g.,
shock or acute cortical necrosis).
 Oliguria, which often develops over several days, suggests prerenal azotemia,
 nonoliguric renal failure usually results from acute intrinsic renal failure or incomplete urinary
obstruction.
Diagnosis
 Early recognition and cause identification are critical, as they
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directly affect the outcome of AKI.
One of the first steps in the diagnostic process is to determine if the
renal complication is acute, chronic, or the result of an acute
change in a patient with known CKD (also called acute-on-chronic
renal failure).
Patients should also be promptly evaluated for any changes in their
fluid and electrolyte status.
Patients presenting with AKI in the outpatient environment may
have very nonspecific or seemingly unrelated symptoms so that the
time of onset of the injury can be difficult to determine.
On the other hand, AKI in hospitalized patients is often detected
much earlier in its course due to frequent laboratory studies and
daily patient assessment.
Patient Assessment
 The assessment of a patient with AKI starts with a thorough review of his or
her medical records, with a particular focus on:
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chronic conditions,
medication history,
laboratory studies,
procedures, and surgeries.
An exhaustive review of prescription and nonprescription medicines, herbal
products, and recreational drugs may help determine if AKI was potentially
precipitated by drug ingestion.
 During the initial patient evaluation, presumptive signs and symptoms of
AKI need to be differentiated from a potential new diagnosis of
CKD.
 A past medical history for renal disease–related chronic conditions (e.g., poorly
controlled hypertension and diabetes mellitus), previous laboratory data
documenting the presence of proteinuria or an elevated Scr, and the finding of
bilateral small kidneys on renal ultrasonography suggest the presence of CKD rather
than AKI.
 note that patients with CKD may develop episodes of AKI as well. In that case, an
abrupt rise in the patient’s baseline Scr is one of the most useful indicators of the
presence of an acute insult to the kidneys.
Patient Assessment
 A thorough physical examination is an important step in evaluating
individuals with AKI, as clues regarding the etiology can be evident
from the patient’s head (eye examination) to toe (evidence of
dependent edema) assessment. Observations will either support or
refute the cause as prerenal, intrinsic, or postrenal.
 Evaluation of the patient’s volume and hemodynamic status is
critical as well, as it will guide management. For example, patients
with prerenal AKI can present with either volume depletion or fluid
overload.
 Volume depletion may be evidenced by the presence of postural
hypotension, decreased jugular venous pressure (JVP), and dry mucous
membranes.
 Fluid overload, on the other hand, is often reflected by elevated JVP,
pitting edema, ascites, and pulmonary crackles.
Physical Examination Findings in AKI
Roth spots
Splinter hemorrhage
Diagnostic work-up of patients with AKI
Investigations
Comments
To be performed during initial assessment in primary care
Urinalysis
Serum creatinine and UAEs
FBC and blood film
CRP
Presence of blood, protein and red cell casts suggest a glomerular
cause;
eosinophils suggest an interstitial nephritis.
To diagnose degree of AKI and electrolyte disturbances.
Red cell fragments and thrombocytopaenia support the diagnosis of
thrombotic microangiopathy;
eosinophilia may be present with interstitial nephritis.
May be elevated in inflammatory diseases and/or infections.
Laboratory Tests
 Elevated serum creatinine concentration
 (normal range approximately 0.6 to 1.2 mg/dL [53 to 106 µmol/L])
 Elevated BUN concentration
 (normal range approximately 8 to 25 mg/dL [2.9 to 8.9 mmol/L])
 Decreased creatinine clearance
 (normal 90 to 120 mL/minute)
 BUN:creatinine ratio (elevated in prerenal AKI)
 Greater than 20:1 (prerenal AKI)
 Less than 20:1 (intrinsic or postrenal AKI)
 Hyperkalemia
 Metabolic acidosis
Urinalysis
 Sediment
 Scant or bland (prerenal or postrenal
AKI)
 Brown, muddy granular casts (highly
indicative of ATN)
 Proteinuria (glomerulonephritis or
allergic interstitial nephritis)
 Eosinophiluria (acute interstitial
nephritis)
 Hematuria/red blood cell casts
(glomerular disease or bleeding in urinary
tract)
 White blood cells or casts (acute
interstitial nephritis or severe
pyelonephritis)
Common Diagnostic Procedures
 Urinary catheterization (insertion of a catheter into a patient’s
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bladder; an increase in urine output may occur with postrenal
obstruction)
Renal ultrasound (uses sound waves to assess size, position, and
abnormalities of the kidney; dilatation of the urinary tract can be
seen with postrenal AKI)
Renal angiography (administration of intravenous contrast dye
to assess the vasculature of the kidney)
Retrograde pyelography (injection of contrast dye into the
ureters to assess the kidney and collection system)
Kidney biopsy (collection of a tissue sample of the kidney for the
purpose of microscopic evaluation; may aid in the diagnosis of
glomerular and interstitial diseases)
Treatment of AKI
Supportive care is the mainstay of AKI management regardless of etiology.
The slow process of renal recovery cannot begin until insults are eliminated. This
may be prolonged if the kidney is exposed to repeated insults.
Desired Outcomes
 Short-term goals of AKI management include:
 minimizing the degree of insult to the kidney,
 reducing extrarenal complications,
 expediting the patient’s recovery of renal function.
 The ultimate goal is to have the patient’s renal function restored to his or her pre-AKI
baseline.
 The desired outcome in patients with AKI is to facilitate renal recovery and
minimize injury.
 Renal recovery is facilitated by:
 ensuring that hemodynamic parameters and blood chemistries are monitored daily and maintained
within normal range.
 Fluid status should be monitored by following fluid ins and outs and patient weight as both excessive
and insufficient fluid administration can be detrimental to patient recovery.
 Renal injury can be minimized by:
 careful daily review of patient medications with the goal of avoiding nephrotoxic drugs and adjusting
the dosing of renally eliminated medications.
 Patients receiving RRT need to have their medication administration and serum concentration
measurement times adjusted appropriately with regards to the timing and duration of their RRT.
Things you will need to watch for in practice:
 Is the AKI drug-induced?
 Ischemia
 Inflammation
 sclerosis
 How should AKI be treated?
 How can AKI be prevented?
 How should drugs be dosed in AKI?
Stage-based management of AKI (KDIGO)
 Shading of boxes indicates priority of action—solid shading indicates actions that are equally
appropriate at all stages whereas graded shading indicates increasing priority as intensity increases.
Management of AKI
 There is no evidence that drug therapy hastens patient recovery
in AKI, decreases length of hospitalization, or improves survival.
options are limited to:
 supportive therapy, such as fluid, electrolyte, and nutritional support,
 renal replacement therapy (RRT),
 treatment of non-renal complications such as sepsis and gastrointestinal bleeding
while regeneration of the renal epithelium occurs.
 prevention of adverse drug reactions by discontinuing nephrotoxic drugs or
adjustment of drug dosages based on the patient’s renal function is desired.
Supportive therapy
 Supportive therapy – includes:
 adequate nutrition,
 correction of electrolyte and acid-base abnormalities (particularly
hyperkalemia and metabolic acidosis),
 fluid management,
 correction of any hematologic abnormalities.
 because AKI is often associated with multiorgan failure, treatment
includes the medical management of infections, cardiovascular and
gastrointestinal conditions, and respiratory failure.
 all drugs should be reviewed, and dosage adjustments made based on
an estimate of the patient’s glomerular filtration rate.
Correction of volume depletion
 Moderately volume-depleted patients can be given oral rehydration
fluids; however, if IV fluid is required, isotonic saline is preferred, and
large volumes may be necessary for adequate fluid resuscitation.
 In septic patients, IV fluid challenges are initiated with up to 1,000 mL of
isotonic saline over 30 minutes if tolerated with an assessment of the
volume status after each challenge.The patient should be monitored for
pulmonary edema, peripheral edema, adequate blood pressure (target
mean arterial pressure ≥65 mm Hg), normoglycemia, and electrolyte
balance. Urine output ≥0.5 mL/kg/h is generally targeted during the
initial fluid resuscitation phase.
 In patients with anuria or oliguria, slower rehydration, such as 250 mL
boluses or 100 mL/h infusions of isotonic saline or a balanced crystalloid
solution, should be considered to reduce the risk for pulmonary edema,
especially if heart failure or pulmonary insufficiency exists.
Correction of volume depletion
 Isotonic saline has been associated with hyperchloremic metabolic acidosis and acid–
base imbalance if the dehydration is accompanied by a severe electrolyte imbalance
amenable to large and relatively rapid infusions. For example, dehydration resulting
from severe diarrhea is often accompanied by metabolic acidosis caused by bicarbonate
losses. A reasonable IV rehydration fluid in this situation would be 5% dextrose with
0.45% sodium chloride plus 50 mEq (50 mmol) of sodium bicarbonate per liter,
administered as boluses as described above, followed by a brisk continuous infusion (200
mL/h) until rehydration is complete, acidosis corrected, and diarrhea resolved. This
fluid will remain mostly in the intravascular space, providing the necessary perfusion
pressure to the kidneys, as well as a substantial amount of bicarbonate to correct the
acidosis.
 If the prerenal AKI is a result of blood loss or is complicated by symptomatic anemia,
red blood cell transfusion to a hematocrit no higher than 30% (0.30) is the treatment of
choice.
 Although albumin is sometimes used as a resuscitative agent, its use should be limited to
individuals with severe hypoalbuminemia (e.g., liver disease and nephritic syndrome)
who are resistant to crystalloid therapy. These patients have severe hypoalbuminemiaassociated third spacing that complicates fluid management, and albumin may be useful
in this setting.
Fluid and electrolyte management
 Fluid and electrolyte status will need to be assessed regularly and individualized.
 At times, drug infusions and nutrition solutions may need to be maximally
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concentrated. Maintenance IV infusions should be minimized unless the patient
is euvolemic or is receiving RRT to maintain fluid balance.
Supportive care goals include maintenance of adequate cardiac output and blood
pressure to allow adequate tissue perfusion.
A fine balance must be maintained in anuric and oliguric patients unless the
patient is hypovolemic or is able to achieve fluid balance via RRT.
If fluid intake is not minimized, edema may rapidly develop, especially in
hypoalbuminemic patients.
Excessive fluid administration can also impair the function of other organ
systems and reduce outcomes.
In critically ill patients with vasomotor shock, vasopressors such as
norepinephrine, vasopressin, or dopamine may be used in conjunction with
fluids in order to maintain adequate hemodynamics and renal perfusion.
Renal replacement therapy (RRT)
 RRT may be necessary in patients with established AKI
 to treat volume overload that is unresponsive to diuretics,
 to minimize the accumulation of nitrogenous waste products,
 correct electrolyte and acid-base abnormalities while renal function recovers.
 There are two types of dialysis modalities commonly used in AKI:
 intermittent hemodialysis (IHD)
 continuous renal replacement therapy (CRRT).
RRT
RRT
Several renal replacement therapies are commonly used in
patients with AKI, including one of the three primary
continuous renal replacement therapy (CRRT) variants:
a)
continuous venovenous hemofiltration (CVVH),
b)
continuous venovenous hemodialysis (CVVHD),
c)
continuous venovenous hemodiafiltration
(CVVHDF), and the hybrid intermittent
hemodialysis therapy
d)
sustained low-efficiency dialysis (SLED).
The blood circuit in each diagram is represented in red, the
hemofilter/dialyzer membrane is yellow, and the
ultrafiltration/dialysate compartment is brown. Excess body
water and accumulated endogenous waste products are
removed solely by convection when CVVH is employed.
With CVVHD, waste products are predominantly removed
as the result of passive diffusion from the blood, where they
are in high concentration to the dialysate. The degree of fluid
removal that is accomplished by convection is usually
minimal. CVVHDF uses convection to a degree similar to
that employed during CVVH as well as diffusion, and thus is
often associated with the highest clearance of drugs and
waste products.
Finally, SLED employs lower blood and dialysate flow rates
than intermittent hemodialysis (IHD), but because of its
extended duration, it is a gentler means of achieving
adequate waste product and fluid removal. (Intermediate
between Cont. RRT and Intermittent IHD)
Supportive therapy
 GLYCEMIC CONTROL
 In critically ill patients, we suggest insulin therapy targeting plasma glucose
110–149 mg/dl (6.1–8.3 mmol/l). (2C)
 NUTRITIONAL ASPECTS
 We suggest achieving a total energy intake of 20–30 kcal/kg/d in patients
with any stage of AKI. (2C)
 We suggest providing nutrition preferentially via the enteral route in patients
with AKI. (2C)
 We suggest administering 0.8–1.0 g/kg/d of protein in noncatabolic AKI
patients without need for dialysis (2D), 1.0–1.5 g/kg/d in patients with AKI
on RRT (2D), and up to a maximum of 1.7 g/kg/d in patients on continuous
renal replacement therapy (CRRT) and in hypercatabolic patients. (2D)
 We suggest to avoid restriction of protein intake with the aim of preventing
or delaying initiation of RRT. (2D)
Pharmacologic Therapy
 To date, no pharmacologic approach to reverse the decline or
accelerate the recovery of renal function has been proven to be
clinically useful.
 Many drugs have looked promising in animal trials, only to be
found ineffective in human trials. Other agents have been
investigated and shown no benefit in the treatment of established
AKI.
 For example, loop diuretics are very effective in reducing fluid
overload but can also worsen AKI.
 Prevention of pulmonary edema is an important goal, and it is
preferable that it be accomplished with diuretics instead of more
invasive RRTs, despite the previously mentioned finding that diuretic
use may be associated with diminished outcomes.
Loop diuretics
 There is significant controversy over the role of loop diuretics in the treatment of
AKI.
 Theoretical benefits in hastening recovery of renal function include:
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decreased metabolic oxygen requirements of the kidney,
increased resistance to ischemia,
increased urine flow rates that reduce intraluminal obstruction and filtrate backleak,
renal vasodilation.
 Theoretically, these effects could lead to:
 increased urine output,
 decreased need for dialysis,
 improved renal recovery,
 increased survival.
 Most studies demonstrate an improvement in urine output, but with no effect on
survival or need for dialysis.
 There are some reports that loop diuretics may worsen renal function. This may be due
in part to excessive preload reduction that results in renal vasoconstriction.
 Thus, loop diuretics are limited to instances of volume overload and edema
and are not intended to hasten renal recovery or improve survival.
Loop diuretics – the agents
 furosemide, bumetanide, torsemide, and ethacrynic acid
 all equally effective when given in equivalent doses  Patients will not benefit from
switching from one loop diuretic to another (similar MOA)
 A usual starting dose of IV furosemide for the treatment of AKI is 40 mg. Reasonable
starting doses for bumetanide and torsemide are 1 mg and 20 mg, respectively.
 selection is based on the side-effect profile, cost, and pharmacokinetics of the
agents.
 Cost:
 Furosemide and bumetanide are both available in generic formulations and are generally less
expensive than torsemide.
 Side effects:
 The incidence of ototoxicity is significantly higher with ethacrynic acid compared to the other
loop diuretics; therefore, its use is limited to patients who are allergic to the sulfa
component in the other loop diuretics.
 While ototoxicity is a well-established side effect of furosemide, its incidence is greater when
administered by the intravenous route at a rate exceeding 4 mg per minute.
 Torsemide has not been reported to cause ototoxicity.
 There are several pharmacokinetic differences between loop diuretics.
 50-60% of a dose of furosemide is excreted unchanged by the kidney with the remainder undergoing
glucuronide conjugation in the kidney.
 patients with AKI may have a prolonged half-life of furosemide.
 liver metabolism accounts for 50% and 80% of the elimination of bumetanide and torsemide,
respectively.
 The bioavailability of both torsemide and bumetanide is higher than for furosemide. The intravenous
(IV):oral ratio for bumetanide and torsemide is 1:1, bioavailability of oral furosemide is approximately
50%, with a reported range of 10% to 100%.
 Pharmacodynamic properties
 The pharmacodynamic characteristics of loop diuretics are similar when equivalent doses are
administered.
 Because loop diuretics exert their effect from the luminal side of the nephron, urinary
excretion correlates with diuretic response. Substances that interfere with the organic acid pathway,
such as endogenous organic acids which accumulate in renal disease, competitively inhibit secretion of
loop diuretics. Therefore, large doses of loop diuretics may be required to ensure that adequate drug
reaches the nephron lumen.
 loop diuretics have a ceiling effect where maximal natriuresis occurs. Thus, very large doses of
furosemide (e.g., 1 g) are generally not considered necessary and may unnecessarily increase the risk of
ototoxicity.
Loop diuretics – Diuretic resistance
 Several adaptive mechanisms by the kidney limit effectiveness of loop
diuretic therapy.
 As the concentration of diuretic in the loop of Henle decreases,
postdiuretic sodium retention occurs.
 This effect can be minimized by decreasing the dosage interval or by
administering a continuous infusion (easier).
 Prolonged administration  enhanced delivery of sodium to the distal
tubule  hypertrophy of distal convoluted cells  increased sodium
chloride absorption occurs in the distal tubule which diminishes the
effect of the loop diuretic on sodium excretion.
 Addition of a distal convoluted tubule diuretic, such as metolazone or
hydrochlorothiazide, to a loop diuretic can result in a synergistic increase
in urine output.
Management of fluid overload in AKI
 Loop diuretics are the diuretics of choice for the management of
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volume overload in AKI.
Others?????
Thiazide diuretics, when used as single agents, are generally not
effective for fluid removal when creatinine clearance is less than 30
mL/minute.
Mannitol, which works as an osmotic diuretic, can only be given
parenterally. A typical starting dose of mannitol (20%) is 12.5 to 25 g
infused IV over 3 to 5 minutes. It has little nonrenal clearance, so when
given to anuric or oliguric patients, mannitol can potentially cause a
hyperosmolar state. Additionally, mannitol may cause AKI itself, so its use
in AKI must be monitored carefully by measuring urine output and serum
electrolytes and osmolality
Potassium-sparing diuretics, which inhibit sodium reabsorption
in the distal nephron and collecting duct, are not sufficiently
effective in removing fluid. In addition, they increase the risk of
hyperkalemia in patients already at risk.
Loop diuretics – Monitoring
 Efficacy of diuretic administration can be determined by comparison of a
patient’s hourly fluid balance.
 Other methods to minimize volume overload, such as fluid restriction
and concentration of IV medications, should be initiated as needed.
 If urine output does not increase to about 1 mL/kg per hour, the dosage can be
increased to a maximum of 160 to 200 mg of furosemide or its equivalent.
 Other methods to improve diuresis can be initiated sequentially, such as:
(1) shortening the dosage interval;
(2) adding hydrochlorothiazide or metolazone;
(3) switching to a continuous infusion loop diuretic.
A loading dose should be administered prior to both initiating a continuous
infusion and increasing the infusion rate.
 When high doses of loop diuretics are administered, especially in combination
with distal convoluted tubule diuretics, the hemodynamic and fluid status
of the patient should be monitored every shift, and the electrolyte status of
the patient should be monitored at least daily to prevent profound diuresis and
electrolyte abnormalities, such as hypokalemia.
Algorithm for treatment of extracellular fluid expansion
Algorithm for treatment of extracellular fluid expansion
Cont’d from previous slide
Dopamine
 Low-dose dopamine, in doses ranging from 0.5 to 3 mcg/kg per minute,
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predominantly stimulates dopamine-1 receptors, leading to renal vascular
vasodilation and increased renal blood flow.
While this effect has been substantiated in healthy, euvolemic individuals with
normal kidney function, a lack of efficacy data exists in patients with AKI.
Low-dose dopamine is not without adverse reactions and most studies have
failed to evaluate its potential toxicities (What are these adverse
reactions).
Based on the results of the ANZICS trial, the lack of conclusive evidence in
many earlier studies, and several meta-analyses, routine use of low-dose
dopamine solely for increasing renal blood flow is not
recommended.
While recent surveys continue to show that low-dose dopamine is used in
many ICUs, benefits of low-dose dopamine in the prevention or treatment
of AKI remain unproven.
Fenoldopam
 Fenoldopam is a selective dopamine-1 receptor agonist that is approved
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for short-term management of severe hypertension.
Because it does not stimulate dopamine-2, α-adrenergic, and ß-adrenergic
receptors, fenoldopam causes vasodilation in the renal vasculature with
potentially fewer non-renal effects than dopamine.
In normotensive individuals with normal kidney function, intravenous
fenoldopam increases renal blood flow without lowering systemic blood
pressure.
Few studies are available assessing its effectiveness in the treatment of AKI. A
prospective randomized study comparing fenoldopam to placebo in early
ATN did not find a difference in need for dialysis or mortality.
However, in two separate subset analyses, patients with ATN after cardiothoracic
surgery and patients without diabetes mellitus demonstrated a decreased
incidence of death or dialysis in the fenoldopam treated group.
Large, prospective trials are needed before fenoldopam can be
recommended.
Other agents that are under evaluation for the treatment of AKI include atrial
natriuretic peptide, urodilatin, and nesiritide.
Patient Care and Monitoring
Assess kidney function by evaluating a patient’s signs and symptoms,
laboratory test results, and urinary indices. Calculate a patient’s creatinine
clearance to evaluate the severity of kidney disease.
Obtain a thorough and accurate drug history, including the use of
non-prescription drugs such as NSAIDs.
Evaluate a patient’s current drug regimen to:
1.
2.
3.
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4.
Determine if drug therapy may be contributing to AKI. Consider not only drugs
that can directly cause AKI (e.g., aminoglycosides, amphotericin B, NSAIDs,
cyclosporine, tacrolimus, ACE inhibitors, and ARBs), but also drugs that can
predispose a patient to nephrotoxicity or prerenal AKI (i.e., diuretics
and antihypertensive agents).
Determine if any drugs need to be discontinued, or alternate drugs selected, to
prevent worsening of renal function.
Adjust drug dosages based on the patient’s creatinine clearance or evidence of
adverse drug reactions or interactions.
Develop a plan to provide symptomatic care of complications
associated with AKI, such as diuretic therapy to treat volume overload.
Monitor the patient’s weight, urine output, electrolytes (such as potassium),
and blood pressure to assess efficacy of the diuretic regimen.
Outcome Evaluation
 Goals of therapy are:
 to maintain a state of
euvolemia with good urine
output (at least 1 ml/kg per
hour),
 to return serum creatinine
and BUN to baseline,
 to correct electrolyte and
acid-base abnormalities.
 Vital signs, weight, fluid
intake, urine output, BUN,
creatinine, and electrolytes
should be assessed daily in the
unstable patient.
Dosing Drugs in AKI
 there are no published guidelines on what to do
 most important: fix reason for renal function change
 can hold every other dose of some drugs if renal function rapidly
deteriorating
 for vital drugs, you may need to adjust dose based on drug serum
concentrations
 Can use Bennett’s tables (http://www.kdpbaptist.louisville.edu/renalbook/) and pharmacokinetic
calculations for narrow therapeutic range drugs, but be aware that
renal function will be changing rapidly, so qOd or even qd
monitoring of SCr, UO, and weight will be necessary. Avoid the
most potent nephrotoxins if possible.
 Consider metabolically cleared drugs with inactive metabolites at
these times.
Prevention of AKI
Prevention of AKI
 The goals of AKI prevention are to
(a)
screen and identify patients at risk,
(b) monitor high-risk patients until the risk has subsided,
(c) implement prevention strategies when appropriate
 The preventive strategy will depend on the type of renal insult.
 Complete avoidance of all potential causes of injury is the most effective preventive
method; however, it may not always be possible to implement.
 Sometimes, the risk of renal injury is predictable, such as decreased perfusion secondary
to coronary bypass surgery or secondary to the administration of a radiocontrast dye
prior to a diagnostic procedure. In these situations, the potential insult to the kidneys
cannot be avoided but may be preventable with aggressive hydration and removal
of any additional insults.
 Patients should receive counseling regarding their optimal daily fluid intake (˜2 L/day) to
avoid dehydration, especially if they are to receive a potentially nephrotoxic medication.
 In the inpatient setting, adequate hydration, standardized hemodynamic support in the
critically ill, and avoidance of nephrotoxic medications are commonly recommended
strategies for the prevention of AKI.
Prevention of AKI
 Nonpharmacologic Therapy
 Several nonpharmacologic therapies have been explored for the prevention of AKI, including
hydration and RRT
 Pharmacologic Therapy
 Several pharmacologic therapies have been investigated for the prevention of AKI with variable
results
Prevention of AKI
 The best preventive measure for AKI, especially in individuals at high risk, is
to avoid medications that are known to precipitate AKI.
 Nephrotoxicity is a significant side effect of aminoglycosides, angiotensin-
converting enzyme inhibitors, angiotensin receptor antagonists, amphotericin B,
nonsteroidal anti-inflammatory drugs, cyclosporine, tacrolimus, and
radiographic contrast agents.
 Unfortunately, an effective, non-nephrotoxic alternative may not always be
appropriate for a given patient and the risks and benefits of selecting a
drug with nephrotoxic potential must be considered.
 For example, serious gram-negative infections may require double antibiotic
coverage, and based on culture and sensitivity reports, aminoglycoside therapy
may be necessary. In cases such as this, other measures to reduce the risk of AKI
should be instituted.
 Thus, identifying patients at high risk for development of AKI and
implementing preventive methods to decrease its occurrence or severity
is critical.