ACUTE KIDNEY INJURY
(AKI)
Abdirahman Nour
MMED
Internal Medicine
2/12/15
Acute kidney injury (AKI)
Definition
sudden impairment of kidney function
resulting in the retention of nitrogenous
and other waste products
a designation for a heterogeneous group
of conditions sharing common diagnostic
features (increased (BUN) concentration
(SCr))
often associated with a reduction in urine
volume
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Acute kidney injury (AKI)
Absolute increase in the serum creatinine
concentration of 0.3 mg/dL (26.4
micromol/L) from baseline
50% increase in the serum creatinine
concentration
oliguria 0.5 mL/kg per hour for more
than six hours
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Etiology and pathophysiology
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Azotemia /uremia
Definitions
Asymptomatic increase in serum urea
and Cr
Usually caused by inability of the kidney
to excrete urea, Cr and other nitrogencontaining compounds in the blood
Uremia: azotemia associated with
symptoms of kidney failure (e.g.
anorexia, nausea, itch, confusion)
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AKI: Epidemiology
AKI
Complicates 57% of acute care hospital
admissions.
Up to 30% of admissions to ICU.
Major medical complication in the
developing world, particularly in the setting
of diarrheal illnesses, infectious diseases
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AKI in the developing
world
Etiologies for AKI are region specific such
as
Envenomations from
Infectious causes
snakes, spiders, and bees;
such as malaria
Crush injuries and resultant
rhabdomyolysis from earthquakes.
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Prerenal AKI
It is the designation for a rise in SCr or
BUN concentration due to
Inadequate renal plasma flow and
intraglomerular hydrostatic pressure to
support normal glomerular filtration.
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Prerenal AKI
Volume depletion: poor po intake, vomiting,
diarrhea, diuretics, third-spacing
Hypotension: sepsis, drugs, bleeding, maybe
liver disease?
Decreased cardiac output: CHF, acute MI
Poor arterial perfusion: renal artery stenosis,
embolism, thrombosis
Often multifactorial, with meds exacerbating
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Prerenal AKI
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Prerenal AKI
Prerenal azotemia involves no
parenchymal damage to the kidney
is rapidly reversible once intraglomerular
hemodynamics are restored
Prerenal azotemia may coexist with
other forms of intrinsic AKI.
Prolonged periods of prerenal azotemia
may lead to ischemic injury, often
termed acute tubular necrosis,
or ATN
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Compensatory renal physiologic
changes
Mediators of this response include
angiotensin II, norepinephrine, and
vasopressin (ADH)
Glomerular filtration can be maintained
despite reduced renal blood flow by
angiotensin IImediated renal efferent
vasoconstriction, which maintains
glomerular capillary hydrostatic pressure
closer to normal
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Compensatory renal physiologic
changes
Myogenic reflex within the afferent arteriole
leads to dilation in the setting of low
perfusion.
Intrarenal biosynthesis of vasodilator
prostaglandins
(prostacyclin, prostaglandin E), nitric oxide
(NO) also increase in response to low renal
perfusion pressure.
tubuloglomerular feedback elicit dilation of
the juxtaposed afferent arteriole
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Compensatory renal physiologic
changes
Counterregulatory mechanisms to
maintain GFR in the face of systemic
hypotension have limits
Renal autoregulation usually fails once
the systolic blood pressure falls below 80
mmHg
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Risk factors for prerenal azotemai
HTN
Atherosclerosis
Age
Renovascular diseases
Drugs (NSAIDs,)
ACE inhibitors/ARBs
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Intrinsic AKI
The most common causes are
Sepsis
Ischemia
Nephrotoxins, both endogenous and exogenous
Conceptualize others anatomically according to
the major site of renal Parenchymal damage
Glomeruli,
Tubulointerstitium,
Vessels
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Intrinsic AKI
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SEPSIS-ASSOCIATED AKI
complicates more than 50% of cases of
severe sepsis, and greatly increases the
risk of death.
Sepsis is also a very important cause of
AKI in the developing world.
most cases of severe AKI typically occur
in the setting of hemodynamic collapse
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SEPSIS-ASSOCIATED
AKI
The hemodynamic effects of sepsis:
Vasodilatation (cytokines/induced NO)
The operative mechanisms may be
o excessive efferent arteriole vasodilation
o renal vasoconstriction
o endothelial damage( microvascular
thrombosis activation of reactive oxygen
species, and leukocyte adhesion and
migration)
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ISCHEMIAASSOCIATED AKI
kidneys receive 20% of the cardiac output and
account for 10% of resting oxygen consumption,
despite constituting only 0.5% of the human body
mass
kidneys are also the site of one of the most hypoxic
regions in the body, the renal medulla
leukocyte-endothelial interactions in the small vessels
lead to inflammation and reduced local blood flow to
the metabolically very active S3 segment of the
proximal
Tubule.
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ISCHEMIA-ASSOCIATED
AKI
Prerenal azotemia and ischemiaassociated AKI
represent a continuum of the
manifestations of renal
Hypoperfusion.
Persistent preglomerular
vasoconstriction may be a common
underlying cause of the reduction in GFR
seen in AKI
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ISCHEMIA-ASSOCIATED
AKI
implicated factors for vasoconstriction
include activation of tubuloglomerular
feedback
Increased basal vascular tone
reactivity to vasoconstrictive agents
Decreased vasodilator responsiveness
Other factors
backleak of filtrate across ischemic and
tubular epithelium and mechanical obstruction of
tubules from necrotic debris
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NEPHROTOXINASSOCIATED AKI
All structures of the kidney are
vulnerable to toxic
injury, including the tubules, interstitium,
vasculature,
and collecting system
Risk factors for nephrotoxicity include
older age
Chronic kidney disease (CKD)
prerenal azotemia
Hypoalbuminemia
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NEPHROTOXINASSOCIATED AKI
Nephrotoxins
Contrast agents
Antibiotics
Chemotherapeutic agents
Endogenous substances
(myoglobin, hemoglobin, uric acid, and
myeloma light chains)
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Drugs that contribute to acute kidney injury
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POSTRENAL ACUTE KIDNEY INJURY
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POSTRENAL ACUTE KIDNEY INJURY
The
pathophysiology
of postrenal AKI
involves
hemodynamic
alterations
triggered by an
abrupt increase
in intratubular
pressures
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Initial diagnostic work-up
The distinction between AKI and chronic kidney
disease is important for proper diagnosis and
treatment.
Easy if recent baseline SCr concentration is available
clues suggestive of CKD
radiologic studies
(e.g., small, shrunken kidneys with cortical thinning
on renal ultrasound)
Labs
normocytic anemia
secondary hyperparathyroidism with
hyperphosphatemia and hypocalcemi
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Initial diagnostic work-up
No set of tests, however, can rule out
AKI superimposed on CKD since AKI is a
frequent complication in patients with
CKD
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Initial diagnostic work-up
Physical exam
Blood pressure
JVP
Orthostatics
Palpation of bladder for distention
Exam for pulmonary and/or peripheral edema
Signs of uremia (N/V, fatigue, mental status changes, asterixis, pericardial rub)
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History and Physical Examination
Careful history taking, and physical
examination often narrow the differential
diagnosis for the cause of AKI think of
prerenal in the following
Vomiting, diarrhea, glycosuria causing
polyuria, and
Medications including diuretics, NSAIDs,
ACE inhibitors, and ARBs
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U R I N A LYSI S
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PRE RENAL
urinalysis is unremarkable
no
protein
no blood
no abnormal casts
no cells
specific gravity is high
urine [Na] < 10 mEq/l
kidney is normalperfusion is not
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RENAL
nephrotic range proteinuria, hematuria, RBC/WBC
casts..
glomerulonephritis
low grade proteinuria, pyuria (eosinophiluria), WBC
casts..
AIN
low grade proteinuria, hematuria, hemegranular
and epithelial cell casts..
ATN
if urine is bland, it is very unlikely that there is intrinsic
renal damage
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POST RENAL
urinalysis also unremarkable
physical exam: distended bladder
diagnosis usually made from imaging
hydronephrosis
diuresis after foley insertion
ultrasound
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REDUCED GFR
urinalysis
normal
abnormal*
PRE RENAL
cardiac
dehydrated
vascular
HTN
clinical Dx
normal
RENAL
diabetes
GN
serology
+/- biopsy**
* proteinuria, hematuria, RBC casts
** depends on GFR and urinalysis
POST RENAL
stones
tumors
prostate
drugs
ultrasound
renal scan
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A good approach
Make sure the patient is not dry or
hypotensive
try giving some fluid
Put in a foley catheter especially if
male
Stop toxic drugs // adjust doses of drugs
diclofenac, ibuprofen, indomethacin,
gentamicin, (vancomycin)
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Approach to AKI
Investigations
blood: CBC, electrolytes, Cr, urea (think
prerenal if increase in urea is relatively
greater than increase in Cr), Ca2+ , PO
urine volume, C&S, R&M: sediment, casts,
crystals
urinary indices
Foley catheterization (rule out bladder outlet
obstruction)
fluid challenge (i.e. fluid bolus to rule out
most pre-renal causes)
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Approach to AKI
Imaging
abdo U/S (assess kidney size,
hydronephrosis, post-renal obstruction)
indications for renal biopsy
diagnosis is not certain
prerenal azotemia or ATN is unlikely
oliguria persists >4 wks
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MANAGEMENT
Disease Specific Therapies
if pre-renal improve perfusion
if post renal relieve the obstruction
if renal treat the underlying GN or AIN and support
the ATN
usually, prompt attention will quickly resolve
renal dysfunction
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MANAGEMENT
Non-Specific (Supportive) Therapies
drug management
fluid balance
electrolyte homeostasis
acid base balance
management of uremia
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FLUID BALANCE
most patients with AKI lose ability to regulate volume
status
unable
to dilute or concentrate urine
excrete fixed amount of urine daily
excrete fixed amount of sodium daily
must regulate intake or overload will occur
pulmonary
edema
similarly, if pt gets dehydrated after GFR starts to
improve, kidney function may not recover
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ELECTROLYTES
problems can occur with:
potassium
sodium
calcium
phosphorus
magnesium
major clinical problem is hyperkalemia
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Complications
Uremia
Hypervolemia/ hypovolemia
Hyponatremia
Hyperkalemia
Acidosis
Hyperphosphatemia/hypocalcemia
Bleeding
Infectiosn/cardiac complications
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OUTCOME AND PROGNOSIS
AKI
high morbidity and mortality in patients with
sustained AKI and multi-organ failure
is associated with a significantly increased
risk of in-hospital and long-term mortality
longer length of stay
increased costs
Prerenal azotemia, with the exception of the
cardiorenal and hepatorenal syndromes, and
postrenal azotemia carry a better prognosis
than most cases of intrinsic AKI2/12/15
THANKS
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