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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