Presented at CCRT Workshop , Cairo, Egypt Scribe medical events 2013 Egypt . www.scribeofegypt.com

1. Dr. Michel Helmy
Marketing Manager – Acute Therapies
South East Europe, Middle East & Africa
CRRT Workshop
AKI
Acute Kidney Injury
AKIAKI
Acute Kidney InjuryAcute Kidney Injury

2. © 2012 – Michel Helmy 2
Anatomy of the Kidney
Approximately 1,200 ml of blood or 25 % of Cardiac Output
flows through the kidney in one minute
Renal artery
and vein
Fibrous capsule Cortex
Pyramid (medulla)
Ureter
Pelvis
Deep inside the cortex and
the medulla regions are long
hairpin-like structures called
nephrons, these are the
functional urine producing
unit of the kidney

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The Nephron
The urine producing part of the kidney
Distal tubule
Collecting duct
Loop
of Henle
Peritubular
capillaries
Proximal tubule
Bowman’s
capsule
Glomerulus Afferent arteriole
(wider)
Efferent arteriole
(narrow)
There are one million Nephrons in each kidney
The efferent arteriole, which
is narrower than the afferent
arteriole, creating a
hydrostatic pressure in
glomerulus

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Renal Function
Secretion of three different hormones:
SECRETORY FUNCTIONEXCRETORY FUNCTION
Renin: regulate blood pressure
Vitamin D: regulate calcium uptake
Excretion product of the kidney: urine
EPO: regulate red blood cell production
Remove excess fluid
Remove waste products
Regulate acid/base balance
Regulate electrolyte levels
Urea & Creatinine

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ARF… Definition .
• Definition:
• A clinical syndrome characterized by rapid reduction in renal excretory function
underpinned by variety of causes.
Serum creatinine & urine output should continue to be viewed as the best existing
markers for AKI
• Acute kidney injury causes are generally divided into
• Pre-renal
• Renal (intrinsic)
• Post-renal
relative incidence of each of these is dependent on age, gender and clinical setting.
• Glomerular Filtration Rate is reduced ….decreased urine excretion
• Nitrogenous wastes accumulates in the body (uremia)
• Metabolic & electrolytes disturbances

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Definition: AKI = ARF?
ARF = Acute Renal FailureAKI = Acute Kidney Injury
Intended to describe the
entire spectrum of disease
from being relatively mild to
severe.
Defined as renal function
inadequate to clear the waste
products of metabolism
despite the absence of
correction of hemodynamic or
mechanical causes.
Clinical manifestations of renal failure
include the following:
•Uremic symptoms (drowsiness,
nausea, hiccough, twitching)
•Hyperkalemia
•Hyponatremia
•Metabolic acidosis
Defined as an abrupt change in
serum creatinine and/or urine
output and classified according
the RIFLE criteria

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Definition of AKI
2.1.1:2.1.1:
Acute kidney injury (AKI) is defined as any of the following
(Not Graded):
• Increase in SCr by ≥ 0.3 mg/dl (≥ 26.5 µmol/l) within 48 hours;
OROR
• Increase in SCr to ≥ 1.5 times baseline, which is known or
presumed to have occurred within prior 7 days
OROR
• Urine volume <0.5 ml/kg/h for 6 hours

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Conclusion: AKI is not ARF
As you have seen, the terms acute kidney injury (AKI) and acute renal
failure (ARF) are not synonymous.
While the term renal failure is best reserved for patients who have lost
renal function to the point that life can no longer be sustained without
intervention, AKI is used to describe the milder as well as severe forms
of acute renal dysfunction in patients.
Let us have a deeper look at the classification of AKI…

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Diagnosis ARF
If the cause of ARF is not apparent, a large amount of blood tests and
examination of a urine specimen is typically performed.
• Urea in blood
• Creatinine in blood
• Urine analysis
• Urine volume output
• Ultrasound of kidneys
Conventional Units < 1.5 mg 10 - 20 mg/dl
International Units 50 - 100 μmol /L 2.6 - 6.8 mmol /L
Normal adult blood values Creatinine BUN (Blood Urea Nitrogen)
Acute Renal Failure

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Diagnosis AKI
If the cause of ARF is not apparent, a large amount of blood tests and
examination of a urine specimen is typically performed.
• Urea in blood
• Creatinine in blood
• Urine analysis
• Urine volume output
• Ultrasound of kidneys
Normal adult blood values Conventional Units International Units
Creatinine < 1.5 mg 50 - 100 μmol /L
BUN (Blood Urea Nitrogen) 10 -20 mg 2.6 - 6.8 mmol /L
Creatinine Clearance 90 – 130 16 -26 mg/kg/24 hrs
GFR 120 ml/min 180 L/day

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AKI … in the ICUs .
• An estimated 5–20% of critically ill patients experience an episode of AKI during the
course of their illness
• AKI requiring RRT has been reported in 4·9% of all admissions to intensive-care units(10)
• Data from the Intensive Care National Audit Research Centre suggests that AKI accounts
for nearly 10% of all ICU bed days (11).
• AKI is common in hospitalized patients and also has a poor prognosis.
• Non-ICU AKI, in which the kidney is usually the only failed organ, carries a mortality rate of up to
10% (12,13).
• ICU AKI is often associated with sepsis and with non-renal organ system failure (14), with
mortality rates of over 50%. These rates rise to 80% when RRT is required (15). Predictably,
death rates increase with an increasing number of failing organ systems but over 65% of survivors
recover renal function and discontinue RRT(1).
• AKI in ICUs is often only one facet of MOF, and frequently results from systemic
inflammatory reaction or sepsis.

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Incidence ARF Study
• Close to 30.000 patients were studied
• Sept. 2000 to December 2001
• 54 hospitals in 23 countries
Conclusion:
The period prevalence of ARF requiring RRT i
between 5% -
Hospital m
JAMA
n ICU was
6 % and was associated with high
ortality rate.
2005; 294:813-818

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Incidence of ARF Publication
This article states:
Acute renal failure complicates the course of
7 - 23 % of patients in the Intensive Care Unit
Referring to publications 1 -4 in the reference list
Intensive Care in Nephrology (Taylor & Francis Group - 2005) Pages 99-111

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Incidence of ARF in US. Publication
This publication states:
The annual incidence of community-acquired ARF is
approximately 100 case per 1 m
diagnosed in only 1% o sentation.
On the other hand, hospital-acqu any
as 4% of hospital ad
ad
Published on
illion population, and it is
f hospital admissions at pre
ired ARF occurs in as m
missions and 20% of critical care
missions
www.emedicine.com
Author: Richard Sinert, DO A
Professor of M
Coauthor(s): Peter R. Peacock,
University of New York Health
ssociate Professor of Emergency Medicine, Clinical Assistant
edicine, State University of New York College of Medicine;
Jr, MD Assistant Professor of Emergency Medicine, State
Sciences Center at Brooklyn,

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Traditional classification of ARF
Pre-renal ARF Post-renal ARFIntrinsic-renal ARF
The causes of ARF are traditionally divided into three categories.
Although this division is useful for classification, all three categories
may occur simultaneously in a given patient. ARF is a complication that
can occur following any medical condition. It can result from pre-renal
causes, intrinsic renal causes or post-renal causes.
Acute Renal Failure

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Pre-renal ARF
Kidney hypoperfusion (reduced blood supply) results in both
renal ischemia (reduced supply of oxygenated blood) and
low GFR
By far the most commonly type of ARF seen in ICU
Common causes:
• intravascular volume depletion
dehydration, hemorrhage
• decreased cardiac output
congestive heart failure, infarct
• systemic vasodilatation
(dilation of blood vessels)
anaphylactic shock, sepsis
Acute Renal Failure

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Intrinsic ARF
Possible causes:
• miscellaneous renal diseases
• toxins
Necrosis (is Greek for dead) = death of cell and living tissue
Tubule is part of the Nephron, the urine forming part of the kidney
Acute Renal Failure
Intrinsic renal causes account for
35-40% of ARF cases.
The causes of intrinsic renal failure
are diseases or toxins causing
damage of the small renal vessels
and glomeruli, commonly resulting
in acute tubular necrosis.

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Post-renal ARF
Increased pressure on the Bowman’s capsule offers a
resistance to normal filtration pressure, which causes an
acute reduction in GFR
Cause:
acute obstruction of the flow of
urine
Acute Renal Failure
Post-renal causes account only for about 5% of
ARF cases. They are associated with acute
obstruction of the flow of urine which can occur
at any point in the urinary tract. The obstruction
creates a back flow of urine in the kidney which
results in an increased pressure on The Bowman’s
capsule. The constant pressure offers a resistance
to the normal filtration pressure, which causes an
acute reduction in GRF.

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Causes of AKI
Volume-responsive AKI
Postoperative AKIHypotension
Sepsis-induced AKI
AKI is common in the critically ill, especially in patients with sepsis and other forms of
systemic inflammation (e.g. major surgery, trauma, burns), but other causes must be
considered. Let us look at the 4 most common causes first:
Now let’s go back to the concept of AKI!

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• ADQI (Acute Dialysis Quality Initiative) is a process initiated by a group of
physicians from different parts of the world, with the objective to seek
consensus and evidence and establish guidelines towards AKI.
• They have proposed the RIFLE classification as a definition of AKI. RIFLE
defines three grades of severity of ARF on the basis of either an acute
increase in serum creatinine, decrease in GFR or decreased urine output.
•• ClassificationClassification
•• RRiskisk
•• IInjurynjury
•• FFailureailure
Outcome:Outcome:
•• LLossoss
•• EEndnd--stage renal diseasestage renal disease
AKI … Stages (RIFLE Criteria) .

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Classification of AKI according to RIFLE criteriaRIFLE criteria
RIFLE defines three grades of
severity of AKI on the basis of
either:
• acute increase in serum
creatinine
• decrease in GFR
• decreased urine output.
Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004
Gambro Acute Therapies supports the RIFLE definition of AKI

22. 22
Staging of AKI
2.1.2:2.1.2:
AKI is staged for severity according to the
following criteria (below). (Not Graded)
Stage Serum Creatinine Urine Output
1 1.5-1.9 times baseline OR
≥0.3 mg/dl (≥ 26.5 µmol/l) increase
<0.5 ml/kg/h for 6-12
hours
2 2.0-2.9 times baseline <0.5 ml/kg/h for ≥12
hours
3 3.0 times baseline OR increase in serum creatinine
to ≥4.0 mg/dl (≥ 353.6 µmol/l) OR initiation of renal
replacement therapy OR, in patients <18 years,
decrease in eGFR to <35 ml/min per 1.73 m2
<0.3 ml/kg/h for ≥ 24
hours OR Anuria for ≥
12 hours

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RIFLE criteria: Urine Output
• Approximately 50-60% of AKI cases are non-oliguric
• Patients may continue to make urine despite an inadequate glomerular
filtration
• Although prognosis is often better if urine output is maintained, use of
diuretics to promote urine output does not seem to improve outcome (and
some studies even suggests harm)
Anuria: <100 ml/24 hour
Oliguria: 100-400 ml/24 hour
Nonoliguria: >400 ml/24 hour
Definition
Now when do we talk of ‘Oliguria’? And when is a patient ‘non-oliguric’?

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Initial treatment of AKI
Focused on fluid management
1. Hypovolemia potentiates and exacerbates all forms of ARF
2. Reversal of hypovolemia by rapid fluid infusion can be sufficient to
treat many forms of ARF
3. Rapid fluid infusion can result in life-threatening fluid overload
4. Urinary Catheter for measurement of Urine Output
5. Section 3 of the KDIGO Guideline addresses approaches to prevent
progression of AKI. An important recommendation supported by 1B
evidence is not to use diuretics to prevent AKInot to use diuretics to prevent AKI. This continues to be
a first line therapy used by many physicians upon suspicion of AKI.
Challenging fluid management problems
2- Renal Replacement Therapy in AKI

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Classification of RRT
RRT Dialysis Modalities
Intermittent Continuous
IHD SLEDD / EDD PD CRRT
PD is an intra-corporeal (inside the body) treatment all other modalities
are extra-corporeal (outside the body) treatments

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Continuous renal replacement therapy (CRRT) has become the preferred treatment
of acute kidney injury
CRRT has been proven to be suitable in patients with hemodynamic instability in the
intensive care setting and studies have confirmed its benefits with respect to solute and
fluid removal.
History of AKI Management .
CRRT
5%
peritoneal
dialysis
5%
intermittent
hemodialysis
90%
CRRT
27%
intermittent
hemodialysis
73%
late 90’s
IHD
10 to 20%
CRRT
80 to 90%
3rd MillenniumARF in the ICUARF in the ICU mid 80’s

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Outcomes of AKI
Outcomes (or endpoints) regarding AKI can either be defined as a
measurement (i.e. serum creatinine) or an event (i.e. death or need for
dialysis).
Some of these endpoints are:
Survival / Mortality
Recovery of Renal Function
Economic Analysis
Morbidity
Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004
Can be defined as lack of need for Renal
Replacement Therapy. Therefore it is important
to know when a kidney has recovered completely
or partial.
Let us see how this works!

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Renal Recovery: How to define?
Complete recovery:
Return to near baseline GFR
Partial recovery:
Failure to return to baseline
but without the need for chronic
renal replacement
Complete Renal Recovery is defined when:
Serum Creatinine (SCrt) is not more than 50% increased from baseline
example: if baseline SCrt is 1 mg/dL (88 mmol/L) complete recovery is said
to occur if the new steady state SCrt is <1.5 mg/dL (133 mmol/L)
Partial Renal Recovery is defined when:
The above condition for complete recovery is not met but the patient does
not require chronic dialysis (i.e. renal ‘loss’ has not occurred)
Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004