Acute Kidney Injury in Sepsis

Ach Syaiful Ludf

Departement of Internal Medicine

Airlangga School of Medicine-dr.Soetomo
Teaching Hospital
Surabaya
2014

INTRODUCTION
Acute Kidney Injury (AKI) : the entire spectrum of the
syndrome from minor changes in markers of renal function
to requirement for Renal Replacement Therapy (RRT)
(KDIGO, 2012)

AKI in Sepsis 19% patients with moderate sepsis,

23% with severe sepsis and 51% with septic shock
Distinguishing between septic and non-septic AKI may
have clinical relevance for physicians
(Majumdar, 2010)

Pathophysiology of AKI in sepsis is not known clearly

Prevention and management important
(Rajapakse, 2009)

DEFINITION AKI
RIFLE criteria (ADQI, 2004) & AKIN criteria (AKIN, 2007)

DEFINITION AKI
Staging AKI (KDIGO, 2012)
AKI is defined as any of the following (Not Graded):
Increase in SCr by 0.3 mg/dl ( 26.5 lmol/l) within 48 hours;
or
Increase in SCr to 1.5 times baseline, which is known or
presumed to have occurred within the prior 7 days; or
Urine volume < 0.5 ml/kg/h for 6 hours.

CAUSES OF AKI

(Lattanzio, 2009; Markum, 2006)

CAUSES OF AKI
Prerenal AKI Postrenal
AKI

Renal AKI

Secondary to
underperfusio
n
renal or
extrarenal
losses
Heart failure
Cirrhosis
Sepsis.

Tubular cell injury

Ischemia and
inflammation (sepsis,
surgery)
Toxins
Interstitium
Acute interstitial
nephritis (AIN)
Glomerulus
acute
glomerulonephritis
Vasculature

Urinary tract
obstructions
Stones
tumor

(Lattanzio, 2009; Markum, 2006)

Definition AKI in Sepsis

The simultaneous presence of :
1.Criteria for AKI,
2.The consensus criteria for sepsis
3.If possible, the absence of other clear
and established, non-sepsis-related
causes of AKI (e.g., radiocontrast, other
nephrotoxins)
(Ricci, 2009).

PATHOGENESIS OF AKI IN
SEPSIS
1.Renal Hemodynamics
2.Renal Apoptosis
3.Endothelial Damage
4.Tubular Damage

Renal Hemodynamics

New study
RBF ????

Increase
or
decrease
??
(Ricci,2009; Rajapakase, 2009)

PATHOGENESIS OF AKI IN SEPSIS

PATHOGENESIS OF AKI IN SEPSIS

Renal Hemodynamics
New Hypotesis
Hyperdynamic sepsis

(Rajapakase, 2009;Kockara, 2013)

PATHOGENESIS OF AKI IN SEPSIS

Renal Apoptosis

Wan, 2003; Havasi, 2011

PATHOGENESIS OF AKI IN SEPSIS

Endothelial Damage
sepsis
IL-1b, TNF and PAF
increase the neutrophil
aggregation and toxic
substance release

Activation of coagulation system

by endotoxin, tissue
factor release, thrombocyte and
fibrin aggregation
Decrease in fibrinolytic activity,
endothelial damage

glomerular capillaries
microthrombi

(Havasi, 2011; Kockara, 2013)

PATHOGENESIS OF AKI IN SEPSIS

Tubular Damage
Necrosis or apoptosis
Tubular epithelium lose basal
membrane adhesion quality
Excreted to the tubular lumen
Tubular epithelium cylinders or
granular cylinders In urine
Microobstruction

(Kockara, 2013)

EARLY DIAGNOSIS AKI

BUN and serum creatinine are not very sensitive or
specific affected by many renal and nonrenal factors

New Biomarker
Biological marker of the inflammatory process : Cystatin C,
neutrophil gelatinase-associated lipocalin (NGAL) and
IL-18
Tubular protein : kidney injury molecule-1 (KIM-1), Urine
sodium/hydrogen exchanger isoform 3 (NHE3) and Liver
fatty acid-binding protein (L-FABP)
Biological markers of tubular disease : 1-microglobulin,
2-microglobulin, N-acetyl--D-glucosaminidase, etc
Edelstein, 2008; Parikh, 2008; Roesli, 2008

EARLY DIAGNOSIS AKI

Biomark Sampl Cardiopulmonary Contrast
Bypass (CPB)
er
e
Nephropat
Name
Sourc
hy
e

Sepsis or
ICU Setting

Kidney
Transplant
(tx)

NGAL

Urine

2 hrs post-CPB

4 hrs
48 hrs
postcontra before AKI
st

1224 hrs
post-tx

IL-18

Urine

4-6 hrs postCPB

Not tested

48 hrs
before AKI

1224 hrs
post-tx

KIM-1

Urine

12-24 hrs post- Not tested

CPB

Not tested

Not tested

NGAL

Plasm
a

2 hrs post-CPB

2 hrs
48 hrs
postcontra before AKI
st

Not tested

12 hrs postCPB

8 hrs
48 hrs
Variable
postcontra before AKI
Edelstein, 2008; Parikh, 2008; Roesli, 2008
st

Cystatin Plasm
C
a

AKI EVALUATION
AKI
Clinical evaluation and
physical examination.
Clinical Test
Lab values
AKI stage
KDIGO, 2012

Stage-based management
of AKI

KDIGO, 2012

AKI management
A.Maintain hemodynamic status
a. Status Volume Optimalization
b. Vasopressor use
c. Diuretic use
B. Avoid nephrotoxic drugs
C. Avoid nephrotoxic contrast media
D. Glycemic Control
E. Nutrition
F. Renal Replacement Therapy

A. Maintain hemodynamic status

a. Status Volume Optimalization

Ronco,2008;Majumdar,2010; KDIGO, 2012

A. Maintain hemodynamic status

b. Vasopressor use

Rajapakse,2009; Majumdar,2010; KDIGO, 2012

A. Maintain hemodynamic status

c. Diuretic use

Bagshaw, 2007; KDIGO, 2012

B. Avoid nephrotoxic drugs

KDIGO suggest not using aminoglycosides for the treatment

of infections unless no suitable, less nephrotoxic, therapeutic
alternatives are available
Perazella MA, 2012; KDIGO, 2012

C. Avoid nephrotoxic contrast

media
Assess the risk for CI-AKI
Consider alternative imaging methods in patients
at increased risk for CI-AKI
If the procedure still needed : use the lowest
possible dose of contrast medium and using
either iso-osmolar or lowosmolar iodinated
contrast media

KDIGO, 2012

D. Glycemic Control

Rajapakse,2009;Majumdar,2010; KDIGO, 2012

E. Nutrition

Ricci, 2011; KDIGO, 2012

E. Nutrition

Ricci, 2011; KDIGO, 2012

F. Renal Replacement Therapy

Two fundamental questions in severe AKI :
Whether or not to provide RRT ?
When to start RRT ?
Initiate RRT emergently when life-threatening
changes in fluid, electrolyte, and acid-base
balance exist

KDIGO, 2012; Rajapakse,2009;Majumdar,2010

F. Renal Replacement Therapy

Goals treatment of AKI with RRT :
1.To maintain fluid and electrolyte, acid-base, and
solute homeostasis.
2.To prevent further insults to the kidney
3.To permit renal recovery; and
4.To allow other supportive measures (e.g., antibiotics,
nutrition support) to proceed without limitation or
complication

Intermittent hemodialysis (IHD) or CRRT?

1. No difference in mortality
2. CRRT may be the preferred mode in very unstable patients
KDIGO, 2012; Rajapakse,2009;Majumdar,2010

CONCLUSION
AKI in Sepsis, a commonly condition in an
ICU
The patophysiology AKI in sepsis not fully
understood
A better understanding of AKI in sepsis is
required to implement prevention strategies
and appropriate therapy
Risk factors identification, evaluation and
appropriate management are important in
septic condition to prevent AKI

THANK YOU

Schematic representation of the inflammatory response to sepsis and resulting kidney injury. (Modified from205; reprinted with
permission.
Jaber BL et al: Blood Purif 22: 101111, 2004). Abbreviations are: GFR, glomerular filtration rate; NAG, N-acetyl- -D-glucosaminidase; KIM,
kidney injury molecule 1.

dopamin
At low doses (0.5-3.0 g/kg/min), dopamine acts predominantly on
D1 receptors in the renal, mesenteric, cerebral and coronary beds
resulting in selective vasodilation. Some reports suggest that
dopamine increases urine output by augmenting renal blood flow
and glomerular filtration rate and natriuresis by inhibiting
aldosterone and renal tubular transport [2]. But the clinical
significance of renal-dose dopamine is somewhat controversial
because a renal protective effect has not been demonstrated.
At intermediate doses (3-10 g/kg/min), dopamine also stimulates
1 receptor and increases cardiac output (CO), predominantly by
increasing stroke volume with variable effect on heart rate.
At higher dose (10-20 g/kg/min), the predominant effect of
dopamine is to stimulate 1-adrenergic receptors and produce
vasoconstriction with an increased systemic vascular resistance
(SVR), and the sum of these effects is an increase in mean arterial
pressure (MAP)

NE
Noradrenaline (also known as norepinephrine) is a potent 1adrenergic receptor agonist with modest -agonist activity
because of which it is incorrectly labelled as a pure vasopressor
However, it has shown effects on contractility in critical illness
[9].
It primarily increases systolic, diastolic and pulse pressure and
has a minimal net impact on CO. It has minimal chronotropic
effects because of which it is a drug of choice in settings where
heart rate stimulation is undesirable. Coronary flow is
maintained to certain extent because of its vasoconstrictor
effects [10]. Due to relative scarcity of cerebral vascular
adrenergic receptor, high doses of noradrenaline can be safely
used to maintain cerebral perfusion pressure without
significantly compromising the circulatory flow

 Dopamine increases MAP and cardiac output, primarily

due to an increase in stroke volume and heart rate.
Norepinephrine increases MAP due to its
vasoconstrictive effects, with little change in heart rate
and less increase in stroke volume compared with
dopamine.
Norepinephrine is more potent than dopamine and may
be more effective at reversing hypotension in patients
with septic shock.
Dopamine may be particularly useful in patients with
compromised systolic function but causes more
tachycardia and may be more arrhythmogenic than
norepinephrine

AIN
The mechanism of drug-induced AIN is unknown, but an
immunological basis is suspected. Drugs can elicit an
immune response leading to AIN in different ways. The
drug can bind to a normal component of the tubular
basement membrane (TBM) and act as a hapten or the
drug can mimic an antigen normally present within the
TBM or the interstitium and induce an immune response
that will also be directed against this antigen. Other ways
to evoke an immune response include the drug binding
to the TBM or deposit within the interstitium and act as a
planted (trapped) antigen. The drug can also elicit the
production of antibodies and become deposited in the
interstitium as circulating immune complexes

 HAART include crystal-induced obstruction

secondary to use of protease inhibitors
(mainly indinavir and atazanavir), and
proximal tubule damage related to the
nucleotide analog reverse transcriptase
inhibitor tenofovir. Acute kidney injury (AKI)
can occur following tenofovir-induced tubule
dysfunction or as a result of severe
mitochondrial dysfunction and lactic acidosis
induced by nucleoside reverse transcriptase
inhibitors