Acute Kidney Injury in

the Intensive Care

Unit

Outline

A Paradigm Shift: ARF to AKI

Consensus Definition of AKI
Functional vs Structural Biomarkers
Risk Assessment
Prevention and Intervention Therapy
Future: The Way Forward

A Paradigm Shift
Acute Renal Failure Versus Acute Kidney Injury
Function Versus Injury
Acute MyocardiaI Infarction (AMI)
Markers of function: EF
Markers of injury: troponins

In Acute Kidney Injury (AKI)

Markers of function: Creatinine
Markers of injury: No gold standard

AKI Definition
Prior to 2004: > 35 different definitions for
AKI, comparisons between studies difficult
Current consensus guidelines
ADQI (2004): RIFLE criteria (Bellomo Crit Care 2004,8:R204-12)
AKIN (2007): AKIN criteria (Mehta Crit Care 2007,11:R31)
KDIGO (2012) (KDIGO KI Supp 2012,2:19-36)

RIFLE
Creatinine Criteria

Risk
Injury

Failure
Loss
ESRD

Increased Cr
x 1.5
Increased Cr
x2
Increased Cr
x 3 or
Cr 352 umol/l

Urine Output Criteria

UO < 0.5ml/kg/h
x 6 hr

High
Sensitivity

UO < 0.5ml/kg/h
x 12 hr
UO < 0.3ml/kg/h
x 24 hr or
Anuria x 12 hrs

High
Specificity

Persistent ARF = complete loss

of renal function > 4 weeks
End Stage Renal
Disease
Bellomo Crit Care 2004,8:R204-12

Chertow et al. J Am Soc Nephrol 16:

33653370, 2005

Lassnigg et al. J Am Soc Nephrol 15:

15971605, 2004

AKIN Definition
48 hour window

Stage
R 1(I)

Stage
2
I (II)

F (III)3
Stage

Increased Cr x 1.5
or > 26.4 umol/l

UO < 0.5ml/kg/h
x 6 hr
UO < 0.5ml/kg/h
x 12 hr

Increased Cr
x2
Increase Cr
x 3 or
Cr 352 umol/l

UO < 0.3ml/kg/h
x 24 hr or
Anuria x 12 hrs

RRT Started
Mehta Crit Care 2007,11:R31

Table from Pickering, Ralib, Nejat et al. Clin. Invest. (2011) 1(5), 637650

KDIGO KI Supp 2012,2:19-36)

Urine Output Criteria For AKI

Consensus opinions amongst experts
AKI severity

AKI by urine output

AKI definition

< 0.5 ml/kg/h 6 h

Risk/Stage 1

< 0.5 ml/kg/h 6 h

Injury/Stage 2

< 0.5 ml/kg/h 12 h

Failure/Stage 3

< 0.3 ml/kg/h 24 h or

Anuria for 12 h

Ralib, Pickering, Shaw.

Critical Care. (2013)
17:R112

Mehta, R. L. Nat. Rev. Nephrol. (2013)

Functional vs Structural Injury

Biomarkers
Functional
Plasma Creatinine, Urine Output & GFR
Plasma Cystatin C

Structural
Tubular enzymes: AP, GGT, - & -GST
NGAL, urinary CysC, KIM-1, IL-18

Endre, Pickering & Walker (2011) AJP - Renal Physiology,

301(4), F697707

Murray, Mehta. Kidney International (2013)

Murray, Mehta. Kidney International (2013)

Ralib, Pickering, Shaw (2014). Manuscript submitted to Critical Care

Ralib, Pickering, Shaw (2012). J Am Soc of Nephrol,

23(2), 322333

Combination of functional and

structural biomarkers

Murray, Mehta. Kidney International (2013)

Murray, Mehta. Kidney International (2013)

Risk Assessment
Risk stratification of patients according to
susceptibilities and exposures
Manage accordingly to reduce the risk of AKI.

Monitor patients at increased risk for AKI

Individualize frequency and duration of
monitoring based on patient risk and clinical
course.

KDIGO KI Supp 2012,2:19-36)

AKI Cause and Susceptibility

Exposure

Susceptibility

Sepsis

Dehydration or Volume Depletion

Critical Illness

Advanced Age

Circulatory Shock

Female Gender

Burns

Black Race

Trauma

CKD

Cardiac Surgery (especially with CPB)

Chronic diseases (heart, lung, liver)

Major non-cardiac surgery

Diabetes mellitus

Nephrotoxic Drugs

Cancer

Radiocontrast Agents

Anaemia

Poisonous Plants and Animals

Prevention and Treatment

Monitor to stage AKI severity
Manage according to severity stage
Stage-based management of AKI

KDIGO KI Supp 2012,2:19-36)

High Risk

AKI Stage

Discontinue all nephrotoxic agents when possible

Ensure volume status and perfusion pressure
Consider functional hemodynamic monitoring
Monitor Serum creatinine and urine output
Avoid hyperglycemia
Consider alternatives to radiocontrast procedures
Non-invasive diagnostic workup
Consider invasive diagnostic workup
Check for changes in drug dosing
Consider Renal Replacement Therapy
Consider ICU admission
Avoid subclavian catheters if possible

Stage-Based Management of AKI

Endre
&
Pickering
2010

Prevention and Intervention Therapy

Pharmacological Prevention and

Intervention in AKI
Doesnt Work Further
RCTs NOT recommended

Might Work RCTs

Recommended

Works Use Suggested in

at risk patients*

Low Dose Dopamine

ANP

Isotonic Crystalloids

Diuretics

Fenoldopam

NAC for CI-AKI Prevention

IGF-1

EPO

Isotonic Saline or
Bicarbonate (for CI-AKI
Prevention)

A1-Adenosine receptor
antagonists

Theophylline x1 (for
neonates with asphyxia for
AKI prevention)

Goal Directed Therapy for

early intervention or
prevention

Further RCTs recommended. NB all drugs recommended are investigational

and not FDA approved in AKI prevention or treatment

The Future: The Way

Forward
AKI Biomarkers
Will drive understanding of the pathophysiology of
AKI
Function vs Injury

Will assist in AKI clinical trials of therapeutic

intervention
Triaging for AKI clinical trials
Outcome measures

Will facilitate risk stratification, diagnosis and

intervention

Conclusions
AKI complicates 30 to 40% of ICU patients, is
associated with increased mortality and
morbidity.
Standardised definition allow for comparison
between studies.
Early identification would enable
implementation of appropriate strategies to
prevent and treat AKI.

Bones can break, muscles can atrophy,

glands can loaf, even the brains can go
to
sleep,
without
immediately
endangering our survival; but should the
kidneys fail neither bone, muscle, gland
nor brain could carry on.
f