AKI in the ICU setting

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

Pickering, Ralib, Nejat Clin. Invest. (2011) 1(5), 637–650

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

Risk

Injury

Failure

Loss

ESRD

Increased Cr x 1.5

End Stage Renal Disease

Creatinine Criteria Urine Output Criteria

UO < 0.3ml/kg/hx 24 hr or

Anuria x 12 hrs

UO < 0.5ml/kg/hx 12 hr


Increased Cr x 2

Increased Crx 3 or

Cr 352 umol/l

HighSensitivity

HighSpecificity

Persistent ARF = complete loss of renal function > 4 weeks

Bellomo Crit Care 2004,8:R204-12

Lassnigg et al. J Am Soc Nephrol 15: 1597–1605, 2004

Chertow et al. J Am Soc Nephrol 16: 3365–3370, 2005

R (I)

I (II)

F (III)

Increased Cr x 1.5or > 26.4 umol/l

UO < 0.3ml/kg/hx 24 hr or

Anuria x 12 hrs



Increased Cr x 2

Increase Cr x 3 or

Cr 352 umol/l

AKIN Definition

RRT Started

Mehta Crit Care 2007,11:R31

48 hour window

Stage 1

Stage 2

Stage 3

Table from Pickering, Ralib, Nejat et al. Clin. Invest. (2011) 1(5), 637–650

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, α- & π-GST– NGAL, urinary CysC, KIM-1, IL-18

Endre, Pickering & Walker (2011) AJP - Renal Physiology, 301(4), F697–707

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), 322–333

Combination of functional and structural biomarkers



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.


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


Avoid subclavian catheters if possible

High Risk

Discontinue all nephrotoxic agents when possible

Consider invasive diagnostic workup

Consider Renal Replacement Therapy

1 2 3

Non-invasive diagnostic workup

Ensure volume status and perfusion pressure

Check for changes in drug dosing

AKI Stage

Consider functional hemodynamic monitoring

Monitor Serum creatinine and urine output

Consider ICU admission

Avoid hyperglycemia

Consider alternatives to radiocontrast procedures

Stage-Based Management of AKI

Endre &Pickering 2010

Prevention and Intervention Therapy

Pharmacological Prevention and Intervention in AKI

Doesn’t 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

Documents

AKI in the ICU setting