Role of fluids in Acute Kidney Injury

Rachel Lennon

Consultant Paediatric Nephrologist

IV Fluids Study Day, Manchester 29th January 2016

Overview

• National Patient Safety Alert • AKI epidemiology • Pathophysiology

• Fluids and AKI

• Developments in AKI

– Diagnosis – Intervention

• Take home messages

Acute Kidney Injury

• Common global health care problem

• Increasing incidence

• 20% hospital admissions

• $10 billion in the USA per year

• Increased hospital stay

• Increased morbidity and mortality

• No specific therapy

2009

Systematic failings in managing AKI in adults

• Think Kidneys Campaign

• AKI Algorithm

• Electronic AKI alerts

• Patient Safety Alert

• 9th March 2015

National AKI algorithm

• NHS England

• Standardising the early identification of AKI

• AKI 1,2,3

• Paediatrics included

– scale of problem?

Serum creatinine

result exists?

Previous result

Within 0 – 365 days?

Index creatinine value

Defined as

C1

If Result within

0 – 7 days

Then:

If Result within

8 – 365 days

Then:

Find lowest

value

Define as

RV1

Calculate RV ratio

C1 / RV1

Find MEDIAN

of results

Define as

RV2

Calculate RV ratio

C1 / RV2

Is higher RV ratio

≥ 3.0?

Is higher RV ratio

≥ 2.0 and < 3.0?

Is higher RV ratio

≥ 1.5 and < 2.0?

ALERT!

?AKI 3

Alert!

?AKI 2

ALERT!

?AKI 1

Is higher RV ratio

≥ 1.5?

Has change occurred

Within 48hrs?

Is D > 26 umol/L?Report without

alert

Report without alert.

Send to authorisation Q

If creatinine has

Increased > 26 umol/L

In < 7 days.

Consider requesting

repeat If CKD

unlikely.

< RI? Flag low

Within RI? No flag

Flag High

?AKI ?CKD

Suggest

RepeatAlgorithm for detecting Acute

Kidney Injury (AKI) based on

serum creatinine changes with

time

This algorithm relates to the

NHS England patient safety

alert: NHS/PSA/D/2014/010

RI =Population

Reference Interval

(Age and sex

related if available)

RV = Reference value. Defined as:

the creatinine value with which an index

creatinine value is compared

D = difference between

current and lowest

previous result within

48hrs

YES

NO YES

YES

NO

NO

NO YES

YES

YES

YES

YES

NO

NO

NO

NO

ULRI = upper

limit of

reference

interval

Is age < 18 years?Serum creatinine

> x3 ULRI?

Serum creatinine

> 354 umol/L?

YES

YES

YES

YES

NO

NO

NO

www.england.nhs.uk

Is AKI an issue in paediatrics?

• Depends on AKI definition used in studies

• 9-fold increase since between 1980-2005 – Vachvanichsanong P, Pediatrics 2006

• PICU:

– 25% all admissions

– 82% AKI in critically ill children (ventilation, inotropes)

– 49% AKI Royal Manchester Children’s Hospital • McCaffrey J et al, Pediatric Nephrology 2015

Paediatric AKI in England 2015

• 6 month study

• 3x tertiary and 3x DGH centres

• 57,278 creatinine values

• 5325 alerts, n=1112 patients

• 66 notes reviewed

• 18% recognised AKI

62% 16%

22%

% AKI Stage

AKI 1

AKI 2

AKI 3

Aetiology

Goldstein S, Blood Purification 2012

80’s-90’s:Primary renal (eg: HUS), sepsis, burns Shift: Secondary to systemic disease or treatment

Overview

National Patient Safety Alert AKI epidemiology • Pathophysiology

• Fluids and AKI

• Developments in AKI

– Diagnosis – Intervention

• Take home messages

The filter…

The tubules…

Pathophysiology

Symons, J Pediatric Nephrology 2013

Vaidya, VS, Annu Rev Pharmacol Toxicol 2008

Cellular injury

Overview

National Patient Safety Alert AKI epidemiology Pathophysiology

• Fluids and AKI

• Developments

– Diagnosis – Intervention

• Take home messages

Fluids and AKI

Do certain fluids cause AKI?

Fluid management in AKI

Can fluids cause AKI?

• 0.9% saline most common resuscitation fluid

• Associated with AKI and increased mortality

• High chloride contributes to AKI – Hyperchloremia and metabolic acidosis – Renal vasoconstriction – Decreased glomerular GFR

• Buffered/balanced fluids less AKI • Evidence for increased AKI with colloids in sepsis

Fluid management in AKI Concepts:

1. AKI in sepsis results from reduced renal blood flow

2. Fluid resuscitation restores renal perfusion

Legrand • Haemorhagic model

• Rats bled to MAP 30mmHg resuscitated with

normal or hypertonic saline

• Crystalloid did not improve renal microvascular perfusion

• Established AKI not responsive to more fluids

Bellamo • Hyperdynamic animals have

increased renal blood flow

• Kidneys are perfused • BUT glomerular filtration

decreased

• Downstream consequences

2014

Removal Timing and rates Intermittent HD vs CVVH

Maintenance Needs (blood products/medications/nutrition) versus Excretion of volume and solutes

Resuscitation/repletion Restore end-organ perfusion Early goal directed therapy (physiological parameters)

Three phases of fluid management…

Transition between phases unclear…

• 263 Emergency Department patients

• Randomised to 6 hours-goal-directed (CVP/MAP/O2/Hct) or standard fluid therapy

• Reduced mortality (30.5% vs 46.5%) with EGDT

• AKI not assessed

• Issues with patient exclusion and sample size • Paediatric data also support EGDT for improved survival

• 1243 adult patients with AKI Pittsburgh • Protocol versus usual care • AKI: 37.6% vs 38.1% usual care AKI • No difference in AKI duration and RRT rates • No difference in complete and partial recovery from AKI • Fluid overload 8.3% vs 6.3% fluid

• Long term F/U? • AKI common but not influenced by protocol

• Cluster randomised double crossover trail (adults/ICU/New Zealand) • 2278 patients receiving IV fluids • Randomised to 0.9% or buffered crystalloid (PL-148) • Primary outcome 2-fold increase in SCr • Secondary outcome RRT/in-hospital mortality • AKI: 9.6% vs 9.2% in saline group • RRT 3.3% vs 3.4% • Death 7.6 vs 8.6% • Effect in higher risk groups not excluded

Overview

National Patient Safety Alert AKI epidemiology Pathophysiology

Fluids and AKI

• Developments

– Diagnosis – Intervention

• Take home messages

Creatinine is a late biomarker

‘Cardiac troponins’ for the kidney?

Vaidya, VS, Annu Rev Pharmacol Toxicol 2008

New AKI biomarkers

Widely tested- No single biomarker Panel Research based

De Geus H, CKJ 2012

AKI framework

Goldstein, S CJASN 2010

Interventions

• No therapeutic agent for ‘AKI’

– Many failed medicine trials

– Animal models eg: IGF1- too late

– Test drugs with a wider therapeutic window

• Prevention and treatment studies

• Improve current practice

Symons, J Pediatr Nephrol 2013

Future possibilities: Optimisation of volume status Inhibition of apoptosis Adenosine receptor antagonism Immune modulation Ischaemic preconditioning Therapeutic hypothermia Stem cell therapy

AKI trials- registered 2011

• 126 clinical trials – 118 adults, 8 in children – 65% prevention trials (timed insult)

• Many inadequately powered – need 800 per study arm

• Few use agreed criteria

• 21/22 treatment trials – based on ICU and RRT

Faubel, S CJASN 2012

RRT- Trials

• Improve current practice:

• Eg: Improved methods of anticoagulation

– Loss of circuits

• Eg: Early initiation

– Fluid overload

Other interventions

• Detection – Patient alerts

• Prevention of secondary injury

• Medicine dosing to prevent renal injury – What is the correct dose? – Nephrotoxicity/adequate treatment

• Early nephrology consult – Non-ICU based patients – Evidence it helps!

Future strategy

Goldstein, S CJASN 2010

Fluid dosing

Take home messages

• AKI is a common problem

• Respond to Safety Alerts

• Fluids – A potential cause of AKI – Type, amount, removal

• New biomarkers

• Outcome – High risk of chronic kidney disease

Acknowledgements

Rachael Barber Paediatric Intensivist Beatrice Coupes Clinical Scientist Chris Chaloner Consultant Biochemist Philip Hudnott PICU Research Nurse James McCaffrey MRC clinical fellow Stephen Playfor Paediatric Intensivist Adam Sutherland Senior Clinical Pharmacist Nick Webb Paediatric Nephrologist