Prevention of Contrast AKI presented at CAMRT 2015 in Montreal (http://www.jointcongress.ca/)

1. May 28 – 30, 2015, Montréal, Québec
Contrast Nephropathy
Swapnil Hiremath, MD, MPH
@hswapnil
Nephrologist
The Ottawa Hospital
University of Ottawa
Ottawa Hospital Research Institute

2. May 28 – 30, 2015, Montréal, Québec
Disclosure Statement: With a Conflict of Interest
Financial:
• Study funding: GE Healthcare is funding an economic analysis to study the
impact of osmolality of contrast medium and acute kidney injury
• I own no stock or securities nor do I serve or have served as a consultant
for any drug or device manufacturer
Others:
• I am the PI of an ongoing trial examining oral hydration (vs IV) to prevent
contrast nephropathy
• I am a co-author of the Canadian Association of Radiology (CAR)
guidelines

3. CAMRT joint Congress May 2015
Objectives
At the end of this talk, the listener will
• Identify patients who are at high risk of contrast
nephropathy
• Know what to order to minimize risk of
contrast nephropathy

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What is Contrast
Nephropathy*?
*Now known as
Contrast-induced
Acute Kidney Injury
Following Contrast
exposure:
Arterial (cardiac cath,
arteriograms)
Venous (CT Scans)

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What is Contrast
Nephropathy*?
• Acute Kidney Injury,
defined as:
• Rise in creatinine of
25%
• Rise in creatinine of
44 micromol/L
• A much smaller
proportion: Dialysis
or Death
*Now known as
Contrast-induced
Acute Kidney Injury
Following Contrast
exposure:
Arterial (cardiac cath,
arteriograms)
Venous (CT Scans)

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Case

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Case
• 59 year old gentleman, DM2
• Worsening angina
• Cr 170 at baseline (eGFR 38)

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Case
• 59 year old gentleman, DM2
• Worsening angina
• Cr 170 at baseline (eGFR 38)

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Case
• 59 year old gentleman, DM2
• Worsening angina
• Cr 170 at baseline (eGFR 38)

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Pathophysiology
from: cJASN Jan 2008

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Pathophysiology
from: cJASN Jan 2008

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Pathophysiology
• Courtesy Prof Persson, Berlin

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Which patients are at risk?

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Which patients are at risk?
• Arterial contrast (Cardiac Catheterization,
Angiograms) >>Venous Contrast (Contrast
enhanced CT scans)

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Which patients are at risk?
• Arterial contrast (Cardiac Catheterization,
Angiograms) >>Venous Contrast (Contrast
enhanced CT scans)
• Diabetes, Dehydration

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Which patients are at risk?
• Arterial contrast (Cardiac Catheterization,
Angiograms) >>Venous Contrast (Contrast
enhanced CT scans)
• Diabetes, Dehydration
• Severe Chronic Kidney Disease (eGFR <
30, stage 4 and 5 CKD)

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How should we prevent Contrast - AKI?
Literature Roundup
>8000 publications
14 + 57 + 22 + 18
=113 RCTs
(4 interventions)
3412 with RCT
filter
42 Meta-
analyses

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How should we prevent Contrast - AKI?
Literature Roundup
>8000 publications
14 + 57 + 22 + 18
=113 RCTs
(4 interventions)
3412 with RCT
filter
42 Meta-
analyses
+ 82 studies
currently recruiting
(per
Clinicaltrials.gov)

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N-Acetyl Cysteine
(mucomyst)

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N-Acetyl Cysteine:
Mixed Evidence?
Gonzales et al, BMC Medicine, 2007

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N-Acetyl Cysteine:
Mixed Evidence?
Gonzales et al, BMC Medicine, 2007

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N-Acetyl Cysteine:
Mixed Evidence?
Gonzales et al, BMC Medicine, 2007

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N-Acetyl Cysteine:
Definitive Evidence

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N-Acetyl Cysteine:
Definitive Evidence

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N-Acetyl Cysteine:
Definitive Evidence
ACT study, Berwanger et al,
Circulation, 2011
N = 2272

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N-Acetyl Cysteine:
Definitive Evidence
ACT study, Berwanger et al,
Circulation, 2011
N = 2272

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Volume Expansion: Bicarb

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Volume Expansion: Bicarb

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Volume Expansion: Bicarb
Merten et al, JAMA
2004
N = 119

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Volume Expansion: Bicarb
or Saline?

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Volume Expansion: Bicarb
or Saline?

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Volume Expansion: Bicarb
or Saline?

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Volume Expansion: Bicarb
or Saline?

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Oral hydration?
Source: Hiremath et al, PLoS One, 2013
Small number of studies
Ongoing trial at Ottawa

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Safer Contrast Media

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Safer Contrast MediaIonicity Relative
Osmolality
Osmolality
(mOsm/kg H20)
Examples
Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate,
Metrizoate,
Iodamide, Ioxithalamate
Ionic dimers Low osmolality 600 Ioxaglate
Nonionic monomers Low osmolality 500 – 700 Iopamidol,
Iohexol,
Iomeprol,
Iopentol,
Iopromide,
Ioversol,
Ioxitol,
Metrizamide
Nonionic dimers Iso-osmolal 290-320 Iodixanol,
Iotrolan

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Safer Contrast MediaIonicity Relative
Osmolality
Osmolality
(mOsm/kg H20)
Examples
Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate,
Metrizoate,
Iodamide, Ioxithalamate
Ionic dimers Low osmolality 600 Ioxaglate
Nonionic monomers Low osmolality 500 – 700 Iopamidol,
Iohexol,
Iomeprol,
Iopentol,
Iopromide,
Ioversol,
Ioxitol,
Metrizamide
Nonionic dimers Iso-osmolal 290-320 Iodixanol,
Iotrolan

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Safer Contrast MediaIonicity Relative
Osmolality
Osmolality
(mOsm/kg H20)
Examples
Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate,
Metrizoate,
Iodamide, Ioxithalamate
Ionic dimers Low osmolality 600 Ioxaglate
Nonionic monomers Low osmolality 500 – 700 Iopamidol,
Iohexol,
Iomeprol,
Iopentol,
Iopromide,
Ioversol,
Ioxitol,
Metrizamide
Nonionic dimers Iso-osmolal 290-320 Iodixanol,
Iotrolan

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Safer Contrast MediaIonicity Relative
Osmolality
Osmolality
(mOsm/kg H20)
Examples
Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate,
Metrizoate,
Iodamide, Ioxithalamate
Ionic dimers Low osmolality 600 Ioxaglate
Nonionic monomers Low osmolality 500 – 700 Iopamidol,
Iohexol,
Iomeprol,
Iopentol,
Iopromide,
Ioversol,
Ioxitol,
Metrizamide
Nonionic dimers Iso-osmolal 290-320 Iodixanol,
Iotrolan

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Safer Contrast MediaIonicity Relative
Osmolality
Osmolality
(mOsm/kg H20)
Examples
Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate,
Metrizoate,
Iodamide, Ioxithalamate
Ionic dimers Low osmolality 600 Ioxaglate
Nonionic monomers Low osmolality 500 – 700 Iopamidol,
Iohexol,
Iomeprol,
Iopentol,
Iopromide,
Ioversol,
Ioxitol,
Metrizamide
Nonionic dimers Iso-osmolal 290-320 Iodixanol,
Iotrolan

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Safer Contrast Media
• Low Osmolar >>safer then High Osmolar (Barrett
et al, Radiology 1993)
Ionicity Relative
Osmolality
Osmolality
(mOsm/kg H20)
Examples
Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate,
Metrizoate,
Iodamide, Ioxithalamate
Ionic dimers Low osmolality 600 Ioxaglate
Nonionic monomers Low osmolality 500 – 700 Iopamidol,
Iohexol,
Iomeprol,
Iopentol,
Iopromide,
Ioversol,
Ioxitol,
Metrizamide
Nonionic dimers Iso-osmolal 290-320 Iodixanol,
Iotrolan

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Safer Contrast Media
• Low Osmolar >>safer then High Osmolar (Barrett
et al, Radiology 1993)
• Iso-osmolar versus Low osmolar?
Ionicity Relative
Osmolality
Osmolality
(mOsm/kg H20)
Examples
Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate,
Metrizoate,
Iodamide, Ioxithalamate
Ionic dimers Low osmolality 600 Ioxaglate
Nonionic monomers Low osmolality 500 – 700 Iopamidol,
Iohexol,
Iomeprol,
Iopentol,
Iopromide,
Ioversol,
Ioxitol,
Metrizamide
Nonionic dimers Iso-osmolal 290-320 Iodixanol,
Iotrolan

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Use Safer Contrast media

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Use Safer Contrast media

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Use Safer Contrast media
Aspelin et al, New Engl J Med,
2003
N = 129

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Is Iodixanol truly
superior?

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Is Iodixanol truly
superior?

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Is Iodixanol truly
superior?
CARE study, Solomon et al,
Circulation, 2007
N = 414

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Is Iodixanol truly
superior?

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Is Iodixanol truly
superior?

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Meta-Analysis: LOCM
vs IsoCM

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Meta-Analysis: LOCM
vs IsoCM

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Meta-Analysis: LOCM
vs IsoCM

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Meta-Analysis: LOCM
vs IsoCM

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Iodixanol vs
Iohexol

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Iodixanol vs
Other LOCMs

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What about Dialysis to
remove contrast?

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What about Dialysis to
remove contrast?
Cruz et al,AJKD,
2007

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What about Dialysis to
remove contrast?
Cruz et al,AJKD,
2007

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What about Dialysis to
remove contrast?
Marenzi et al, New Engl J Med,
2003
N = 114
Cruz et al,AJKD,
2007

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What about Dialysis to
remove contrast?

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What about Dialysis to
remove contrast?

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What about Dialysis to
remove contrast?
Reinecke et al, Clin Res
Cardiol, 2007

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Comparison of Effect Sizes

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Comparison of Effect Sizes
Intervention First Study
Best
Study
N-Acetyl Cysteine 0.1 1.01
Bicarb-based Hydration 0.125 0.94
Dialysis after Contrast 0.1 0.90
Iso-osmolar vs low-
osmolar Contrast
0.09 1.13

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Comparison of Effect Sizes
Intervention First Study
Best
Study
N-Acetyl Cysteine 0.1 1.01
Bicarb-based Hydration 0.125 0.94
Dialysis after Contrast 0.1 0.90
Iso-osmolar vs low-
osmolar Contrast
0.09 1.13

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Comparison of Effect Sizes
Intervention First Study
Best
Study
N-Acetyl Cysteine 0.1 1.01
Bicarb-based Hydration 0.125 0.94
Dialysis after Contrast 0.1 0.90
Iso-osmolar vs low-
osmolar Contrast
0.09 1.13

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Comparison of Effect Sizes
Intervention
First
Study
Best
Study
N-Acetyl
Cysteine
0.1
NEJM
1.01
CirculationN-Acetyl
Cysteine
0.1
N = 83
1.01
N =2400
Bicarb-based
Hydration
0.125
JAMA
0.94
JAMABicarb-based
Hydration
0.125
N =119
0.94
N = 353
Dialysis after
Contrast
0.1
NEJM
0.90
CRCDialysis after
Contrast
0.1
N = 114
0.90
N = 424
Iso-osmolar
Contrast
0.09
NEJM
1.13
JACCIso-osmolar
Contrast
0.09
N = 129
1.13
N = 418

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Contrast media
DoesVenous Contrast
cause Acute Kidney
Injury?

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Contrast media Acute Kidney Injury
DoesVenous Contrast
cause Acute Kidney
Injury?

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Contrast media Acute Kidney Injury
DoesVenous Contrast
cause Acute Kidney
Injury?

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Contrast media Acute Kidney Injury
Sepsis
Cardiogenic Shock
DoesVenous Contrast
cause Acute Kidney
Injury?

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Contrast media Acute Kidney Injury
Sepsis
Cardiogenic Shock
DoesVenous Contrast
cause Acute Kidney
Injury?

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Contrast-
induced
Contrast media Acute Kidney Injury
Sepsis
Cardiogenic Shock
DoesVenous Contrast
cause Acute Kidney
Injury?

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Contrast-
associated
Contrast media Acute Kidney Injury
Sepsis
Cardiogenic Shock
DoesVenous Contrast
cause Acute Kidney
Injury?

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DoesVenous Contrast
Cause AKI?
Source: Radiology, 2014

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DoesVenous Contrast
Cause AKI?
Source: Radiology, 2014

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Others
• If hydration helps, so will stopping diuretics
• Potentially nephrotoxic medications: NSAIDs,
others
• RAS Blockade? (ACE inhibitors,Angiotensin
receptor blockers, renin inhibitors,
spironolactone)
• Statins

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Metformin and Contrast?

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Metformin and Contrast?
• Metformin is NOT nephrotoxic;
phenformin, its predecessor was banned
for causing lactic acidosis. Case reports
exist with metformin as well

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Metformin and Contrast?
• Metformin is NOT nephrotoxic;
phenformin, its predecessor was banned
for causing lactic acidosis. Case reports
exist with metformin as well
• So, if a patient is on metformin AND

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Metformin and Contrast?
• Metformin is NOT nephrotoxic;
phenformin, its predecessor was banned
for causing lactic acidosis. Case reports
exist with metformin as well
• So, if a patient is on metformin AND
• Is given contrast AND

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Metformin and Contrast?
• Metformin is NOT nephrotoxic;
phenformin, its predecessor was banned
for causing lactic acidosis. Case reports
exist with metformin as well
• So, if a patient is on metformin AND
• Is given contrast AND
• Develops severe AKI (GFR <20) AND

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Metformin and Contrast?
• Metformin is NOT nephrotoxic;
phenformin, its predecessor was banned
for causing lactic acidosis. Case reports
exist with metformin as well
• So, if a patient is on metformin AND
• Is given contrast AND
• Develops severe AKI (GFR <20) AND
• Metformin is not stopped THEN

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Metformin and Contrast?
• Metformin is NOT nephrotoxic;
phenformin, its predecessor was banned
for causing lactic acidosis. Case reports
exist with metformin as well
• So, if a patient is on metformin AND
• Is given contrast AND
• Develops severe AKI (GFR <20) AND
• Metformin is not stopped THEN
• There is a possibility of lactic acidosis

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Metformin and Contrast?
‘ The legacy of phenformin, anecdotes,
scattered case reports, product inserts
and medicolegal anxieties are more at
the heart of this issue than scientific
fact’ - Gerald Pond, Radiology, 2001

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Summary

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Summary
• Contrast procedures have become safer with
time

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Summary
• Contrast procedures have become safer with
time
• IV (eg CT scans) contrast is considerably less
harmful than IA contrast (eg cardiac cath)

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Summary
• Contrast procedures have become safer with
time
• IV (eg CT scans) contrast is considerably less
harmful than IA contrast (eg cardiac cath)
• CKD stage 4 & 5 (GFR < 30) might still be at risk
of AKI with CT Scans

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Summary
• Contrast procedures have become safer with
time
• IV (eg CT scans) contrast is considerably less
harmful than IA contrast (eg cardiac cath)
• CKD stage 4 & 5 (GFR < 30) might still be at risk
of AKI with CT Scans
• Most prophylactic measures (bicarb, NAC,
dialysis) don’t work; except for volume expansion

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Thank you
• Email:
shiremath@toh.on.ca
• Twitter: @hswapnil
• https://about.me/
swapnil.hiremath