Contrast-induced Acute Kidney Injury

May 28 – 30, 2015, Montréal, Québec

Contrast Nephropathy

Swapnil Hiremath, MD, MPH@hswapnilNephrologist

The Ottawa HospitalUniversity of Ottawa

Ottawa Hospital Research Institute

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

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


What is Contrast Nephropathy*?

*Now known as Contrast-induced

Acute Kidney Injury

Following Contrast exposure:

Arterial (cardiac cath, arteriograms)

Venous (CT Scans)


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)


Case


Case• 59 year old gentleman, DM2

• Worsening angina

• Cr 170 at baseline (eGFR 38)










Pathophysiology

from: cJASN Jan 2008


Pathophysiology

from: cJASN Jan 2008


Pathophysiology

• Courtesy Prof Persson, Berlin


Which patients are at risk?



• Arterial contrast (Cardiac Catheterization, Angiograms) >> Venous Contrast (Contrast enhanced CT scans)




• Diabetes, Dehydration




• Diabetes, Dehydration

• Severe Chronic Kidney Disease (eGFR < 30, stage 4 and 5 CKD)


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


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)


N-Acetyl Cysteine (mucomyst)


N-Acetyl Cysteine: Mixed Evidence?

Gonzales et al, BMC Medicine, 2007








N-Acetyl Cysteine: Definitive Evidence





ACT study, Berwanger et al, Circulation, 2011

N = 2272



ACT study, Berwanger et al, Circulation, 2011

N = 2272


Volume Expansion: Bicarb





Merten et al, JAMA 2004

N = 119


Volume Expansion: Bicarb or Saline?








Oral hydration?

Source: Hiremath et al, PLoS One, 2013Small number of studiesOngoing trial at Ottawa


Safer Contrast Media


Safer Contrast MediaIonicity Relative

OsmolalityOsmolality (mOsm/kg H20)

Examples

Ionic monomers High osmolality 1500 – 1900 Diatrizoate, Iothalamate, Metrizoate, Iodamide, Ioxithalamate

Ionic dimers Low osmolality 600 IoxaglateNonionic monomers Low osmolality 500 – 700 Iopamidol,

Iohexol,Iomeprol,Iopentol,Iopromide,Ioversol,Ioxitol,Metrizamide

Nonionic dimers Iso-osmolal 290-320 Iodixanol,Iotrolan




Examples








Examples








Examples








Examples







• Low Osmolar >>safer then High Osmolar (Barrett et al, Radiology 1993)

Ionicity Relative Osmolality

Osmolality (mOsm/kg H20)

Examples







• Low Osmolar >>safer then High Osmolar (Barrett et al, Radiology 1993)

• Iso-osmolar versus Low osmolar?

Ionicity Relative Osmolality

Osmolality (mOsm/kg H20)

Examples






Use Safer Contrast media





Aspelin et al, New Engl J Med, 2003

N = 129


Is Iodixanol truly superior?





CARE study, Solomon et al, Circulation, 2007

N = 414






Meta-Analysis: LOCM vs IsoCM








Iodixanol vs Iohexol


Iodixanol vsOther LOCMs


What about Dialysis to remove contrast?



Cruz et al, AJKD, 2007






Marenzi et al, New Engl J Med, 2003

N = 114








Reinecke et al, Clin Res Cardiol, 2007


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








0.09 1.13








0.09 1.13


Comparison of Effect SizesIntervention

First Study

Best Study

N-Acetyl Cysteine 0.1

NEJM1.01

CirculationN-Acetyl Cysteine 0.1

N = 831.01

N =2400

Bicarb-based Hydration 0.125

JAMA0.94

JAMABicarb-based Hydration 0.125

N =1190.94

N = 353

Dialysis after Contrast 0.1

NEJM0.90

CRCDialysis after Contrast 0.1

N = 1140.90

N = 424

Iso-osmolar Contrast 0.09

NEJM1.13

JACCIso-osmolar Contrast 0.09

N = 1291.13

N = 418


Contrast media

Does Venous Contrast cause Acute Kidney

Injury?


Contrast media Acute Kidney Injury


Injury?




Injury?



SepsisCardiogenic Shock


Injury?





Injury?


Contrast-induced




Injury?


Contrast-associated




Injury?


Does Venous ContrastCause AKI?

Source: Radiology, 2014


Does Venous ContrastCause AKI?

Source: Radiology, 2014


Others

• If hydration helps, so will stopping diuretics

• Potentially nephrotoxic medications: NSAIDs, others

• RAS Blockade? (ACE inhibitors, Angiotensin receptor blockers, renin inhibitors, spironolactone)

• Statins


Metformin and Contrast?


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







• Metformin is not stopped THEN

• There is a possibility of lactic acidosis


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


Summary


Summary• Contrast procedures have become safer with

time



time

• IV (eg CT scans) contrast is considerably less harmful than IA contrast (eg cardiac cath)



time


• CKD stage 4 & 5 (GFR < 30) might still be at risk of AKI with CT Scans



time


• 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


Thank you

• Email: [email protected]

• Twitter: @hswapnil

• https://about.me/swapnil.hiremath

mailto:[email protected]

mailto:[email protected]

https://about.me/swapnil.hiremath




Health & Medicine

Contrast-induced Acute Kidney Injury