Contrast Media-Induced Nephropathy: What you’re DYEing to...
Transcript of Contrast Media-Induced Nephropathy: What you’re DYEing to...
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Contrast Media-Induced Nephropathy:What you’re DYEing to know about!!
Stephen M. Korbet, M.D.Professor of Medicine
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Cases
FP is a 78 yo WF with a long history of DM and HTN was admitted for evaluation of chest pain, nausea and vomiting. Her SCr was 1.0, Urinalysis- Normal.
CB is an 81 yo WM with a history of HTN, renal cell CA s/p right nephrectomy in 2002 and metastatic prostate CA was admitted for evaluation of low back pain.
His SCr was 1.2 mg/dl, urinalysis- Normal, and Renal US-L kidney 14.6 cm, no hydronephrosis.
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In both cases a contrast CT of abdomen and pelvis was performed using 125 ml of iopamidol (Isovue)
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What is the incidence of hospital acquired acute renal failure and what
are the causes?
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Hospital Acquired ARF: The Rush Experience
Nash et al. AJKD 2002
Prospective study from Feb to June 1996 (4 mo)
4,622 consecutive medical and surgical admissions
Acute renal failure during the hospitalization
ARF defined by an increase in SCr of >0.5 mg/dl
ARF developed in 332 (7%) patients
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Hospital Acquired ARF: The Rush Experience
Nash et al. AJKD 2002
(44%)(18%)(13%)
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61%
Hospital Acquired ARF: The Rush Experience
Nash et al. AJKD 2002
(25%)(36%)
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51%
Hospital Acquired ARF: The Rush Experience
Nash et al. AJKD 2002
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25%
Hospital Acquired ARF: The Rush Experience
Nash et al. AJKD 2002
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Nash et al. AJKD 2002
Hospital Acquired ARF: The Rush Experience
Cardiac cath and coronary angioplasty 21 (49%)CT scan 14 (33%)Peripheral angiogram 3 (7%)Other 5 (12%)TOTAL 43
Type of Contrast Study Resulting in ARF
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Hospital Acquired ARF: The Rush Experience
Cardiac cath and coronary angioplasty 2.8% CT scan 1.7%
Proportion of Contrast Studies Resulting in ARF(Overall, 750 Cardiac Caths and 825 CTs done in 4 mo)
Nash et al. AJKD 2002
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Contrast media-induced nephropathy
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Earl D. Osborne, MD Leonard G. Rowntree, MD
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Dermatologists at the Mayo Clinic studying the use of iodine-containing compounds in the treatment of syphilis
They recognized the value of the known radiopacity and renal excretion of iodine in rendering the urinary tract opaque to x-ray
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Jour. A.M.A.Feb 10, 1923
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• 1930, proposed using an organic nucleus as iodine carrier• Benzoic acid is metabolized to hippuran• Hippuran is excreted by the kidneys• Lead to the development of sodium diatrozoate in 1950s
Moses Swick, MD
“father of intravenous urography”
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• Sodium salt of tri-iodinated benzoic acid • Ionic with high osmolarity (>1500 mOsm/kg)• Water soluble, not protein bound, mol wt- 636• 99% excreted by glomerular filtration• Renal clearance of 50% by 30-60 minutes
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New England Journal of Medicine 1968
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Osmolarity(mOsm/kg)
Ionicity
Benzine rings
Name
Viscosity at 98.6F
Diatrizoate IopamidalIohexol
Iodixanol
High(>1500)
Low(600-1000)
Iso(280)
Ionic Nonionic Nonionic
Monomer Monomer Dimer
6 mPa.S 5-10 mPa.S 11 mPa.S
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What is the definition and presentation of contrast media-
induced nephropathy?
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Contrast media-induced nephropathy:
An increase in serum creatinine within up to 48-72 hours of a contrast procedure
Increase in serum creatinine
Absolute: 0.5 mg/dl
Relative: 25%
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• Overall incidence of ARF from contrast is 3%
• The incidence is 0.6% in patients with normal renal function
Incidence of Contrast Media-Induced Nephropathy
Rudnick et al, KI 1995
In 2010, 3.3 million Cardiac Angio & 70 million CTs0.03 x 73 = 2.2 million
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Usually non-oliguric
Contrast Media-induced Nephropathy
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Usually non-oliguric
Urinalysis has minimal or no proteinuria and bland sediment with granular casts
Contrast Media-induced Nephropathy
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Usually non-oliguric
Urinalysis has minimal or no proteinuria and bland sediment with granular casts
Fractional excretion of sodium is low
Contrast Media-induced Nephropathy
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Usually non-oliguric
Urinalysis has minimal or no proteinuria and bland sediment with granular casts
Fractional excretion of sodium is low
Serum creatinine peaks by 4 to 5 days
Contrast Media-induced Nephropathy
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5 days
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What are the proposed mechanisms forcontrast media-induced nephropathy?
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Contrast media induces CYTOTOXIC and HEMODYNAMIC insults
Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
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Contrast Media
Cellular effects
Idee et al. Invest Radiol 2004
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Contrast Media
Cellular effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Acute Renal FailureIdee et al. Invest Radiol 2004
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Hardiek et al. Am J Physiol Renal Physiol 2001
Altered Mitochondrial Function in Porcine Proximal Tubule Cell Line
Low-
Iso-
Hyper-
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Acute Renal FailureIdee et al. Invest Radiol 2004
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
Acute Renal FailureIdee et al. Invest Radiol 2004
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
Acute Renal FailureIdee et al. Invest Radiol 2004
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
vasoconstriction
Acute Renal FailureIdee et al. Invest Radiol 2004
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
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Brevis, NEJM 1995
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Liss et al. Eur J Physiol 1997
Effect of Contrast on pO2 in the Cortex
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Liss et al. Eur J Physiol 1997
Effect of Contrast on pO2 in the Outer Medulla
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Osmolarity(mOsm/kg)
Ionicity
Benzine rings
Name
Viscosity at 98.6F
Diatrizoate
High(>1500)
Ionic
Monomer
6 mPa.S
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Osmolarity(mOsm/kg)
Ionicity
Benzine rings
Name
Viscosity at 98.6F
Diatrizoate IopamidalIohexol
High(>1500)
Low(600-1000)
Ionic Nonionic
Monomer Monomer
6 mPa.S 5-10 mPa.S
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Osmolarity(mOsm/kg)
Ionicity
Benzine rings
Name
Viscosity at 98.6F
Diatrizoate IopamidalIohexol
Iodixanol
High(>1500)
Low(600-1000)
Iso(280)
Ionic Nonionic Nonionic
Monomer Monomer Dimer
6 mPa.S 5-10 mPa.S 11 mPa.S
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Effect of Contrast on pO2 in the Outer Medulla
Liss et al. KI 1998
Iso-osmolar
Low-
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Iso-osmlar compounds have greater viscosity
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
endothelin release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
endothelin release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery
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Increased In-Vivo Plasma Endothelin Levels are Not Related to Contrast Osmolarity
Solomon: KI 1998
Hyper-
Low-
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
endothelin release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery +
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What is the course and outcome incontrast media-induced nephropathy?
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Serum creatinine peaks by 4 to 5 days and returns to baseline over 7 to 10 days
Contrast Media-induced Nephropathy
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Increases length of hospital stay
Need for dialysis (10-25%)
Failure of SCr to return to baseline (30%)
Associated with increased patient mortality (34%)
Morbidity of Contrast Media-induced Nephropathy
Solomon: KI 1998
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16,248 hospitalized pts having contrast studies
Contrast induced ARF- 1.1%
ARF requiring dialysis- 12%
Mortality rate: Yes No p value
ARF 34% 7% <0.001
Dialysis 60% 31% <0.01 CMIN increased the risk of severe non-renal
causes of death (sepsis, bleeding, resp failure, delerium)
Increased Mortality Associated with Contrast Media-induced Nephropathy
Levy et al, JAMA 1996
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Hospital Acquired ARF: The Rush Experience
Nash et al. AJKD 2002
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Days
0
1
2
3
4
5
6
7
8
SC
r [m
g/d l
]
0
0.5
1
1.5
2
2.5
3
3.5
4
Urine V
ol [L/day]
FPCBFP UOCB UO
ContrastStudy
HD
5 days
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Days
0
1
2
3
4
5
6
7
8
SC
r [m
g/d l
]
0
0.5
1
1.5
2
2.5
3
3.5
4
Urine V
ol [L/day]
FPCBFP UOCB UO
ContrastStudy
HD
5 days
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Days
0
1
2
3
4
5
6
7
8
SC
r [m
g/d l
]
0
0.5
1
1.5
2
2.5
3
3.5
4
Urine V
ol [L/day]
FPCBFP UOCB UO
ContrastStudy
HD
5 days 11 days
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What are the risk factors forcontrast media-induced nephropathy?
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Risk Factor Odds ratioPatient RelatedSCr level (mg/dl):
1.2-1.9 2.42.0-2.9 7.4>3.0 12.8
Risk Factors for Contrast Nephropathy
Goldenberg & Matetzky CMAJ 2005
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Risk Factor Odds ratioPatient RelatedSCr level (mg/dl):
1.2-1.9 2.42.0-2.9 7.4>3.0 12.8
Diabetes mellitus 5.5
Risk Factors for Contrast Nephropathy
Goldenberg & Matetzky CMAJ 2005
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McCullough, Applications in Imaging 2003
Renal Function Predicts Risk of Contrast Nephropathy
0 10 20 30 40 50 60
Calculated CrCl (mL/min)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Ren
al E
vent
Rat
e
1020304050
Non-diabetic
Diabetic
Dialysis
CMIN
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Risk Factor Odds ratioPatient RelatedSCr level (mg/dl):
1.2-1.9 2.42.0-2.9 7.4>3.0 12.8
Diabetes mellitus 5.5Age (per yr increase) 1.02CHF 1.5HTN 1.2Low effective circulatory volume 1.2Myocardial infarction 1.9Intra-aortic balloon pump 1.9
Risk Factors for Contrast Nephropathy
Goldenberg & Matetzky CMAJ 2005
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Risk Factor Odds ratioPatient RelatedSCr level (mg/dl):
1.2-1.9 2.42.0-2.9 7.4>3.0 12.8
Diabetes mellitus 5.5Age (per yr increase) 1.02CHF 1.5HTN 1.2Low effective circulatory volume 1.2Myocardial infarction 1.9Intra-aortic balloon pump 1.9OtherLow vs high osmolar in CRI 0.5Volume of contrast (per 100 mL) 1.12
Risk Factors for Contrast Nephropathy
Goldenberg & Matetzky CMAJ 2005
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The increased risk in patients with DM, HTN or vascular disease may be a result of “endothelial
dysfunction” with decreased release of vasodilatory substances such as nitric oxide
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Risk Factor Integer scoreRisk factorHypotension 5Intra-aortic balloon pump 5CHF 5SCr >1.5 mg/dl 4Age >75 yrs 4Anemia 3Diabetes mellitus 3Volume of contrast (per 100 mL) 1Risk categoriesLow <5Moderate 6-10High 11-15Very High >16
Risk Assessment to Predict Contrast Nephropathy
Mehran et al, J Am Coll Cardiol 2004
ARF8%14%26%57%
HD0.04%0.1%1%13%
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Risk Factor Integer scoreRisk factorHypotension 5Intra-aortic balloon pump 5CHF 5SCr >1.5 mg/dl 4Age >75 yrs 4Anemia 3Diabetes mellitus 3Volume of contrast (per 100 mL) 1Risk categoriesLow <5Moderate 6-10High 11-15Very High >16
Risk Assessment to Predict Contrast Nephropathy
Mehran et al, J Am Coll Cardiol 2004
FP CB
4 43 331 1
811
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Risk Factor Integer scoreRisk factorHypotension 5Intra-aortic balloon pump 5CHF 5SCr >1.5 mg/dl 4Age >75 yrs 4Anemia 3Diabetes mellitus 3Volume of contrast (per 100 mL) 1Risk categoriesLow <5Moderate 6-10High 11-15Very High >16
Risk Assessment to Predict Contrast Nephropathy
Mehran et al, J Am Coll Cardiol 2004
FP CB
4 43 331 1
811
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Defining Chronic Renal Insufficiency
• Serum creatinine >1.5 mg/dl
• Calculated creatinine clearance <60 ml/min
Cockcroft and Gault equation:
140-age x kg
Scr x 72= [x .85 in women]
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(-15)
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Pt SCr CrCL
FP 1.0 54 ml/min
CB 1.2 55 ml/min
Calculated Creatinine clearances
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Risk Factor Integer scoreRisk factorHypotension 5Intra-aortic balloon pump 5CHF 5SCr >1.5 mg/dl 4Age >75 yrs 4Anemia 3Diabetes mellitus 3Volume of contrast (per 100 mL) 1Risk categoriesLow <5Moderate 6-10High 11-15Very High >16
Risk Assessment to Predict Contrast Nephropathy
Mehran et al, J Am Coll Cardiol 2004
FP CB
4 44 43 331 1
15 12
ARF8%14%26%57%
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What prophylactic measure can be taken to reduce the risk of contrast
media-induced nephropathy?
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• Delay exposure in hemodynamically unstable pts
• Avoid repeated exposure– 48 hrs in pts with normal renal function– 72 hrs in pts with CRI or DM– until SCr returns to baseline in ARF
• Discontinue NSAIDs for 1-2 days prior
Modification of Risk Factors to Prevent CMIN
Goldenbergf, CMAJ 2005
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• Contrast media• Hydration• Pharmacologic agents• Prophylactic dialysis
Prophylaxis of Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
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• Contrast media– Minimize the dose– Avoid repeated exposure– Use the least toxic form of contrast
Prophylaxis of Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
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Rudnick et al, KI 1995
Non-ionic vs Ionic Contrast Media
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Kidney International 1995
(Coronary angiography)
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Rudnick et al, KI 1995
(ARF defined by >0.5 mg/dl increase in SCr at 48-72 h)
High vs Low Osmolar Contrast Media in Cardiac Angiography
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Non-ionic Low vs Iso-OsmolarContrast Media
Aspelin et al, NEJM 2003
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• Randomized, double-blind, prospective study• 129 pts with DM and SCr of 1.5 to 3.5 mg/dl or
calculated CrCl of <60ml/min• Underwent coronary or aorto-femoral angiography• All pts were well hydrated
Non-ionic Low vs Iso-osmolar Contrast Media
Aspelin et al, NEJM 2003
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Aspelin et al, NEJM 2003 P <0.01
290 mOsm/kg
780 mOsm/kg
3%
26%
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(ARF defined by >0.5 mg/dl increase in SCr at 24-72 hrs)
DB-RC Trials of Low vs Iso-Osmolar Contrast in Pts with eGFR <60 Having Coronary Angiography
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What is the risk of CIN in CKD pts (eGFR <60) undergoing intravenous contrast enhanced CT?
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DB-RC Trials of Low vs Iso-Osmolar Contrast in CKD Pts Undergoing CT scans
Thomsen
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DB-RC Trials of Low vs Iso-Osmolar Contrast in CKD Pts Undergoing CT scans
Intra-arterial adm delivers greater concentration and/or volume.
Thomsen
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Prophylaxis of Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
• Contrast media• Hydration• Pharmacologic agents• Prophylactic dialysis
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• Increases renal blood flow and GFR in volume contracted patients
• Increases medullary blood flow, enhancing regional pO2
• Reduces concentration of contrast in tubules
Proposed Beneficial Effects of Hydration
Persson et al. KI 2005
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What is the most effective form of hydration ?
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H2O: 1 Liter
Intra-cellularExtra-cellular
330 ml 660 ml
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H2O: 1 Liter
Intra-cellularExtra-cellular
330 ml 660 ml
0.45-NS: 1 Liter 330 ml500 ml
+170 ml670 ml
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H2O: 1 Liter
Intra-cellularExtra-cellular
330 ml 660 ml
NS: 1 Liter 1000 ml
330 ml500 ml
+170 ml670 ml
0.45-NS: 1 Liter
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• Prospective, randomized trial in 53 pts• Unrestricted oral fluids vs 0.9% NS infused at 1
ml/kg/hr for 12 hrs prior to the procedure• Primary endpoint:
>0.5 mg/dl increase in SCr within 48 hrs
• Oral: 9/26 (35%) vs NS: 1/27 (3%), p <0.01
Comparison of Oral vs 0.9% Saline Hydration in Patients Undergoing Coronary Angioplasty
Trivedi et al. Nephron Clin Pract 2003
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• Prospective, randomized, controlled trial: 1,383 pts• Low-osmolar contrast• N-acetylcysteine was NOT used• 0.9% vs 0.45% NS infused at 1 ml/kg/hr for 24 hrs
• Primary endpoint:– >0.5 mg/dl increase in SCr within 48 hrs
Comparison of 0.9% vs 0.45% NS Hydration in Patients Undergoing Coronary Angioplasty
Mueller et al. Arch Int Med, 2002
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Mueller et al. Arch Int Med, 2002
0.7%
2.0 %
0.4%
1.1%
Comparison of 0.9% vs 0.45% NS Hydration in Patients Undergoing Coronary Angioplasty
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Multivariate Analysis for the Development of Contrast Media-Induced Nephropathy
Mueller et al. Arch Int Med, 2002
Risk Factor Odds Ratio P value
Female sex 3.9 0.005
Baseline SCr 6.6* <0.001
NS hydration 0.3 0.037
*increase in SCr of 1 mg/dl
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Sodium Bicarbonate vs Saline in the Prevention of Contrast-Media Induced Nephropathy
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Sodium Bicarbonate vs Saline in the Prevention of Contrast-Media Induced Nephropathy
Merten et al. JAMA, 2004
• Alkalinization of urine inhibits free radical formation
• Reducing free radical formation will decrease CIN
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• SALINE– 0.9% NS
• SODIUM BICARBONATE– 154 mEq/L sodium bicarb
– 3 ml/kg/hr for 1 hr prior– 1 ml/kg/hr for 6 hrs post
Sodium Bicarbonate vs Saline in the Prevention of Contrast-Media Induced Nephropathy
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N Saline Bicarb P value
Total 119 8/59 (13.6%)
1/60 (1.7%) 0.02
Cardiac cath 97 8/48
(16.7%)1/49 (2%) 0.02
Sodium Bicarbonate vs Saline in the Prevention of Contrast-Media Induced Nephropathy
Merten et al. JAMA, 2004
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Saline vs Na-Bicarb in the Prevention of CIN in CKD pts undergoing Angiography: PRCTrials
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Wiedermann & Joannidis. NDT 2010
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Prophylaxis of Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
• Contrast media• Hydration• Pharmacologic agents• Prophylactic dialysis
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• Furosemide and/or mannitol• Calcium channel blockers• Adenosine blockers• Dopaminergic agonists (fenoldopam)• Endothelin receptor antagonists• Atrial natriuretic peptide• N-Acetylcysteine
Pharmacologic Prophylaxis of Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
endothelin release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery
ET receptor antagonists
Diuretics, ANP,CCB
Dopa-1 agonist
Theophylline
N-Acetylcysteine
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Contrast Media
Cellular effects Hemodynamic effects
vacuolization necrosis apoptosis effects mesangial cells inhibits protein reabsorption
Osmolality unrelated
Osmolality related
adenosine release
endothelin release
vasoconstriction
Medullary hypoxia+
Free radicals
Acute Renal FailureIdee et al. Invest Radiol 2004
Osmotic diuresis
Na+ delivery
ET receptor antagonists
Diuretics, ANP,CCB
Dopa-1 agonist
Theophylline
N-Acetylcysteine
XX
XX
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• Stimulates the synthesis of glutathione– Reduces Oxidative stress
• At high dose promotes vasodilatation
• Decreases medullary vascular resistance
N-Acetylcysteine Prophylaxis for Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
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N-Acetylcysteine Prophylaxis for Contrast Media-Induced Nephropathy
• All patients had stable CRI
• GFR <60 ml/min, SCr 2.4 to 2.8 mg/dl
• NAC dose:
• 400 to 600 mg PO BID
• The day before and the day of the procedure
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Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)
• 2,308 pts having coronary or peripheral angio
• 1 risk factor (>70yo, CKD, DM, CHF, low BP)
• NAC 1200 mg BID Pre & Post vs Placebo
• Hydration: NS- 1 ml/kg/hr 6-12 hr pre/post-study
• End point: >25% increase in SCr at 48-96 hrs13% placebo vs 13% NAC (p =0.97)
•End point: >0.5 mg/dl increase in SCr at 48-96 hrs4% placebo vs 4% NAC (p =0.85)
ACT Investigators. Circulation 2011
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Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)
ACT Investigators. Circulation 2011
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Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT)
ACT Investigators. Circulation 2011
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Li et al. PLoS ONE 2012; 7:e34450
Efficacy of Short-Term High Dose Statin in Preventing CIN
• Statins:↑ nitric oxide, ↓ endothelin-1, anti-inflammatory, and anti-oxidative
• Meta-analysis of 7 PRCT comparing high-dose statin (40-80 mg) v. low-dose or no statin
• Short-term statin use lead to a 49% RR of CIN• But statin use was not protective in studies of patients
with ↓ GFR or those receiving NAC
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Prophylaxis of Contrast Media-Induced Nephropathy
Idee et al. Invest Radiol 2004
• Contrast media• Hydration• Pharmacologic agents• Prophylactic dialysis
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Consensus Statements of the CIN Consesus Working Panel and KDIGO AKI Work Group
Statement 10:Prophylactic hemodialysis or hemofiltration hasnot been proven to be efficacious in reducing the risk of AKI after exposure to iodinated contrast.
CIN Consensus Working Panel, Am J Cardiology, 2006
Statement 4.5:We suggest NOT USING prophylactic HD or hemofiltration for contrast-media removal in patients at increased risk for CI-AKI.
KDIGO AKI Work Group, Kidney Int, 2012
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Approach to Patients Receiving IV Contrast
Low risk
Oral Hydration
High risk
Avoid contrast
-DC NSAIDs/Metformin 24-48 hrs prior- Check SCr pre-prophylaxis-Intravenous saline/bicarb hydration-Low dose, non-ionic, low osmolar contrast-Check SCr 24-48 hrs post-procedure
Consensus Panel for CIN, KI 2007/2012
1 ml/kg/h (0.5 ml/kg/hr in CHF pts) for 6-12 hrs pre- and post-procedure
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Consensus Statements of the CIN Consesus Working Panel
Statement 4:
In the setting of emergency procedures, where the benefit of very early imaging outweighs the risk of waiting, the procedure can be performed without knowledge of serum creatinine or eGFR.
CIN Consensus Working Panel, Am J Cardiology, 2006