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Contrast induced Nephropathy

Definition
An increase in serum creatinine
0.5 mg/dl (44 mol/L)
25% above baseline

An increase in serum creatinine within


3 days of contrast administration
There is no alternative pathology
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Clinical features
Begins immediately after the contrast
study
Recovery of renal function typically begins
within 3-5 days
Non oliguric for the vast majority of
patients
No medical treatment for established CIN,
so approaches to renal protection and
prophylaxis is important
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Epidemiology
In patients with normal renal functioneven in the presence of diabetes- the risk
is low (1-2%)
In patients with pre-existing renal
impairment or in the presence of certain
risk factors, such as the combination of
CKD, and diabetes, CHF, advanced and
concurrent nephrotoxic drugs- incidence
as high as 25% .

Implications of CIN
CIN may result in any or all of the following
Delay in discharge of patient
Permanent kidney damage
Dialysis
1% CIN patients go on to require dialysis, higher (3.1%) in
patients with underlying renal impairment
DM+ severe renal failure: rate of dialysis may be up to 12%

Increased patient mortality


those who need dialydid do consideraly worse, with in hospital
mortality rates of 35.7% vs 7.1% in nondialysis group and 2 year
survical rate of 19%

Pathophysiology of CIN
Renal vasoconstriction
High osmolar contrast agent Release of endothelin
and adenosine (from endothelial cells) + stimulation of
juxtaglomerullar apparatus Renal vasoconstriction
DM & heart failure increase the risk of contrast-induced
renal failure possibly due to impaired nitric oxide
generation reduce vasodilatation

Direct Tubular Toxicity


A. Epithelial Cell Integrity
B. Oxidative radicals
C. Apoptosis

Direct Tubular Toxicity


A. Epithelial Cell Integrity: High osmolar contrast
media caused detachment in cultured cells. Studies
found that proximal tubular isolates had reduced
ATP and increased intracellular calcium content (a
marker of injury) after radiocontrast exposure
B. Oxidative radicals: Osmotic stress can initiate
the production of reactive oxygen species (ROS)
and radiocontrast has similarly been shown to cause
their generation presumably through osmotic affects
C. Apoptosis: Radiocontrast results in apoptosis of
tubular epithelial cells in vivo and in cultured cells

Risk factors
Pre-existing renal impairment is the most
important risk factor above all other risk factors
for developing CI-AKI.
Risk becomes clinically important when
baseline SCr 115mol/L in men or 88.4mol/L in women
(eGFR<60ml/min/1.7 ) [CI-AKI Concensus Working Panel]
baseline SCr 115mol/L [Bruce et al]

Recommendations:
screen for acute and chronic kidney disease (Serum
creatinine)
precautions to reduce risk implemented when
baseline eGFR <60ml/min/1.7

Patient- related risk factors

Recommendations:
Renal insufficiency
Delay whenever possible contrast
DM with renal insufficiency
media in circulatory collapse/ CHF
Advanced age
until hemodynamic status restored
Volume depletion
Repeated exposure delayed for
Hypotension
48H in patients without risk factors
Low cardiac output
72H in DM/ pre-existing chronic
Metabolic syndrome
renal dysfunction
Hyperuricemia
If AKI after contrast media,
Hypoalbuminemia <35g/L
repeated exposure delayed until
Renal transplant
SCr has returned to baseline
Multiple myeloma
Stop concurrent nephrotoxins
Nephrotoxins- NSAIDs,
aminoglycosides, amphotericin Insufficient evidence to discontinue
B, high doses loop diuretics,
ACE-I/ ARB
acyclovir/ foscarnet
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Procedure related risk factors


Large volume of
contrast
Multiple procedures
within 72 hours
Intra-arterial
administration
Radiocontrast types
Ionic> nonionic
high osm> low osm>
iso-osmolar

Use the lowest possible


dose
Use iso-osmolar/ low
osmolar iodinated
contrast media

Management
No effective treatment for
radiocontrast-induced nephropathy
Key point - PREVENTION

15

Hydration
The cornerstone of CIN prevention
IV volume expansion with either isotonic NaCl or Na
bicarbonate solutions recommended in patients at
increased risk
No clear evidence to guide optimal rate and duration
A good urine output >150ml/H in the 6H post procedure is
associated with reduced AKI rates can be achieved by
1.0ml/kg/H of IVD 3-12H prior and 6-12H after exposure [CIN
Concensus Working Panel]

Isotonic saline superior to one-half normal saline

[Mueller et al]

Oral fluids, while beneficial, is not as effective as IV


volume expansion
16

Na bicarbonate?
Possible but inconsistent benefits
decrease generation of free radicals mediated by Haber- Weiss
reaction (hydrogen peroxide and an oxygen ion from superoxide
form a hydroxide ion) by increasing tubular pH (most active at lower
pH levels)
scavenge potent oxidant peoxynitrate through nitric oxide-mediated
pathyway

Found by some researchers to be more protective than NS


alone
Disadvantages
Isotonic bicarbonate composed by adding 154ml 8.4% Na
bicarbonate to 846ml 5% glucose solution 3ml/kg/H for 1H prior +
1ml/kg/H for 4-6H after
Possible errors during mixing leading to infusion of hypertonic
solution
Burden for preparation
17

N-acetylcysteine (NAC)
Protective effect in many but not all studies, routinely used as:
low cost
lack of adverse effects
potential beneficial effects: relative risk reduction 0.37- 0.73

Scavenger of reactive oxygen species


A thiol-containing antioxidant
Indirect antioxidant effect by facilitating glutathione biosynthesis
(an antioxidant).
A potent vasodilator, increase the expression of nitric oxide
synthase and the biological effects of nitric oxide.
Tab NAC 600 mg bd for 2 days, started 1 day before and
continued on day of procedure
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What if needed to be given as emergency ?


iv NAC at 150 mg/kg in 500mL NS
administered intravenously over 30
minutes immediately before contrast
exposure
Followed by iv NAC 50 mg/kg in 500mL
NS given intravenously over 4 hours
*Provided no contraindications to volume expansion

19

Prophylatic HD
Another proposed method of protection in
high-risk patients is prophylactic
hemodialysis after the contrast study to
remove the contrast agent from the
circulation
Two randomized trials have found no
benefit with this strategy
Do not recommend prophylactic
hemodialysis in high-risk patients.
Vogt, B, Ferrari, P, Schonholzer, C, et al. Prophylactic hemodialysis after
radiocontrast media in patients with renal insufficiency is potentially
harmful. Am J Med 2001; 111:692.
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Other agents
Fenoldopam: not
recommended

Specific dopamine A1 receptor


agonist- might thereotically
increase blood flow to the renal
medulla
No significant benefit proven in
two large scale randomized trials

Theophylline: not
recommended

adenosine antagonists
narrow therapeutic index with
inconsistent results

21

22

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Management
Decline in renal function
The most common manifestation of CIN is asymptomatic
transient decline in renal function, which usually normalizes
within 10-14 days

Serial creatinine
patient at high risk should be followed up with serial creatinine
measurements daily for 5 days

Electrolyte and fluid balance


if oliguric renal failure occurs, manage as per acute renal
failure due to other causes, including judicious acid base,
electrolyte, and fluid balance

Dialysis
temporary dialysis may be required in severe cases, with a
minority of patients requiring permanent dialysis
24

Reference
KDIGO Clinical Practice Guideline for
Acute Kidney Injury 2012
http://emedicine.medscape.com/article/24
6751-overview
Update on contrast induced nephropathy
An article from the e-journal of the ESC
Council for Cardiology Practice Vol. 13, N
4 - 04 Nov 2014

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