1. Contrast induced acute kidney injury (CI-AKI) is a common cause of hospital-acquired acute kidney injury that can increase both short and long term morbidity and mortality. 2. Prevention strategies aim to reduce the nephrotoxic effects of iodinated contrast media and are important since treatment options for CI-AKI are limited to supportive measures. 3. While hydration with intravenous fluids is the standard prevention method, evidence for the benefits of specific fluids or adjunctive therapies like N-acetylcysteine is unclear from randomized controlled trials. Larger and higher quality studies are still needed to determine the most effective prevention strategies.

1. Contrast Induced Acute Kidney Injury
Surendra Babu M
2nd year resident
Dept of Nephrology,

2. INTRODUCTION
 CIN (CI -AKI ) third leading cause of acute kidney
injury in hospitalized patients.
 Most frequent renal complication of endovascular
interventional procedures.
 Unrecognized as it is asymptomatic..
 Increases short and long term morbidity and
mortality.
 Treatment is limited to supportive measures while
awaiting the resolution of renal impairement.
 Prevention is the one to be emphasised in case of CI
–AKI.

3. History
 In 1906,Von Lichtenberg and Voelcker used 2% colloidal silver solution,for
retrograde pyelography olleagues,10%studies.(toxic to kidneys,death). In
1920, Osborne and c “NaI” for Rx of syphilis, fortuiously found it to be
radiopaque ,excreted by kidneys.--first pyelogram.
 Selectan - Moses Swick
 Uroselectan ,1927 – increased solubility and less toxicity.
 In 1993, Hippuran was introduced.
 Binz and Rath – Neo ipax(Iodoxyl) and diodrast (Diodone)
 1927 – Werner Frossmann – self catheterization,using urinary catheter(
antecubital vein),(NaI)
 1923,Berbrich and hirsch –femoral angiogram
 1924,Brooks – first angiogram (under GA).

4. The serum creatinine usually
increases within 24 -48hrs after
contrast administration, peaks
at 3 to 5 days,and returns to
baseline in 1 -3 weeks.

5. Is relative increase in serum creatinine
more important than absolute increase in
serum creatinine,
does it matter much?????
certainly…..
Kidney international;2006:69:S46

6. Uniqueness of Contrast
induced AKI
 Universally iatrogenic
 Risk factors well characterised
 Time of insult largely predictable
 Make it amenable to prevention

7. Epidemiology
 Incidence in General population <2%.*
 Overall incidence is 14.5% (epidemiological study)^
 Among diabetics, mild –moderate CKD – 9-40%.#
 Severe CKD 50-90%.
 5% of hospital admissions.**
 Cases of CI-AKI leading to dialysis are rare (0.5 to
2.0%).
 When it leads to dialysis in hospital mortality of
35.7%,18.8% - 2 yr survival rate $ .*Berg et al, Nephroptoxicity related to contrast media.Scand J urol Nephrol 2000;34:317-322.
^Lang et al; incidence of contrast medium induced acute tubular necrosis,radiology 1981:138:203-206.
#Manske et al;contrast nephropathy in azotemic diabetic patients undergoing coronary angiography.
Am J Med 1990;89:615-620.
**Hou et al ;hospital acquired renal insufficiency Am J Med 1983;74:243-248.
Mc collough et al,Am J Med 1997.

8. Course and Prognosis
 1% may need dialysis & in those with severe involvement,
30% may have residual renal impairment..
 At 1 year after PCI, the mortality rate in patients
undergoing dialysis had increased to 45.2%, compared
with 35.4% in patients with CIN not requiring dialysis and
Creat rise Creat peak Return to
baseline
Non-oliguric
CIAKI
48hours 3-5 days 10-14days
Oliguric
CIAKI
48 hours 5-10 days 14-21 days
In a study on 200 patients
undergoing PCI for acute MI, patients
who developed CIN had a longer
hospital stay (13 ±7 days as compared
with 8 ±3 days in subjects without CIN;
p<0.001) and a more complicated
clinical course, in addition to a
significantly increased risk of death.
J Am Coll Cardiol 2004;44:1780 –
1785

12. 0
20
40
60
80
100
120
0 1 2 3 4
number of risk factors
Arch Intern Med 1990;150

17. Left ventricular &-----: 30-45 mL
aortic angiography
PCI-----------------------:150-200 mL
CECT scan--------------:uses 100-150 mL
IVU-----------------------:100-mL bolus of a 50%–
60%
FFA uses Na fluorescein and not assoc with
CIN

20. Contrast Induced AKI
Direct
tubular
toxicity
Oxidative
stress

23. Preventive strategies

27. Preventive strategies for
CIN
 CCB
 Loop diuretics*
 Mannitol*
 Dopamine*
 Fenoldopam*
 ANP
 Hemodialysis*
 NAC
 Theophylline
 Aminophylline
 Ascorbic acid
 Statins
 Hemofiltration
• IVF
Ineffective EffectiveUnclear benefit
* Possibly harmful

30. Oral or IV?
Three times more water required compare with
isotonic sodium solutions to produce the same
expansion of the extracellular space.(60% vs
20%)
Increased GFR –increases clearance of CM-
diminish duration of renal tubular cells
exposure to CM.
Oral intake of NaCl or water may be equally
protective as IV fluids for prevention of CIN.

31. When before/during/after
procedure?
 Administration of fluid immediately before or at
the time of CM exposure is less efficacious for
prevention of CIN.
 Sufficient time to increase urine output,decrease
vasconstrictive forces,replete extracellular volume
are required for optimal protection.
 6 hrs -12 hrs before procedure,12 hrs -24 hrs after
procedure.

32. Rate of CIN: 11% 28% 40%
Solomon R, Werner C, Mann D, D’Elia J, Silva P. N Engl J Med. 1994;331:1416-1420.

34. Isotonic v. hypotonic saline
Mueller C, et al. Arch Int Med. 2002; 162:329-336
P=0.04
P=0.35
P=0.93

35. Saline vs. Bicarbonate IV fluid
13.6%
1.7%
0%
2%
4%
6%
8%
10%
12%
14%
NaCl (n=59) NaHCO3
(n=60)
rate of CIN
(8/59)
(1/60)
Merten et al. JAMA 2004;291:2328-2334
P = 0.02

36. Important limitations of this
study
 Presumed effect size -67%, allowed the study with
small sample size of 260. (33% would have
needed 1300
 Switch of one patient would have resulted in
statistically negative study

39. Clin J Am Soc Nephrol 4: 1584–1592,
Trials those who included patients with CKD2-4 as
well as normal renal function.

40. Power curve: the relationship between trial size and power.
Hiremath S , and Brar S S Nephrol. Dial. Transplant.
2010;ndt.gfq279
© The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights
reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

41. 1. This metanalysis highlights that the perceived
benefit of sodium bicarbonate is largely driven by
small, underpowered RCTs with extreme treatment
effects and wide CIs.
2. Among the large randomized trials there was no
evidence of benefit for hydration with NaHCO3
compared with NaCl for the prevention of CI-AKI.
------CLINICAL EQUIPOISE--------
Clin J Am Soc Nephrol 4: 1584–1592,
Trials those who included patients with CKD2-4 as
well as normal renal function.

42. 1. Although the summary of the published data
favours bicarbonate but this is due the effect of
the smaller, poorer quality trials .

43. NAC for CIAKI (n=83)
0%
5%
10%
15%
20%
25%
Tepel M, et al. N Engl J Med 2000; 343:180-184
%CIN(Scr↑0.5mg/dL@48h)
Control
2%
21%
P=0.01
NAC

46.  Citing these results, 2011 guidelines issued by the
American College of Cardiology/American Heart
Association/Society for Cardiovascular
Angiography and Interventions state that NAC is
not useful for the prevention of CI-AKI and
recommend against its administration

51. poseidon
 Poseidon is one of the
twelve Olympian deities of
the pantheon in Greek
mythology.
 His main domain is
the ocean, and he is called
the "God of the Sea".
 Additionally, he is referred to
as "Earth-Shaker“ due to his
role in causing earthquakes,
and has been called the
"tamer of horses

52. POSEIDON
Aimed to investigative different rates of fluid administration guided by
the left ventricular end-diastolic pressure

54. outcomes
Primary outcome
 Primary endpoint was
increase in the serum
creatinine of greater
than 25% or 0.5 mg/dL
from baseline
Secondary endpoints
 components of the
primary endpoint
 occurrence of major
adverse events at 30
days and 6 months :-
 composite of all-cause
mortality
 myocardial infarction
 or renal replacement
therapy

55. Results
total mean (SD) volume of NS administered was 1727 ml
in LVEDP group vs 812 ml in control group

56. results
 Overall incidence of CI AKI was 11.4% - it was 6.7 % in LVEDP
group vs 16.3% in control group (p = 0.005)
Relative risk was 0.41 (95% CI 0.22–0.79)
NNT 11

61. Serum creatinine concentration at baseline and 24 and 48 hours after contrast media
administration in the control (continuous line) and RenalGuard (dashed line) groups.
Carlo Briguori et al. Circulation. 2011;124:1260-1269
Copyright © American Heart Association, Inc. All rights reserved.

62.  Dual contrast detection/aspiration system (Catharos Medical Systems,Los
Gatos,USA).
 CINCOR removal system (Osprey Medical,USA)
 Automated balance hydration (Renal Guard system).
 REMEDIAL trial – 11.05 % vs 20.5% ,p=0.025,score >11
 MYTHOS trial - 4.6%vs 18.0% (p=0.05),CKD 3 or more
 CIN-RG trial – underway.
 Renal cooling- COOL RCN trial -effect of systemic hypothermia in
prevention of CIN-no benefit. AJC 2011.
 Intra renal drug infusion –Fenoldopam – no benefit in CIN.
 REMOTE ISCHEMIC CONDITIONING –beneficial . Circ 2012

65. KEY POINTS
 The risk of contrast induced nephropathy is directly proportional to the
severity of pre existing renal insufficiency.
 Hydration with NS is the most widely accepted preventive intervention.
 N-acetylcysteine may be effective,but studies have given conflicting results.
 Sodium bicarbonate may be of value,but larger multicenter studies are
needed to determine its true effectiveness.
 Better markers for CIN are needed in near future,taken the disadvatanges of
serum creatinine.(cystatin C,NGAL,KIM,IL-18)
 Contrast volume to be confined to less than half of the GFR of patient.

69. KNOW PREVENTION , NO
CIN
NO PREVENTION, KNOW
CIN

70. Thank you