CIN ,third most common cause of AKI. asymptomatic. prevention is the one to be emphasised in case of CI-AKI.

1. CIN in PCI
and
Management
Dr. Nagula Praveen
PG I yr (DM)

2. CONTRAST
INDUCED
NEPHROPATHY *
(* CI-AKI)

3.  Introduction
 Epidemiology
 Criteria/Definition
 Patho physiology
 Risk markers
 Risk score
 Contrast agents
 Clinical features
 Management
 Future...
 Consensus statements
 Conclusions
 Take home message.

4. 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.

5. QUESTIONS IN MIND
 How CIN occurs ?
 What is the definition of CIN, why change in creatinine only?
 Are contrast agents directly nephrotoxic ?
 How can it be prevented ?
 What is the best prescription for hydration ? IV/oral
 Is sodium bicarbonate better than sodium chloride as an
intravenous hydration solution?
 Is the latest iso-osmolar agent better than the low osmolar agents
currently in use ?
 Why pathophysiology could not be put into practice of
management ?
 Why there are conflicting results?
 Will CIN be never having an effective treatment ?

6. History
 In 1906,Von Lichtenberg and Voelcker used 2% colloidal silver
solution,for retrograde pyelography studies.(toxic to kidneys,death).
 In 1920, Osborne and colleagues,10% “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).

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. Criteria
 Pakfetrat et al were the first to investigate risk factors for CIN
on the basis of RIFLE criteria.
 They found it impossible to reach conclusive results in the
injury and failure categories.
Pakfterat el,Risk factors for contrast related acute kidney injury according to RIFLE criteria,
Iran J Kidney Dis ,2010:4(2):116-122

9. Comparison of RIFLE criteria and CIN
criteria

10. Diagnostic criteria for CIN

11. KDIGO Definition
 CI-AKI is defined by the Kidney Disease Global Outcomes
(KDIGO) guidelines as an
“…increase in serum creatinine of 0.3 mg/dL or
greater within 48 hours of contrast use or a 50% or
greater increase from baseline serum creatinine within 7
days”.
From Kidney disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group.
KDIGO CLINICAL PRACTICAL GUIDELINES FOR ACUTE KIDNEY INJURY.
Kidney Int 2012;Suppl 2:1 -138;

12. course
 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.

13. Is relative increase in serum
creatinine more important than
absolute increase in serum
creatinine,
does it matter much?????
certainly…..
Kidney international;2006:69:S4

15. Relation of serum creatinine and GFR
Finn et al ;Nephrol Dial Transplant (2006)21;i2-i10

16. Mc Cullough et al ;AmJ Cardiol 2006;98:5K-1

17. CI –AKI CHOLESTEROL
EMBOLIZATION
INCIDENCE 2% (14.5%) 0.15% (usually underestimated)
At risk CKD,DM2 Abdominal aortic aneurysm,
diffuse atherosclerosis
Prediction Risk score Episodic HTN, eosinophilia
SIGNS Usually asymptomatic Signs of peripheral
embolization (livedo
reticularis,abdominal foot
pain,purple toes
Decreased urine output
course Develops within in 24-48 hrs Develops slowly over weeks to
months.
Returns to baseline in 1-3
weeks
Progress to frank renal failure
(50%)
Renal replacement therapy -
dialysis
Usually not needed (2%) Half of the patient progress to
frank renal failure requiring
dialysis

18. RENAL PHYSIOLOGY
 Each kidney has about 1 million nephrons.
 Renal vascular bed – vasa recta, has a high vascular resistance.
 Afferent and efferent arterioles control blood flow through renal
capillaries.
 Glomerular filtration – balance of three forces.
 Plasma colloid oncotic pressure - 15 mm Hg.
 Bowmann’s hydrostatic pressure – 30 mm Hg
 Glomerular capillary pressure – 55 mm Hg (most dominant force).
 Net filtration pressure = GCP – (PCP + BHP) ; 55 -45 = 10 mmHg;
allows fluid to be forced away from blood through permeable
membrane – glomerular filtration.

20.  ..JCUrine Formation _detailed video_.mp4
 Tubuloglomerular feedback:

22. Pathophysiology
 Combination of toxic and ischemic injury to renal tubular
cells.
 Rheological alterations
 Activation of tubuloglomerular feedback
 Vasoconstriction
 Decreased blood flow
 Regional Hypoxia
 Cytotoxic effect on renal epithelial cells
 Generation of ROS
 Increased adenosine or endothelin production

25.  Vasa recta - same diameter as usual capillaries,increased
vascular resistance (several fold longer ).
 Viscosity of blood flow through vasa recta is maintained very
low.
 Low hematocrit – high flow velocities by erythrocytes.
 Plasma skimming – right angled arteries.
 R =   8  l /  r4

26.  “Osmotic diuresis theory” – hyperosmotic contrast media – diuresis
– TGF – decreased RBF – decreased GFR.
 Osmolality has no effect on tubuloglomerular feedback –
mannitol,frusemide.
 Regional hypoxia – deeper portion of outer medulla –thick ascending
loop of henle – exhibit hypoxic damage -high o2requirement due to
salt absorption. Adding contrast media –aggravates hypoxic injury.
 Isoosmolar agent (IODIXANOL) causes low BP – decreased blood
flow to all regions in kidney .
 Remnant nephron theory – e GFR < 60ml/min/1.73m2 ,remaining
nephrons are vulnerable to hypoxic injury,as they are at increase need
of oxygen.

27. Cytotoxic effects on renal tubular cells
 Hardick et al – effect on apoptosis was not found ,proliferation
impaired. – reduced proliferation will affect renal function with a
delay of hours – clinical course of CIN.
 “Vacuolization” of cells -morphological hallmark, rather than an
indicator of damage.
 Perturbation of mitochondrial enzyme activity – increased adenosine.
 Depends on ionicity,molecular structure.
 Ionic compounds –most profound effect.
 Apoptosis induced in distal tubule – polarity of cells affected,opening
of intercellular junctions.

28. Reactive oxygen species
 O2(- ),OH- more reactive than H2O2.
 “superoxide theory”
 Endothelial dysfunction
 Tonic influence of NO in renal microvasculature is impaired.
 Superoxide rapidly scavanges NO –attenuation of NO activity.
 Increased in diabetic nephropathy.
 ROS – extracellular signalling molecules – mediates AT II,
TXA2,ET1,adenosine,NE.
 Role supported by allopurinol.
 Was the background for positive role of NAC in CIN prevention

29. Adenosine
 Exerts a vasoconstrictor response on afferent arteriole (A1
receptors).
 A1- vasoconstriction, contracts mesangial cells in the
glomerulus.
 Osswald – “adenosine is mediator of TGF”.
 Higher sensitivity of renal vasculature to adenosine is found in
Diabetes Mellitus.
 Blocking A1 receptors failed to alleviate medullary
hypoperfusion and hypoxia in repsonse to contrast media.
 A2A receptors increases medullary flow.

30. Endothelin
 Effects of endothelin dependent on the receptor subtype
activation.
 ETA- vasoconstriction.
 ETB – endothelin dependent NO release.
 Increased endothelin concentration in plasma and urine.
 Exaggerated in pts with renal insufficiency.
 Unselective receptor blocker – more vasoconstriction.

31. Unselective
endothelin
receptor blocker
ETB
VASODILATION
Attenuation of
ENDOTHELIN Release
Increased
ENDOTHELIN
Release
ETA
VASOCONSTRICTON
Selective ETA antagonism is beneficial

32.  “The most accepted explanation is that contrast media causes
vasoconstriction via release of vasoconstrictors, such as
endothelin and adenosine, which in the presence of already
compromised renal hemodynamics cause medullary ischemia.
injury to tubular epithelium seems to be mediated by reactive
oxygen species.”
Aqeel et al ,nephrotoxicity of different contrast media,Interven Cardio clinics(3) 2014

33. Why CIN does not occur in all ?
 With normal systemic and renal circulation,radiographic
contrast agents does not cause renal failure,the compensatory
mechanism are intact.
 Renal medulla is highly vulnerable to hypoxia.
 When there is a disruption of the balance between the
VASODILATORS(beneficial) and VASOCONSTRICTORS
(harmful),the latter predominating- renal failure occurs
secondary to increased renal hypoxia.
Brezis and Rosen et al,Hypoxia of the renal medulla;its implications for disease.NEJM;1995;332:647-655.

35. Is there any risk score for CIN ?
Yes

37.  8,357 pts –randomly assigned to development and a validation
dataset.
 Baseline and procedural characteristics of the 5,571 pts in the
development dataset were considered as univariate predictors of
CIN (increase >25% and or >0.5mg/dl in S.Cr at 48 hrs after PCI
vs baseline).
 Multivariate regression analysis for idenfying independent
predictors of CIN with a p value <0.0001.
 Based on the odds ratio,eight identified
variables(hypotension,IABP,CCF,CKD,Diabetes,Age>75yrs,anemi
a,volume of contrast) were assigned a weight integer.
 The sum of the integeres was a total risk score for each patient.

38. Integer – whole number ,2 for 0.5 value of OR.
 The overall occurrence of CIN in the development set was 13.1 %
(range 7.5% vs57.3% for a low 5 and a high ≥ 16 score,
respectively).
 Rate of CIN raised exponentially with increased risk score.
 Good discrimative power in the validation dataset.(c statistic -
0.67).
 Exclusions : Pts with pre-existing ESRD requiring dialysis and
other contrast exposure within one week or less from index
procedure,pts with PCI treated for Acute MI,patients in shock
were excluded from analysis.
 Hydration : 1 ml/kg/h of 0.45%NS for 4-12 hrs before PCI,18-24
hrs after PCI.

44. Effect of contrast volume on CIN

45. A patient with CIN requiring dialysis is at high
risk of mortality
Mc Collough et al.

46. CIN has impact of poor prognosis in
patients with MI

48. CONTRAST MEDIA

49. Important considerations in choosing a
contrast agent
 SOLUBILITY
 OSMOLALITY
 VISCOSITY

50.  Classified into ionic and nonionic groups based on water
solubility.
 Ionic agents, water soluble, dissosciate into negative and
positive ions, bind with negative and positive poles of water
molecules.
 Nonionic agents donot dissosciate,but are water soluble,polar
OH groups.

51. TYPES OF CONTRAST MEDIA
 Based on osmolality relative to plasma
 HIGH OSMOLAR CONTRAST AGENTS (HOCM)
 LOW OSMOLAR CONTRAST AGENTS (LOCM)
 ISOOSMOLAR CONTRAST AGENTS (IOCM)
Further classification is by contrast agent ratio
No. of iodine atoms/No. of particles in solution.
Most imp. factor impacting attenuation.

52.  Basic structure of a benzene ring.
 Triiodinated benzene rings(2,4,6).
 Iodine augments attenuation, increases the linear coefficient of
radiation.
 Monomers (one triiodinated ring),dimers (two).
 Attachment at the first carbon atom differentiates ionic from
non ionic contrast agents.
 Sodium/Meglumine – ionic
 Amide group – nonionic
 OH groups 1,3,5 – solubility,decrease protein binding.

57. HIGH OSMOLAR CONTRAST AGENTS
 Single, negatively charged triiodinated benzene ring attached to
sodium or another cation, such as meglumine.
 Negatively charged anion is Radiopaque.
 Sodium content of the agents is equivalent to that of blood.
 Inexpensive.
 SODIUM ACETRIZOATE (UROKON) 1951
 SODIUM DIATRIZOATE (HYPAQUE) 1956
 ISOPAQUE
 Side effects because of osmolality (5-8 times physiologic ) {PAIN}

58. LOW OSMOLAR CONTRAST AGENTS
 Metrizamide (metrizoic acid and glucosamine, water soluble with low
osmolality).
 Osmolality 485 mOsm
 It ppts with high temperature (sterilization)
 Minimize effects related to hypertonicity.
 IOPAMIDOL (Iopamiro)
 IOHEXOL (Omnipaque)
 IOPROMIDE (Ultravist)
 IOVERSOL (Optiray)
 IOBITRIDOL (Xenetix)
 IOXAGLATE (Hexabrix) (6 :2) (Nausea,Vomiting)

59. advantages
 Intravascular agents of choice today.
 Lack of a glucose radical.
 Ability to be autoclaved
 Easier synthesis
 Less expensive to produce

60. ISO OSMOLAR CONTRAST AGENTS
 Nonionic
 IODIXANOL (Visipaque) only IOCM used in the cardiac
catherization laboratory.

61. ROLE OF OSMOLALITY
 Effect of the osmolality on degree of apoptosis in a renal
epithelial cell line using DNA fragmentation as a marker.in
these experiments salt and mannitol solutions with osmolality
comparable to that of HOCM did not cause much
fragmentation as HOCM,suggesting a direct toxic effect on the
renal epithelial cells that is unique to contrast media.
 Mitochondrial dysfunction.
 IOCM more nephrotoxic than HOCM,LOCM – increased
viscosity and tubular hydrostatic pressures.
 Greater reduction in medullary blood flow with IOCM.
 Osmotic nephrosis i.e swelling and vacuolization of proximal
Renal tubular cells. – Dickenmann et al..

62. Viscosity
 Should have lowest attainable viscosity.
 Contrast media may induce high viscosity in the renal
tubules,affecting renal function (not confirmed in humans)
 Lowest viscosity (High osmolar contrast agents) much more
nephrotoxic .
 Is of minor importance.
 Dimers have higher viscosity than monomers
 Ionic contrast media lower than nonionic.

64. Comparison of different osmolar
agents..which is beneficial ??
 Iohexol cooperative study;Rudnick et al – IOHEXOL vs
DIATRIZOATE,iohexol was less nephrotoxic in patients with CKD 
Diabetes.(7% vs 4% ,27% vs 12%)
Kidney Intern 1995;47(1):254-61
 No difference in nephrotoxicity in patients with normal kidney
function,with or without diabetes.

65. IODIXANOL vs LOCM
 NEPHRIC trial – diabetics,serum cr -1.5 -3.5 mg/dl (3% vs 26%)
(p=0.02) iodixanol vs iohexol .
NEJM 2003;348(6):491-9.
 RECOVER trial – iodixanol vs ioxaglate (7.9% vs 17%,p=0.021), in
pts with severe CKD (12.5% vs 53.3%),diabetics (10.4% vs 26.5%)..
JACC 2006;48(5):924-30.
 CARE trial – contrary findings – moderate to severe CKD pts,no difference in
CIN.(6.7% vs 4.4% p=0.39) iopamidol Circulation 2007;115(25);3189-96.
 VALOR trial –ioversol – (21.8% vs 23.8%). Am H J 2008;156(4);776-82.
 IMAPCT trial ,PREDICT trial ,ACTIVE trial - IV studies. - no difference in
nephrotoxicity.

66.  When all studies pooled together ,no difference in the risk of
CIN was seen between iodixanol and other LOCM( relative
risk ,0.80.P=0.1).
 Better when compared with iohexol (p=0.01)
 In the intravenous group,reduction in CIN risk was not found
with iodixanol compared with other LOCM(RR -
1.08,p=0.79),not even in high risk patients with underlying
CKD and diabetes.

67. Why iodixanol was not beneficial in all
patients ??
 Increased viscosity of iodixanol,resulting from its dimeric
composition.
 Increased RBC aggregation – stasis in renal tubules – tubular
ischemia.

68.  “..it is often thought that iso osmolar contrast media are superior to
low osmolar agents,since they would not increase resistance to a
similar extent”---- NOT TRUE - ? OSMOLALITY PLAYS NO ROLE
FOR BLOOD FLOW WHILE VISCOUS PROPERTIES ARE
DECISIVE.
 Q =  P    r4 /  8  l
 Monomeric contrast media - higher viscosity – decreases medullary
blood flow – decreased p02 levels.
 …..not only the intrinsic viscosity of fluid is important but also their
interaction with blood constituents.
High osmolar agents – diminish erythrocyte deformability – increases stiffness
– difficulty to pass through capillaries – trapping in vasa recta.

69.  Adverse effects if augmented fluid viscosity by the use of dimeric
contrast media may be more pronounced in renal tubules than in
capillaries.
 Dimeric contrast media -  viscosity -  flow -  resistance
 40 mm Hg
 markedly towards the distal section of kidney due to
fluid reabsorption

Urine becomes concentrated
Tubular fluid viscosity increases
Tubular plugging
Hydration attenuates fluid reabsorption

70.  Dimeric contrast media should be prewarmed before
infusion;since they markedly reduces viscosity.

71. NON RENAL COMPLICATIONS OF
CONTRAST AGENTS

76. PREVENTIVE MEASURES

77. Four basic concepts
 1.hydration and volume expansion
 2.choice and quantity of contrast material (IOCM or LOCM)
 3.pre,intra,post procedural end organ protection with
pharmacotherapy.
 4.Post procedural monitoring and expectant care. (24-48 hrs
post procedure s.creatinine),(dialysis need in patients with
eGFR<30ml/min/1.73m2)

79. HYDRATION
 Simplest and most effective way of protecting renal
function.(decreases by 50% chance of CI-AKI)
 Effect of contrast agents on kidney is prolonged in
dehydration.(RBF,GFR).
 0.9% NS by IV infusion at a rate of approx.
 1-1.5ml/kg/hr.(adjust accordingly).
 Atleast 300-500ml of IV hydration before administration of contrast
material.
 6-12 hr before the procedure and continued for upto 12-24 hr after the
radiographic examination,if diuresis is appropriate.
 Urine output 150ml/hr.(if more – replace the lost fluids)
 Eisenberg et al .
 Solomon et al (CKD pts -0.45% NS).
*AJR 1981;136:859-861.
^NEJM 1994;331:1416-1420.

80. Oral or IV?
 Only about 2/3 pts receive hydration as per the guidelines.
 Three times more water required compare with isotonic sodium
solutions to produce the same expansion of the extracellular
space.(60% vs 20%)
 Even in the euvolemic state,administration of a sodium load
decreases sodium reabsorption in the proximal tubule and loop of
henle and increases urine volume.
 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.

81. 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.

82. NaHCo3 or NaCl ??
 Merten et al.119 pts
 2 cohorts,IV solution 154 mEq/L(3ml/kg 1 hr before,1.5ml/kg/hr
during,for 4hrs therafter)
 NaHCo3 superior to NaCl
 Rates of CIN (1.7%,n=1 vs 13.6%,n=8)
 Free radical formation (acidic environment) can be inhibited by
increasing the pH of normal extracellular fluid,with use of
bicarbonate.
 NaHCo3 – effective and safe alternative to Normal saline.
 BOSS (Bicarbonate or Saline Study) TCT 2013,no difference in
the incidence of CIN in pts with CKD 3b,4,5 undergoing
CAG,PAG.
 Veterans affairs trial – role of NaHco3 –definitive answer.

83. Imp. note
“Despite the fact that no controlled randomized trial with
sufficient statistical power has been rigoursly performed to prove
the benefit of hydration as scientific fact, it is almost universally
accepted as an appropriate and safe measure to prevent contrast
induced nephropathy…”
Gleeson and Bulugahapitiya et al
AJR2004;183:1673-1689

85. N-Acetyl cysteine
 Reactive oxygen species have a role in renal damage caused by
contrast agents.
 Thiol containing antioxidant.
 Proved beneficial in acetaminophen poisoning.
 Free radical scavanger or a reactive sulfhydryl compound
increasing the reducing capacity of the cell.
 S- nitrosothiol,stable and potent vasodilator.(peroxynitrite
production is limited).
 Improves the expression of NO synthase,improves blood flow.
 blocks expression of VCAM-1,NFKB in glomerular mesangial
cells.

86. Literature on role on NAC in CIN
prevention
 NAC – 1200 mg/day,given orally in divided doses on the day
before and the day of administration of the contrast
agent,beneficial in CKD pts - Tepel et al .*
 APART trial #
 Durham et al – negative results (intra arterial,high dose of
contrast)(1200 mg 1 hr before ,and then 3 hr afterward).²
 Allaqaband et al – (1.6 mg/dl ,Cr Cl <60ml/min).
 Goldenberg et al -600 mg tid,increase in serum creatinine
(10% vs 8%)
 ACT trial-no benefit.
*Prevention of contrast induced reduced renal functions by NAC ,NEJM 2000;343:180-184
#APART trial – Am J Cardiol 2002;89:356-358.
²NAC in CAG ptsKidney International2002;62:2202-2207
Goldberg et al – EHJ 2004

87. Imp note.
 NAC reduces the occurrence of contrast induced nephropathy after
nonionic contrast medium administration by half in high risk
patients.
 Seven trials,805 pts
 NAC +NS reduced the relative risk of CIN by 56%(p=0.02).
 No trial to date has investigated the effect of NAC on hard clinical
end points such as in hospital morbidity rates,mortality rates,or
dialysis dependency.
 Combats cardiovascular disease (40% lower ) Birck et al.
Birck et al ,Lancet 2003;362:598-603

88. An oral dose of 600 mg twice daily the day before and the day of
procedure is the most commonly used regimen.
IV doses of 150mg/kg over half an hour before the procedure or
50mg/kg administered over 4 hrs(critically ill pts)
1200mg >>>> 600 mg +NS
Briguori et al
High dose contrast use group benefited significantly from
preprocedural NAC (18.9 %vs 5.4% ,p=0.04)

89. Does NAC have deleterious effects
on its use??

90.  Results of the ACT study have been considered in most of the
current guidelines,donot support the use of this drug as
preventive measure of CI-AKI.
 Result of the PRESERVE trial are awaited.

92. Recommendations for NAC

93. Why there are conflicting
results ??

94. Ascorbic acid
 Potent water soluble antioxidant
 Scavanges reactive oxygen compounds.
 Increases NO availability,alkalizes the urine.
 Sadat and colleagues et al,meta analysis – ascorbic acid
beneficial in patients at risk of CIN.

95. ASCORBIC ACID

98. Diuretics
 Beneficial in animal studies but not in humans.
 Anto et al – mannitol beneficial 250 ml 20%/hr with hydration
before and after procedure –(22% CIN in Rx group,70% NS
group)
 Solomon et al – exacerbation of CIN on use of furosemide or
mannitol.
 Weinstein et al –worsening of renal function
 Weisberg et al – no protective effect.
1.Arch Internal Medicine,1981;141:1652-1656.
2.NEJM,1994;331:1416-1420
3.Nephron 1992;62:413-415.
4.Kidney Int 1994;45:259-265

99. ANP
 Increases GFR,glomerular hydrostatic pressure by dilating
afferent arterioles and constricting efferent arterioles,while
blocking tubular reabsorption of sodium and disrupting the
tubuloglomerular feedback mechanism.
 The Auriculin Anaritide Acute Renal Failure Study
Group,multicenter,randomized,double blind placebo controlled
trial. – detrimental effect of anaritide in oliguric patients
 Lewis et al –significant drop in BP in anaritide group.
 Kurnik et al – detrimental effect.

100. Calcium channel blockers
 Role of calcium as a mediator in CIN.
 Neumayer et al – Nitrendipine. (Beneficial)
 Solomon et al – no benefit (78 pts).
 Khoury et al – Nifedipine10 mg,administered 1 hr before
imaging made no statistically significant difference in renal
function.
 Larsson et al – no benefit of felodipine in diabetics.
 Failed to gain as a prophylactic tool to date.

101. Adenosine antagonists
 Adenosine, a potent vasoconstictor agent, mediator in TG
feedback.
 Theophylline
 In the wake of a lack of consensus in clinical studies,coupled
with potential side effects of theophylline ( such as a
propensity to cause arrhythmias and convulsions),narrow
therapeutic index,adenosine antagonism cannot yet be
recommended for routine prophylactic use in the current
clinical setting.

102. Dopamine agonists
 Potent vasodilator of the renal arteries.
 Hans et al – dopamine infusion of 2.5ug/kg/min ,during and
after procedure – small improvement in renal function (n=60).
 Recent reports failed to show the benefit of dopamine,instead
it prolonged the duration of CIN.
 Allaqband et al –Fenoldopam(selective dopamine 1 agonist,6
times more potent) – no additional benefit.
 No longer recommended for CIN prophylaxis.

103. Hemodialysis or hemofiltration
 Removal of contrast media by hemodialysis after procedure in
patients with preexisting renal failure,no effect on CIN,and is
unwarranted as a routine procedure.
 Vogt et al –hemodialysis vs IV hydration
 Hemofiltration beneficial than hemodialysis – Marenzi et al –
hemodynamic stability,preserved blood volume,preventing
hypoperfusion.
 Relatively high cost.
Vogt et al,Am J Med 2001:111:692-698.
Marenzi et al ,NEJM 2003;349:1333-1340.

104. TRIALS IN CIN
 APART trial
 REMEDIAL trial
 ISLAND trial
 RECOVER study
 CARE study
 MEENA trial
 P.R.I.N.C.E study
 PREPARED
 MYTHOS
 PROMISS
 ARYMDA CIN
 ACT trial
 PRESERVE trial
 BOSS study

105. CONSENSUS STATEMENTS IN CIN

106. KDIGO guidelines for CIN
 CIN be defined and staged according to the KDIGO recommendation
for the definition of AKI.
 Individuals who develop changes in kidney function after
administration of Intravascular contrast media should be evaluated
for CIN and other possible causes of AKI.
 Risk for CIN,screen for pre existing CKD.
 Alternative imaging methods should be considered at increased risk of
CIN.
 Lowest possbile dose of contrast medium to be used.
 IOCM or LOCM to be used.
 Doesnot specifically comment on preferential aviodance of iohexol in
patients at high risk of CIN.
 IV volume expansion with NS or NaHCO3 solutions,use of oral NAC
in patients at risk of CIN.

107. ACCF/AHA 2012 updated guidelines for
UA/NSTEMI
 Donot recommend the use or avoidance of any particular IOCM or
LOCM in view of the inconsistent relationships between the
various contrast agents and CIN.
 Recommend adequate hydration before angiography,choice of
fluid no preference.
 Benefit of NAC as an adjunct to hydration ,no recommendation on
the use of NAC.
 Contrast media to be less than 30 ml for a diagnostic and less than
100 ml for an interventional procedure.
 Advantageous of >10 days between the first and second contrast
contact if CIAKI has occurred with first procedure.

108. Is your patient being posted for
Angiography /PCI????
Have a check in prescription of these drugs……
They need to be stopped ….

110. DOSES

112. RECENT TRENDS IN CI-AKI

113. STATINS…does they have any role???

114. Comparison of NAC,Ascorbic
acid, Statins

116. PRACTO ACS
 Consecutive statin naïve NSTEACS pts scheduled to undergo
CAG
 Randomly assigned 40 mg rosuvastatin on
admission,20mg/day(n=252) or no statin treatment (n =252).
 The incidence of CI-AKI was significantly lower in the statin
group than in controls (6.7% vs 15.1%,p=0.003).
JACC,63;1.2014:71-9

117. Role of heme oxygenase

118. Future
 The risk of CIN may increase upto 40%,in high risk pts with
every additional 5 ml of contrast media used. AJM 1990.
 One source for mitigation of largely wasted contrast volume
is attributable to excess coronary ostial reflux.(60% contrast
injections).
 A device designed to attenuate the loss of contrast caused by
reflux by altering the contrast injection pressure profile
 AVERT clinical trial (NCT 01976299).
 Automated injection systems beneficial ?? - <3% reduction in
contrast volume – GURM et al. JACC 2013.

121.  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

122. 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.
 Statins use,lower incidence of CIN (best pharmacological strategy for
prevention).
 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.

123.  Newer contrast agents that are nonionic and of lower osmolality than
older agents are less nephrotoxic, but still can cause nephropathy.
 Hemofiltration – large RCTs should be performed before
recommended as standard prophylaxis against CIN in high risk
patients.
 Theophylline cannot be recommended as standard prophylaxis
against CIN.

124. TAKE HOME MESSAGE
 Better markers for CIN are needed in near future,taken the
disadvatanges of serum creatinine.(cystatin C,NGAL,KIM,IL-18)
 Adequate hydration is important in a patient being posted for
CAG,PCI, especially those with risk factors.
 IOCM or LOCM to be used in patients at high risk of CIN, but not to
use iohexol or ioxaglate if LOCM were to be used.
 Contrast volume to be confined to less than half of the GFR of
patient.
 CIN occurrence assosciated with increased morbidity and mortality.
 Role of pharamocological agents need further studies.

125. KNOW PREVENTION , NO CIN
NO PREVENTION, KNOW CIN
Finally…. A small quote

126. The perfect balance