CONTRAST INDUCED NEPHROPATHY(CI-AKI)

CIN in PCI and

Management

Dr. Nagula PraveenPG I yr (DM)

CONTRAST INDUCED

NEPHROPATHY *

(* CI-AKI)

Introduction Epidemiology Criteria/Definition Patho physiology Risk markers Risk score Contrast agents Clinical features

Management Future... Consensus statements Conclusions Take home message.

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.

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 ?

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).

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.

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

Comparison of RIFLE criteria and CIN criteria

Diagnostic criteria for CIN

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;

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.

Is relative increase in serum creatinine more important than absolute increase in serum creatinine,does it matter much?????

certainly…..

Kidney international;2006:69:S46-50.

Relation of serum creatinine and GFR

Finn et al ;Nephrol Dial Transplant (2006)21;i2-i10

Mc Cullough et al ;AmJ Cardiol 2006;98:5K-13K

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

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.

..\JC\Urine Formation _detailed video_.mp4

Tubuloglomerular feedback:

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

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

“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.

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.

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

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.

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.

Unselective endothelin receptor

blocker

ETB

VASODILATION

Attenuation of

ENDOTHELIN Release

Increased

ENDOTHELIN Release

ETA

VASOCONSTRICTON

Selective ETA antagonism is beneficial

“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

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.

Is there any risk score for CIN ?

Yes

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,anemia,volume of contrast) were assigned a weight integer.

The sum of the integeres was a total risk score for each patient.

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.

Effect of contrast volume on CIN

A patient with CIN requiring dialysis is at high risk of mortalityMc Collough et al.

CIN has impact of poor prognosis in patients with MI

CONTRAST MEDIA

Important considerations in choosing a contrast agent

SOLUBILITY OSMOLALITY VISCOSITY

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.

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.

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.

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}

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)

advantages

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

ISO OSMOLAR CONTRAST AGENTS

Nonionic IODIXANOL (Visipaque) only IOCM used in the cardiac

catherization laboratory.

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..

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.

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.

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.

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.

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.

“..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.

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

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

NON RENAL COMPLICATIONS OF CONTRAST AGENTS

PREVENTIVE MEASURES

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)

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.

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.

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.

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.

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

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.

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;62:2202-2207Goldberg et al – EHJ 2004

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.

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)

Does NAC have deleterious effects on its use??

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.

Recommendations for NAC

Why there are conflicting results ??

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.

ASCORBIC ACID

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

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.

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.

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.

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.

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.

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

CONSENSUS STATEMENTS IN CIN

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.

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.

Is your patient being posted for Angiography /PCI????

Have a check in prescription of these drugs……

They need to be stopped ….

DOSES

RECENT TRENDS IN CI-AKI

STATINS…does they have any role???

Comparison of NAC,Ascorbic acid, Statins

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

Role of heme oxygenase

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.

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

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.

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.

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.

KNOW PREVENTION , NO CIN

NO PREVENTION, KNOW CIN

Finally…. A small quote

THANK YOUThe perfect balance