Ci aki for nst 2015

CONTRAST INDUCED ACUTE KIDNEY INJURY

ARKOM NONGNUCH, MD. RENAL UNIT, DEPARTMENT OF MEDICINE, FACULTY OF MEDICINE, RAMATHIBODI HOSPITAL, MAHIDOL UNIVERSITY

OUTLINE

• Definition and epidemiology of CI-AKI

• Pathophysiology, natural history, and differential diagnosis of CI-AKI

• Population at risk for CI-AKI

• Prevention strategies of CI-AKI

• Future direction for prevention of CI-AKI

RIFLE VS AKIN

Critical Care 2007, 11:R31 Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Definition of CI-AKI

Parameters Prior 2007 After 2007*

↑SCr 0.5 0.3 or 1.5 time

↓eGFR 25% 25%

Timing within 48 hrs within 48 hrs

Urine volume not stated<0.5 ml/kg/hour for 6

hours

Critical Care 2013, 17:204

*Staged for severity according to the AKIN criteria

#The cause of AKI should be determined whenever possible

Epidemiology of CI-AKI (In-Hospital)

American Journal of Kidney Diseases, Vol 39, No 5 (May), 2002: pp 930-936

Cause Episodes Mortality (%)

↓Renal perfusion 147 13.6

Medications 61 15

Contrast media 43 14

Postoperative 35 2.8

Sepsis 25 76

Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

CI-AKI as a risk of deathIn

-Hos

pita

l M

orta

lity

(%)

0

10

20

30

40

No AKI AKI Dialysis

35.7

7.11.1

Am J Med 1997; 103: 368-375.

P<0.0000001


Reduce nephron mass vulnerable to injury (CKD) DM, poor renal perfusion, nephrotoxic drugs

Contrast enters renal vasculature

Adenosine release from macula dense

Endothelin releaseProstaglandin dysregulation

Sustain intrarenal vasoconstriction (hours/days)

Prolonged contrast transit time in kidney Medullary hypoxia

Osmotic injury and ATN Ischemic injury and ATN

AKI

Pathophysiology of CI-AKI


CI-AKI VS Cholesterol emboli

Parameters CI-AKI Cholesterol emboli

Risk Hypotension, CHF, CKD CVD risks

Route Intra-arterial or venous Intra-arterial

Exposure High volume of radio contrast Thrombolytic or anticoagulant

Onset of AKI 24 hr Week

Reversible Mostly within 1-2 week Rarely

Others signs None signs of embolic and vasculitis

complement level

normal low C3 and/or C4

UA Bland Bland/proteinuria/microscopic hematuriaPrevention Yes No

Prognosis Good Poor

“Risk comes from not knowing what you're doing.” ―Warren Buffett

Clin Exp Nephrol. 2013 Aug;17(4):441-79

DM and CKD considered high risk for CI-AKI


Risk factors of CI-AKI

Eur Radiol (2011) 21:2527-2541Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

CI-AKI risk scoring system

JACC Vol. 44, No. 7, 2004*Formula for eGFR: 186 × (serum creatinine [mg/dL])−1.154× (age)−0.203× (0.742 [for women]) × (1.21 [for African Americans]).

Risk factor Score

SBP<80 mmHg for >1 h and requiring inotropic of IABP support within 24 h of procedure 5

Use of IABP 5

Heart failure, NYHA class III/IV and/or history of pulmonary edema 5

Age >75 years 4

Hct <39 % for men, <36 % for women 3

Diabetes 3

Contrast media volume 1 (for each 100 ml)

Serum creatinine > 1.5 mg/dL or 4

eGFR* <60 mL/min/1.73m2(GFR40-60),4(GFR20-40),6(GFR<20)


JACC Vol. 44, No. 7, 2004

Total risk score SCr >25% or 0.5 mg/dL (%) Require dialysis (%)

≤ 5 7.5 0.04

6-10 14.0 0.12

11-16 26.1 1.09

≥ 16 57.3 12.6

CI-AKI risk scoring system


Prevention strategies of CI-AKI

Non-pharmacological

• Dose of contrast media

• Route of administration

• Type of contrast media

Pharmacological

• Volume expansion (Nacl VS NaHCO3 VS oral fluid)

• NAC

• Others agentsArkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University




Endothelin releaseProstaglandin dysregulation




AKI

Pathophysiology of CI-AKI




Endothelin release




AKI


↓Dose of CM Intravenous route

↓Osm of CM

Volume expansion

Prostaglandin dysregulation

NAC



Type of contrast media

Type AgentOsmolality

(mOsm/kgH2O)Iodine content

(mg I/mL)Ionization

High-osmolarIoxathalamate 2130 350 Ionic monomer

Diatrizoate 2000 370 Ionic monomer

Low-osmolar

Iobitridol 915 350 Non ionic monomer

Iopamidol 796 370 Non ionic monomer

Iohexal 780 350 Non ionic monomer

Iopromide 770 370 Non ionic monomer

Ioxaglate 600 320 Ionic dimer

Iso-osmolarIotrolan 320 300 Non ionic dimer

Iodixanol 290 320 Non ionic dimerArkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Dose of contrast media (grams iodine) and the risk of CI-AKI

Acta Radiol 2008 49: 658

CI-A

KI(%

)

0

7.5

15

22.5

30

Grams iodine/eGFR ratio

<1 ≥1

25

3


Dose of contrast media (Volume) and the risk of CI-AKI

J Am Coll Cardiol 2007; 50: 584-590

97% used iso and low osmolar : Average Iodine 350 mg/ml


Less (iodine) is More (protection)

• In all patients, only the minimum amount of contrast medium necessary to answer the clinical diagnostic question should be used.

• Use the lowest possible dose of contrast medium in patients at risk for CI-AKI.


Risk factors of CI-AKI

Eur Radiol (2011) 21:2527-2541Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Route of administration

Clin Exp Nephrol. 2013 Aug;17(4):441-79Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Route of administration

Journal of Nephrology, vol. 25, no. 3, pp. 290-301, 2012.

1

RR 0.68; 95% CI 0.50-0.92; 𝑃 = 0.01

RR 0.75; 95% CI 0.44-1.26; 𝑃 = 0.27

11 randomized controlled trials (RCTs) including 2,210 patients with intra-arterial route 7 RCTs including 919 patients with intravenous route

Use low osmolality contrast media

Intravenous route

Intra-arterial route


High Osm VS Low Osm contrast agent

Relative

Risk

of C

IN0.0

0.3

0.6

0.9

1.2

High Osm Low Osm

0.64

1.00

Radiology 1993; 188: 171- 178.

• Meta-analysis

• High Osm VS Low Osm

• 39 Trials - 5146 patients

• CI-AKI = ↑ SCr>0.5 at 24-48 hrs

• RR of low osm = 0.64 (CI= 0.48-0.8)


Patients with DM and SCr 1.3-3.5 mg/dL who underwent coronary or aortofemoral angiography

Iso-osm, non-ionic Iodixanol (Visipaque), N=74, mean contrast volume= 163 ml,

PTCA 17%

Low-osm, non-ionic Iohexol (Omnipaque), N=65, mean contrast volume= 162 ml,

PTCA 25%

N Engl J Med 2003, 348:491-499.

• Randomized, double blind, prospective, multicenter

• Primary endpoint: peak increase in serum creatinine concentration at 3 days after angiographyArkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

NEPHRIC Study Endpoint

N Engl J Med 2003, 348:491-499.

Diff

eren

ce o

f SC

r at D

3

0

0.15

0.3

0.45

0.6

Iodixanol (Iso-Osm) Iohexol (Low-Osm)

0.55

0.13

P=0.001


418 DM with CKD (eGFR <50 mL/min) patients who underwent CAG ± PCI

Iso-osm, non-ionic Iodixanol, N=215

Low-osm, non-ionic Iopamidol, N=213

• Randomized, double blind, prospective, multicenter

• Primary endpoint: CI-AKI= SCr >0.5 at D3Am Heart J. 2009 Nov;158(5):822-828.e3Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

• No beneficial effect of iso-osm over low-osm in high risk CI-AKI patients

Am Heart J. 2009 Nov;158(5):822-828.e3

P=NS

P=NS


Inconsistent beneficial effect of iso-osmolarity over low-osmolarity contrast agent

Evidence-Based Nephrology 2009. Edited by D. A. Molony and J. C. Craig.


Meta-analysis did not show beneficial effect of iso-osmolarity over low-osmolarity contrast agent

An increase of at least 25% in serum creatinine level

RR=0.8 (CI 0.61-1.04)

An increase of at least 0.5 mg/dL in serum creatinine level

RR=0.75 (CI 0.44-1.26)

Radiology: Volume 250: Number 1︱January 2009Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Recommendation from ESUR and KDIGO

• Using of CM with low or iso-osmolarity in patients with risk factors for CIN.

!

• Using either iso-osmolar or low-osmolar iodinated contrast media, rather than high-osmolar iodinated contrast media in patients at increased risk of CI-AKI




Endothelin release




AKI



↓Osm of CM

Volume expansion


NAC



Trials of prophylactic fluid therapy for prevention of CI-AKI

Evidence-Based Nephrology 2009. Edited by D. A. Molony and J. C. Craig.

• No beneficial effect of oral fluid or 0.45%NSS for prevention of CI-AKI


JAMA, 2004;291:2328-2334

Patients With Baseline Serum Creatinine >1.8 mg/dl who Underwent Contrast Exposure (Iopamidol in All)

N=137

5% Dextrose Sodium Chloride Hydration (154

mEq/L of Sodium Chloride) N=68

4.25% Dextrose Sodium Bicarbonate Hydration (154

mEq/L of Sodium Bicarbonate) N=69

Primary endpoint: increase in serum creatinine ≥25% within 2 days post-exposure

Rate IV :Bolus of 3 mL /kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure.


EndpointsSodium Chloride

N=59

Sodium Bicarbonate

N=60P value

Incidence of CI-AKI (%) 13.6 1.7 0.02

Change in eGFR (%) -0.1 8.5 0.02

JAMA, 2004;291:2328-2334Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

Saline + NAC N=118

Saline+NAC+vitC N=116

7 excluded

NaCl rate 0.5-1 ml/kg/hr 12 hrs before and after procedure

NaHCO3 rate 3 ml/kg/hr 1 hr before and 1 ml/kg/hr 6 hrs after procedure

9 excluded9 excluded

107 included into analysis



Circulation. 2007;115:1211-1217

Patients with eGFR< 40 ml/min/1.73m2,N=393

Excluded, N=42

Randomized, N=351

Bicarbonate + NAC N=117


Inci

denc

e (%

)

0

3

6

9

12

Increase SCr ≥ 25% Increase SCr ≥ 0.5 mg/dL Decrease eGFR ≥ 25%

10.311.2

10.3

0.90.91.9

9.2

10.89.9

Saline+NAC Bicarb+NAC Saline+NAC+vit C

Circulation. 2007;115:1211-1217

P=0.01 P=0.026 P=0.018


• Beneficial effect of Isotonic bicarbonate over isotonic saline remains inconclusive

Curr Opin Nephrol Hypertens 19:539–549

Trials of prophylactic fluid therapy for prevention of CI-AKI (isotonic bicarb VS isotonic saline)


Meta-analysis of NaCl VS NaHCO3

Ann Intern Med. 2009;151:631-638.Arkom Nongnuch, Renal Unit, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

• Either volume expansion regimen may be used.

• Isotonic NaCl intravenous regime of 1.0-1.5 ml/kg/h for at least 6 h before and after contrast medium administration.

• Isotonic NaHCO3 3 ml/kg/h for 1 h before contrast medium followed by 1 ml/kg/h for 6 h after.

• I.V. volume expansion with either isotonic sodium chloride or sodium bicarbonate solutions, rather than no i.v. volume expansion, in patients at increased risk for CI-AKI.

• Not using oral fluids alone in patients at increased risk of CI-AKI.



N-acetylcysteine (NAC) in CI-AKI

• In theory, NAC may have vasodilator and antioxidant effects.

• Adverse reaction are mild including anaphylactoid reaction.

• Dosage for prevention CI-AKI are very low comparing to dosage for acetaminophen intoxication.





Endothelin release




AKI



↓Osm of CM

Volume expansion


NAC


N Engl J Med. 2000 Jul 20;343(3):180-4.

83 Patients with CKD (SCr 2.4±1.3 mg/dL) undergoing CT scan with low osmolality contrast

41 patients received NAC 600 bid 2 days (oral) + 0.45%Nacl 1ml/kg/hr 12 hrs before and

after procedure

42 patients received 0.45%Nacl 1ml/kg/hr 12 hrs before and

after procedure

Endpoint : Change in SCr at 48 hrs Incident of CI-AKI (↑SCr>0.5 mg/dL in 48 hrs)


N Engl J Med. 2000 Jul 20;343(3):180-4.

-7.5

0

7.5

15

22.5

30

Change in SCr at 48 hrs (mg/dL) CI-AKI

21

0.2 2

-0.4

Nac+hydration Hydration

P=0.01

P<0.001


N Engl J Med 2006;354:2773-82.

354 Patients admit for STEMI undergoing angioplasty

Control: 119 patients received 0.9% NaCl 0.5-1 ml/kg/hr for

12 hrs

Standard NAC: 115 patients received 0.9% NaCl 0.5-1 ml/kg/hr for 12 hrs + NAC 600 mg IV before and NAC 600 mg oral bid for 48

hrs after CAG ( Total NAC 3000 mg)

High dose NAC: 118 patients received 0.9% NaCl 0.5-1 ml/kg/hr

for 12 hrs + NAC 1200 mg IV before and NAC 1200 mg oral bid for 48

hrs after CAG ( Total NAC 6000 mg)


Inci

dent

(%

)

0

10

20

30

40

Increase SCr ≥ 25% Increase SCr ≥ 50% RRT Mortality

31

3

84

26

1511

5

18

33NaClStandard NACHigh dose NAC

N Engl J Med 2006;354:2773-82.

P<0.001

P<0.001

P=0.04 P=0.007


Endpoint : ↑SCr ≥ 25% or 50% in 72 hrs Incident of CI-AKI (↑SCr>0.5 mg/dL in 72 hrs)

J Am Coll Cardiol 2007;49:1283-8

111 Patients admit for ACS undergoing angioplasty

5% glucose isotonic NaHCO3 + NAC 2400 mg IV 5 ml/kg/hr for 1 hr before and NaHCO3 1.5 mg/kg/hr for 12 hrs + NAC 600 mg oral bid for 1

day (N=56)

0.9% NaCl 1 mg/kg/hr 12 hrs+ NAC 600 mg oral bid for 1 day after procedure (N=55)


Inci

dent

(%

)

0

10

20

30

40

Increase SCr ≥ 25% Increase SCr ≥ 50% CI-AKI

21.8

14.5

30.9

1.801.8

HCO3+NAC NaCl+NAC

J Am Coll Cardiol 2007;49:1283-8

P<0.0001

P=0.003 P=0.0009


Trials of prophylactic NAC therapy for prevention of CI-AKI


Meta-analysis NAC for CI-AKI

JACC: CARDIOVASCULAR INTERVENTIONS, VOL. 2, NO. 11, 2009


Other agents (not show benefits)

• Theophylline : Adenosine antagonist

• Fenoldopam : Selective dopamine A1 agonist

• Statin : Antioxidant and inflammation effects

• Hemodialysis and hemodiafiltration : remove radiocontrast agents


• Efficacy of NAC and other drugs in reducing the incidence of CIN remains unproven and their use cannot be recommended.

!

• Using oral NAC, together with i.v. isotonic crystalloids, in patients at increased risk of CI-AKI.

• Not using theophylline, fenodopam, and statin to prevent CI-AKI

• Not using prophylactic intermittent hemodialysis (IHD) or hemofiltration (HF) for contrast-media removal in patients at increased risk for CI-AKI



Future Directions !!! Personal with fluid administration

• Bioimpedance vector analysis (BIVA). JACC Vol. 63, No. 14, 2014

• RenalGuard System. REMEDIAL IItrial, Circulation. 2011;124:1260-1269

• Left ventricular end-diastolic pressure-guided volume expansion. POSEIDON trial, Lancet 2014; 383: 1814-23


Calculate eGFR, access risk of CI-AKI

eGFR<30 mi/min eGFR 30-59 mi/min eGFR>60 mi/min

Hold Metformin, NSAID, ± ACEI or ARB, Continue statin

• Isotonic NaCl or HCO3 ✦1-1.5 ml/kg/hr for 3-12 hrs pre and 6-24 hrs post

• Low osmolal contrast (Iso osmolal if high risk)

• Limited contrast volume • Consider NAC 600-1200 mg PO bid pre and post procedure 24 hr

• Isotonic NaCl or HCO3 ✦1-1.5 ml/kg/hr for 3-12 hrs pre and 6-24 hrs post

• Low osmolal contrast (Iso osmolal if high risk)

• Limited contrast volume • Consider NAC 600-1200 mg PO bid pre and post procedure 24 hr

• Nephrology consultation

Best clinical practice

• Monitor SCr at 48-72 hrs

• Define cause of AKI (not just contrast)

• Rechallenge ACEI or ARB, metformin !


Take Home Message

• Rethinking before using radio contrast

• Recognise patients at risk and evaluate risk of CI-AKI is crucial step of care

• Hydration when appropriated and may add NAC for prevention CI-AKI

• CI-AKI is common, differential diagnosis with cholesterol emboli

Ci aki for nst 2015

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