contrast induced nephropathy - nyu langone health...of contrast-induced nephropathy and no...

Contrast Induced Nephropathy

O

CIAKI refers to an abrupt deterioration in renal function associated with the administration of iodinated contrast media

O

CIAKI is characterized by an acute (within 48 hours) ≥

0.3 mg/dL or ≥50% increase in

baseline SCr, or a reduction in urine output to <0.5 ml/kg per hour for more than 6 hours (Acute Kidney Injury Network)

Journal of Nephrology 2010; 23(04): 387-398

O

A more common definition is ≥0.5 mg/dL or ≥25% increase in baseline SCr within 3 days of intravascular CM exposure, in the absence of an alternative etiology

O

The SCr increase peaks between days 3 and 5 with levels usually returning to baseline within 1 to 3 weeks

Increasing riskO

Technological advances in imaging modalities, expanding imaging application

• cardiology patients undergoing invasive coronary angiography and/or PCI

• Interventional radiology patients undergoing different procedures

• patients from a variety of different specialties undergoing diagnostic CT

O

And an aging world population


Associated withO

increased morbidity and mortalityO

longer hospital staysO

higher rates of in-hospital events;O

higher rates of in-hospital 1-year and 5-year mortality


Risk factorsO

CKD particularly CKD combined with diabetes mellitus DM

O

Advanced age

O

Metabolic syndromeO

PrediabetesO

HyperuricemiaO

HypertriglyceridemiaO

Impaired fasting glucoseO

Gender (women ≥65 years of age are at greater risk than their male counterparts)

O

Intra-arterial contrast administration


Pathogenesis

O

Contrast media causes direct injury to the cells lining the renal tubule

O

The injury can be reproduced in vitro by incubating cells of the proximal tubule with contrast media

O

Cell death begins within minutes of exposureO

The contrast media is taken up into the cells and alters mitochondrial function resulting in generation of reactive oxygen species and apoptosis

Radiologic Clinics of North America Volume 47, Issue 5, September 2009

O

This injury is exacerbated by a simultaneous reduction in medullary blood flow that occurs in vivo resulting from vasoconstriction of the vasa recta

O

The medulla of the kidney has both very high oxygen consumption supporting active sodium transport and low tissue oxygen levels

O

Critical tissue hypoxia results following contrast media leading to additional damage of tubule cells within this region of the kidney

Radiologic Clinics of North America Volume 47, Issue 5, September 2009

Investigative Radiology Volume 45, Number 4, April 2010

Incidence

The American Journal of Cardiology Volume 98, 18 September 2006

Incidence in outpatientsO

A prospective, consecutive cohort (June 2007 through January 2009) of patients who received intravenous contrast for CECT in the emergency department of a large, academic, tertiary care center was enrolled

O

The incidence of CIN was 11% (70 of 633) among the 633 patients enrolled

O

Fifteen (2%) patients died within 45 d, including six deaths after study-defined CIN

O

Seven (1%) patients developed severe renal failure, six of whom had study-defined CIN

O

Of the six patients with CIN and severe renal failure, four died, and adjudicators determined that renal failure significantly contributed to all four deaths.

Mitchell et al. CJASN January 2010 Vol 5

ACE inh and ARBO

Four hundred twelve patients were included in a prospective, single-center study (January 2001–July 2004) to compare different treatments for CIN prevention

O

Creatinine levels within 72 h after CM application and in-hospital outcomes were documented

Kiski D et al. Nephrol. Dial. Transplant. 2010;25:759-764

Kiski D et al. Nephrol. Dial. Transplant. 2010;25:759-764

Prevention

Contrast mediaType of contrast

CONTRAST EXPOSURE

IncreasedViscosity

DirectVasoconstriction

IncreasedAdenosine

DIRECTCELLULARTOXICITY

ISCHEMIA

MitochondrialToxicity

CellVacuolization

Free Radical Formation

Depends onMonomer vsDimer forms

Depends onOsmolarity

Depends onIonization

Davidson et al (2006) Am J Cardiol 98(supp 6):42-58

Osmolarity

Circulation: Cardiovascular Interventions. 3(4):351-358, August 2010.

Circulation: Cardiovascular Interventions. 3(4):351-358, August 2010

Contrast Media Dose of contrast

O

Consecutive patients undergoing PCI were prospectively enrolled in the Dartmouth Dynamic Registry from 2000 to 2008 (n=10065)

O

Patients with preexisting dialysis-dependent renal failure were excluded (n=155)

O

Maximal acceptable contrast dose (MACD) was defined as (5 mL×body weight [kg])/baseline serum creatinine [mg/dL]

Circulation: Cardiovascular Interventions Volume 3(4), August 2010

Circulation: Cardiovascular Interventions Volume 3(4), August 2010

Final model included age, sex, body surface area, diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, priority of PCI, number of stents inserted, and baseline estimated glomerular filtration rate using MDRD equation

CONTRAST EXPOSURE

IncreasedViscosity

DirectVasoconstriction

IncreasedAdenosine

DIRECTCELLULARTOXICITY

ISCHEMIAMitochondrialToxicity

CellVacuolization

Free Radical Formation

Pre-Hydration

-N Acetyl Cysteine-Bicarbonate

-Dialysis

-Theophylline

Volume expansion

Group 1 subjects (n = 27) received 0.9% saline for 24 h at a rate of 1 ml/kg/h beginning 12 h prior to scheduled catheterization; and group 2 subjects (n = 27) were allowed unrestricted oral fluids

Nephron Clin Pract. 2003;93:C29–C34

A total of 1620 patients scheduled for elective or emergency coronary angioplasty were randomly assigned to receive isotonic (0.9% saline) (n = 809) or half-isotonic (0.45% sodium chloride plus 5% glucose) (n = 811) hydration beginning the morning of the procedure for elective interventions and immediately before emergency interventions.

IV fluids were started at a rate of 1 mL/kg of body weight per hour at

8 AM on the day of coronary angioplasty or immediately on arrival

in the catheter laboratory in case of emergency procedures.

After the

procedure, hydration was continued at 1 mL/kg of body weight

per hour until 8 AM the next morning.

Arch Intern Med.

2002;162:329-336

Bicarbonate

Zoungas S et al. Ann Intern Med 2009;151:631-638

N‐Acetylcysteine

Kelly A M et al. Ann Intern Med 2008;148:284-294

O

354 consecutive patients undergoing primary angioplasty were randomized to one of three groups:

• 116 patients were assigned to a standard dose of N-acetylcysteine (a 600-mg intravenous bolus before primary angioplasty and 600 mg orally twice daily for the 48 hours after angioplasty)

• 119 patients to a double dose of N-acetylcysteine (a 1200-mg intravenous bolus and 1200 mg orally twice daily for the 48 hours after intervention)

• 119 patients to placebo N Engl J Med 2006; 354:2773-2782

O

In a study presented at the American Heart Association's annual meeting 2,308 patients undergoing an angiographic procedure were randomized to 1,200 mg of N-acetylcysteine, prescribed orally twice daily, with two doses given before the procedure and two doses after the procedure, or to placebo

O

There was no difference in the primary end point of contrast-induced nephropathy and no difference in the secondary end point of serum creatinine elevations

Renal Replacement Therapy

O

It has been shown that dialysis removes contrast

O

However earlier trials have not been able to show any benefit to dialyze patients after administration of contrast

O

Dialysis was attempted at different times 1, 1.8 and 2 hours after contrast administration and in one study it was performed during the procedure itself

O

Some of those trials even showed worse kidney outcomes with dialysis

Dialysis Group (n = 42) Control Group (n = 40) p ValueAge (yrs) 65.3

±

11.1 65.9

±

11.2 0.780Male 27

(64%) 26

(65%) 0.946†Body weight (kg) 63.7

±

10.2 61.0

±

10.0 0.220Systemic hypertension 40

(95%) 37

(93%) 0.604†Diabetes mellitus 23

(55%) 25

(62%) 0.477†Coronary artery disease 0.600†Stenosis <50% 3 (7%) 1 (3%)Single-vessel 16

(38%) 12

(30%)Double-vessel 8 (19%) 10

(25%)Triple-vessel 15

(36%) 17

(42%)Prior myocardial infarction

10

(24%) 7 (18%) 0.481†

Left ventricular ejection fraction

0.45 ± 0.07 0.42 ± 0.08 0.221

Use of ACE inhibitors 11

(26%) 11

(28%) 0.894†Indication for CAG 0.812†Stable angina 22

(52%) 22

(53%)Acute coronary syndrome

20

(48%) 18

(47%)

Performed procedure 0.837†Coronary angiography 19

(45%) 19

(47%)Percutaneous coronary

intervention22

(55%) 21

(53%)

Volume of contrast medium (ml)

106.8

±

44.0 108.1

±

32.6 0.877

Journal of the American College of Cardiology Volume 50, Issue 11, 11 September 2007

O

All patients were given intravenous normal saline at 1 ml/kg/h for 6 h before and 12 h after contrast medium exposure, and then randomized to receive hemodialysis (dialysis group) or not (control group)

O

In the dialysis group, dialysis was started as soon as technically possible after angiography, and the time interval from contrast exposure to initiation of dialysis was recorded

O

The duration of dialysis was 4 hO

To lessen the hemodynamic changes, 200 ml normal saline priming was administered before dialysis and no fluid removal was prescribed in the dialysis group


Changes from baseline in the Cr level were significant at the peak value in the dialysis group (***p = 0.008) and on day 4, at the peak value, and at discharge in the control group (*p < 0.001); the difference between the 2 groups was significant on day 4 and at peak value (**p = 0.010 on day 4; p = 0.005 at peak value)


Marenzi et al. N Engl J Med. 2003 Oct 2;349

O

Patients were assigned to receive either hemofiltration therapy in ICU (hemofiltration group) or intravenous hydration with isotonic saline given in a step-down unit (control group)

O

For patients in the hemofiltration group, a treatment session was started 4 to 6 hours before the scheduled coronary procedure; treatment was resumed after the procedure was completed and continued for 18 to 24 hours

O

The flow of isotonic replacement fluid was set at a rate of 1000 ml per hour and was exactly matched with the rate of ultrafiltrate production, so that no net fluid loss resulted

O

Patients in the control group received a continuous intravenous infusion of isotonic saline at a rate of 1 ml per kilogram of body weight per hour for 6 to 8 hours before and 24 hours after the coronary procedure


Temporary renal-

replacement therapy was required in 25 % of the control patients and in 3 % of the patients in the hemofiltration group

The rate of in-hospital events was 9 % in the hemofiltration group and 52% in the control group (P<0.001)

In-hospital mortality was 2% in the hemofiltration group and 14% in the control group (P=0.02)

The cumulative one-year mortality was 10 % and 30%, respectively (P=0.01)


Controls (n = 30) Post-hemofiltration (n = 31) Pre/post hemofiltration (n = 31) P

value

Age (y) 71 ± 6 72 ± 8 72 ± 7 .86Men 22

(73%) 23

(74%) 20

(65%) .65Weight

(kg) 71 ± 8 73 ± 9 68 ± 7 .12Diabetes 12

(40%) 9 (29%) 7 (23%) .86Hypertension 18

(60%) 21

(68%) 23

(74%) .50Prior MI 8 (27%) 13

(42%) 10

(32%) .44Prior CABG 3 (10%) 5 (16%) 4 (13%) .77Prior PCI 2 (7%) 2 (6%) 1 (3%) .80Prior CHF 5 (17%) 9 (29%) 6 (19%) .47Mean LVEF (%) 47 ± 10 46 ± 12 48 ± 12 .66LVEF < 40% 9 (30%) 12

(39%) 8 (26%) .24Peripheral arterial disease 9 (30%) 9 (29%) 10

(32%) .96Cerebral vascular disease 4 (13%) 4 (13%) 5 (16%) .92COPD 5 (17%) 4 (13%) 4 (13%) .89Chronic atrial fibrillation 4 (13%) 3 (10%) 2 (6%) .66Aspirin 15

(50%) 19

(61%) 13

(42%) .31ACE inhibitor or ARB 9 (30%) 10

(32%) 8 (26%) .85Diuretics 17

(57%) 20

(64%) 18

(58%) .80Indication for angiographyStable angina 10

(33%) 8 (26%) 9 (29%) .81Recent MI 4 (13%) 7 (23%) 6 (19%) .64Unstable angina 9 (30%) 10

(32%) 8 (26%) .85Other 7 (23%) 6 (19%) 7 (23%) .92Serum creatinine (mg/dL) 3.6 ± 0.8 3.6 ± 0.7 3.7 ± 0.9 .85Creatinine clearance (mL/min)

20 ± 5 20 ± 4 18 ± 4 .12

Marenzi et al. Am J Med. 2006 Feb;119(2)

Patients were randomized in a 1:1:1 ratio to receive 1 of the following 3 prophylactic treatments: intravenous hydration with isotonic saline, performed for 12 hours before and for 12 hours after contrast agent exposure (control group)intravenous hydration with isotonic saline, performed for 12 hours before contrast agent administration, followed by hemofiltration treatment for 18 to 24 hours after contrast agent exposure (post-hemofiltration group)hemofiltration treatment performed for 6 hours before and for 18 to 24 hours after contrast agent exposure (pre/post-hemofiltration group)

Controls (n = 30)Post hemofiltration (n = 31)

Pre/post hemofiltration (n = 31)

p

value

Acute myocardial infarction

5 (17%) 4 (13%) 1 (3%) .21

Emergency CABG 0 (0%) 0 (0%) 0 (0%) -

Pulmonary edema requiring MV

1 (3%) 1 (3%) 0 (0%) .59

Cardiogenic shock requiring IABP

1 (3%) 0 (0%) 0 (0%) .35

Blood transfusion 4 (13%) 6 (19%) 5 (16%) .81

ARF requiring RRT 9 (30%) 3 (10%) 0 (0%) .002

≥2 clinical complications

6 (20%) 2 (6%) 0 (0%) .019

In-hospital mortality

6 (20%) 3 (10%) 0 (0%) .02


Weisbord, ASN renal week, Denver, Co November 2010

contrast induced nephropathy - nyu langone health...of contrast-induced nephropathy and no...

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