Contrast Induced Acute Kidney InjurySurendra Babu M2nd year resident Dept of Nephrology,NIMS

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.

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).

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.

Uniqueness of Contrast induced AKI

Universally iatrogenic Risk factors well characterised Time of insult largely predictable

Make it amenable to prevention

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.

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 19.4% in patients who did not develop CIN.

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

0 1 2 3 40

20

40

60

80

100

120

number of risk factorsArch Intern Med 1990;150

INCI

DEN

CE in

%

Left ventricular &-----: 30-45 mLaortic angiographyPCI-----------------------:150-200 mLCECT scan--------------:uses 100-150 mL IVU-----------------------:100-mL bolus of a 50%–60%

FFA uses Na fluorescein and not assoc with CIN

Contrast Induced AKI

Direct tubular toxicity

Oxidative stress

Vasoconstricti

on

Preventive strategies

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

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.

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.

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.

Isotonic v. hypotonic saline

Mueller C, et al. Arch Int Med. 2002; 162:329-336

P=0.04

P=0.35

P=0.93

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

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

Clin J Am Soc Nephrol 4: 1584–1592, 2009

Trials those who included patients with CKD2-4 as well as normal renal function.

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

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, 2009

Trials those who included patients with CKD2-4 as well as normal renal function.

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

NAC for CIAKI (n=83)

0%

5%

10%

15%

20%

25%

Tepel M, et al. N Engl J Med 2000; 343:180-184

% C

IN (S

cr ↑

0

.5 m

g/dL

@ 4

8h)

Control

2%

21%

P=0.01

NAC

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 

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

POSEIDON

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

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

Results total mean (SD) volume of NS administered was 1727

ml in LVEDP group vs 812 ml in control group

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

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.

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.

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.

KNOW PREVENTION , NO CIN

NO PREVENTION, KNOW CIN

Thank you