Contrast-induced nephropathy

In medicine, contrast-induced nephropathy is acute kidney injury from radiocontrast. It is defined as either a greater than 25% increase of serum creatinine or an absolute increase in serum creatinine of 0.5 mg/dL.

Who is at risk?

Factors associated with an increased risk of contrast-induced nephropathy are:

• dose of radiocontrast more than 5 x body weight [kg])/serum creatinine
• preexisting renal insufficiency (such as Creatinine clearance < 60 mL/min [1.00 mL/s] - online calculator)
• preexisting diabetes
• reduced intravascular volume

A clinical prediction rule is available to estimate probability of nephropathy (increase =25% and/or =0.5 mg/dl in serum creatinine at 48 h):

Risk Factors:

• Systolic blood pressure <80 mm Hg - 5 points
• Intraarterial balloon pump - 5 points
• Congestive heart failure (Class III-IV or history of pulmonary edema) - 5 points
• Age >75 y - 4 points
• Hematocrit level <39% for men and <35% for women - 3 points
• Diabetes - 3 points
• Radiocontrast media volume - 1 point for each 100 mL
• Renal insufficiency:
  • Serum creatinine level >1.5 g/dL - 4 points

or

• Estimated Glomerular filtration rate (online calculator)

• 2 for 40–60 mL/min/1.73 m2
• 4 for 20–40 mL/min/1.73 m2
• 6 for < 20 mL/min/1.73 m2

Scoring:
5 or less points

• Risk of CIN - 7.5
• Risk of Dialysis - 0.04%

6–10 points

• Risk of CIN - 14.0
• Risk of Dialysis - 0.12%

11–16 points

• Risk of CIN - 26.1*
• Risk of Dialysis - 1.09%

>16 points

• Risk of CIN - 57.3
• Risk of Dialysis - 12.8%

Prevention

To minimize the risk for contrast-induced nephropathy, various actions can be taken if the patient has predisposing conditions. These have been reviewed in meta-analyses, although none of the meta-analyses include the more recent randomized controlled trial. A separate meta-analysis addresses interventions in for emergent patients with baseline renal insufficiency.

Choice of radiocontrast agent

Iso-osmolar, nonionic radiocontrast media may be the best according to a randomized controlled trial.

Hypo-osmolar, non-ionic radiocontrast agents are beneficial if iso-osmolar, nonionic contrast media is not available due to costs.

Hydration with or without bicarbonate

Randomized controlled trials of sodium bicarbonate

Study name or first author	Patients	Intervention	Primary outcomes			Conclusion
			Definition	Rate in control group	Rate in intervention group
Merten (2004)	119 patients with kidney disease (serum creatinine at least 1.1 mg/dL). Mean GFR was 41 mL/min per 1.73 m2	• 3 mL/kg per hour for 1 hour before contrast • 1 mL/kg per hour for 6 hours during and after contrast	> 25% rise in serum creatinine within 2 days	13.6%	1.7%	Bicarb is beneficial
REMEDIAL (2007)	219 patients with kidney disease (serum creatinine at least 2.0 mg/dL or GFR 40 mL/min per 1.73 m2 or less) undergoing coronary and/or peripheral procedures. All patients received NAC	• 3 mL/kg per hour for 1 hour before contrast • 1 mL/kg per hour for 6 hours during and after contrast Controls received isotonic saline: • 3 mL/kg per hour for 1 hour before contrast • 1 mL/kg per hour for 6 hours during and after contrast	> 25% rise in serum creatinine within 2 days	9.9%	1.9%	Bicarb is beneficial
Maioli (2008)	502 patients with kidney disease (creatinine clearance 60 mL/min per 1.73 m2 or less; mean GFR was 48 mL/min per 1.73 m2) undergoing coronary angiography All patients received NAC	• 3 mL/kg per hour for 1 hour before contrast • 1 mL/kg per hour for 6 hours after contrast Controls received: • isotonic saline 1 ml/kg/hr for 12 hours pre/post contrast	0.5 mg/dl rise in creatinine within 5 days	11.5%	10%	Bicarb is not beneficial
Brar (2008)	353 patients with kidney disease (GFR 60 mL/min per 1.73 m2 or less; mean creatinine clearance was 36 - 39 mL/min) undergoing coronary angiography or intervention	• 3 mL/kg per hour for 1 hour before contrast • 1.5 mL/kg per hour for 4 hours during and after contrast Controls received isotonic saline: • 3 mL/kg per hour for 1 hour before contrast • 1.5 mL/kg per hour for 4 hours during and after contrast	> > 25% fall in GFR within 4 days	14.6%	13.3%	Bicarb is not beneficial

Administration of sodium bicarbonate 3 mL/kg per hour for 1 hour before , followed by 1 mL/kg per hour for 6 hours after contrast was found superior to plain saline on one randomized controlled trial of patients with a creatinne of at least 1.1 mg/dL (97.2 µmol/L) . To make the solution, the study used 154 mL of 1000 mEq/L sodium bicarbonate to 846 mL of 5% dextrose. This is approximately three 50 ml ampules of bicarbonate in 850 ml of water with 5% dextrose. This was subsequently corroborated by a multi-center randomized controlled trial, which also demonstrated that IV hydration with sodium bicarbonate was superior to 0.9% normal saline. The renoprotective effects of bicarbonate are thought to be due to urinary alkalinization, which creates an environment less amenable to the formation of harmful free radicals..

Alternatively, one randomized controlled trial of patients with a creatinine over 1.6 mg per deciliter (140 µmol per liter) or creatinine clearance below 60 ml per minute used 1 ml/kg of 0.45 percent saline per per hour for 6-12 hours before and after the contrast.

Methylxanthines

Adenosine antagonists such as the methylxanthines theophylline and aminophylline, may help although studies have conflicting results. The best studied dose is 200 mg of theophylline given IV 30 minutes before contrast administration.

N-acetylcysteine

N-acetylcysteine (NAC) 600 mg orally twice a day, on the day before and of the procedure if creatinine clearance is estimated to be less than 60 mL/min [1.00 mL/s]) may reduce nephropathy.. A randomized controlled trial found higher doses of NAC (1200-mg IV bolus and 1200 mg orally twice daily for 2 days) benefited (relative risk reduction of 74%) patients receiving coronary angioplasty with higher volumes of contrast.

Since publication of the meta-analyses, two small and underpowered negative studies, one of IV NAC and one of 600 mg give four times around coronary angiography, found statistically insignificant trends towards benefit.

Some authors believe the benefit is not overwhelming. The strongest results were from an unblinded randomized controlled trial that used NAC intravenously. A systematic review by Clinical Evidence concluded that NAC is "likely to beneficial" but did not recommend a specific dose. One study found that the apparent benefits of NAC may be due to its interference with the creatinine laboratory test itself. This is supported by a lack of correlation between creatinine levels and cystatin C levels.

In one study 15% of patients receiving NAC intravenously had allergic reactions.

Prophylactic hemodialysis

Randomized controlled trials found benefit from prophylactic hemodialysis for patients with chronic kidney disease and a creatinine over 309.4 µmol/L (3.5 mg.dl) who have elective coronary catheterization, .

Other interventions

Other pharmacological agents, such as furosemide, mannitol, dopamine, and atrial natriuretic peptide have been tried, but have either not had beneficial effects, or had detrimental effects.