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. A meta-analysis suggests "High-dose statins plus hydration with or without NAC might be the preferred treatment strategy to prevent contrast-induced". 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

The roles of sodium bicarbonate administration to prevent acute kidney injury is not clear according to a systematic reviews of randomized controlled trials. Heterogeneous, conflicting trial results may be due to publication bias with the smaller, less rigorous trials showing benefit.

A common regimen is three 50 ml ampules of bicarbonate in 850 ml of water with 5% dextrose. 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..

A meta-analysis is available, but does not include all the studies in the evidence table below.

Randomized controlled trials of sodium bicarbonate

Study name or first author	Patients	Intervention	Primary outcomes			Conclusion
			Definition	Rate in intervention group	Rate in controlgroup
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	1.7%	13.6%	Bicarb is beneficial
Masuda (2007)	59 patients undergoing emergent coronary angiography	• 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	>0.5 mg/dl or > 25% rise in serum creatinine within 2 days	7%	35%	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	1.9%	9.9%	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	10%	11.5%	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	13.3%	14.6%	Bicarb is not beneficial
Ueda (2011)	59 patients with kidney disease (GFR 60 mL/min per 1.73 m2 or less or creat > >1.1 mg/dl ; undergoing coronary angiography or intervention	• 3 mL/kg per hour for 1 hour before contrast • 154 mEq/L of sodium bicarbonate 0.5 ml/kg before contrast • 3 mL/kg per hour for 1 hour before contrast • 154 mEq/L sodium bicarbonate at 1 ml/kg/hour for 6 hours after contrast to both groups	> > 25% fall in GFR or >0.5 mg/dl rise serum creatinine level within 2 days	3.3%	27.6%	Bicarb bolus is beneficial

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. However, a more recent trial found no 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.

Ascorbic acid

Ascorbic acid may help according to a systematic review of randomized controlled trials.

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.