CONTRAST-INDUCED NEPHROPATHY

I. Pathophysiology

  1. Redunction in renal function following IV administration of  radiocontrast agents
  2. Thought to be due to a direct toxic effect on tubular epithelial cells

II. Risk factors (sources include J. Am. Coll. Cardio. 44:1393, 2004--JW)

  1. Pre-existing renal failure
  2. Hypotension
  3. Heart failure
  4. Advanced age
  5. Anemia 
  6. Diabetes mellitus
  7. Use of a high volume of contrast material

Preventive approaches:

  1. Adequate hydration
    1. In a randomized trial of 199 pts with serum Cr > 1.1 mg/dL randomized to NaCl vs. NaHCO3 (154 mEq/L of either) before and after administration of the IV contrast material iopamidol, incidence of (rise of 25% of more in serum Cr within 2d of contrast administration) was seen in sig. fewer NaHCO3 pts (1.7% vs. 13.6%) (JAMA 291:2328, 2004--abst)
  2. Hydration with sodium bicarbonate
    1. In a randomized trial of 119 pts undergoing contrast-requiring procedures and baseline serum Cr > 1.1 mg/dL, randomized to NaHCO3 vs. NaCl 3mL/kg IV 1h before contrast administration and 1mL/kg during and for 6h after the procedures, the NaHCO3 group had sig. lower incidence of contrast-induced nephropathy (defined as a 25% or greater increase in serum Cr < 48h after contrast administration) (JAMA 291:2328, 2004--JW)
  3. Hemofiltration
    1. Hemofiltration (1 liter/h fluid replacement) starting 4-8h before contrast administration and continuing 18-24h after completion of procedure, c/w isotonic saline hydration, was ass'd with sig. lower in-hospital mortality (2% vs. 14%), 1y mortality (10% vs. 30%), sig. lower frequency of (increase of serum Cr > 25% over baseline) (5% vs. 50%) and sig. less frequent need for temporary renal-replacement therapy (hemodialyssi of hemofiltration) (3% vs. 25%) in a randomized study of 114 pts with chronic renal failure (serum Cr > 2.0mg/dL) undergoing coronary angiography (NEJM 349:1333, 2003--abst)
  4. Oral N-acetylsyceteine
    1. In a randomized trial in 83 pts with serum Cr > 1.2mg/dL or CrCl < 50mL/min underoing elective CT w/IV contrast, N-acetylcysteine 600mg PO BID on the days before & after and after the procedure, c/w placebo, was ass'd with sig. lower incidence of > 0.4mg/dL increase in serum Cr at 48h (2% vs. 21%); no sig. adverse effects observed (NEJM 343:180, 2000--JW)
    2. In a randomized trial in 200 pts with serum Cr > 1.2mg/dL or CrCl < 60mL/min undergoing elective coronary angiography, randomized to N-acetylcysteine 600mg PO BID vs. placebo on thh day before the procedure, N-acetylcysteine was ass'd with sig. reduced incidence of > 25% increase in serum Cr at 48h (4% vs. 12%); mean increase in CrCl at 48h c/w baseline was sig. greater in N-acetylcysteine group.  Mean hospital stay sig. shorter w/acetylcysteine (0.9 vs. 2.0d) (JAMA 289:553, 2003--JW)
    3. In a meta-analysis of 7 RCTs of acetylcysteine vs. placebo for prevention of contrast nephropathy, acetylcysteine was ass'd with RR 0.44 for nephropathy (Lancet 362:598, 2003--AFP)
      In a study in 352 pts with acute MI undergoing primary angioplasty, randomized to N-acetylcysteine (600mg IV then 600mg PO BID x 2d), N-acetylcysteine (1200mg IV then 1200mg PO BID x 2d), incidence of contrast-induced nephropathy was sig. lower in both active tx groups (15% and 8% vs. 33% w/placebo, respectively as was incidence of in-hospital mortality (4% and 3% vs. 11% w/placebo, respectively).  (NEJM 354:2773, 2006--JW)
  5. Fenoldopam (click on link for pharmacologic information)
    1. 315 pts (mean age 70yo, 49% w/DM) with CrCl < 60mL/min underoing coronary angiography randomized to fenoldopam (target dose 0.1ug/kg/min) starting 1h before and continued until 12h after catheterization vs. placebo; about half of both groups received N-acetylcysteine.  No sig. diff. in incidence of increase in serum Cr > 25% from 24-96h after completion of administration or 30d incidence of death, dialysis, MI, or rehospitalization ("CONTRAST" study--JAMA 290:2284, 2003--JW)