A number of risk factors for contrast-induced nephropathy have now been identified through the analysis of information from large databases. Most of the data come from the cardiac literature and involve patients diagnosed with and without interventional procedures. The clinical risk factors correspond to recognized pathophysiological mechanisms of acute renal failure (Table 1).

  • Baseline renal insufficiency
  • Diabetes mellitus with renal insufficiency
  • Volume depletion
  • Hypoalbuminemia
  • Hypotension (mean arterial pressure < 100 mm Hg)
    • Intra-aortic balloon pump dependent
    • Urgent catheterization
  • Low-output class IV heart failure
  • Concomitant exposure to other nephrotoxins (nonsteroidal anti-inflammatory drugs and cyclosporin A)
  • Multiple contrast injections within 72 hours
  • Intra-arterial injection site
  • High volume of contrast
  • Type of contrast
Table 1. Risk factors for contrast-induced nephropathy.

The most important risk factor is chronic kidney disease. The National Kidney Foundation has staged chronic kidney disease (Table 2). The glomerular filtration rate (GFR) is the yardstick by which the various stages are defined because the GFR reflects kidney function. The serum creatinine is derived from the GFR. Because of marked differences in the production of creatinine among individuals, a given serum creatinine level will not reflect the same GFR across individuals. Since measuring the GFR (estimated using creatinine clearance) is tedious, inaccurate because of collection errors, and thus clinically inappropriate for the vast majority of patients, formulas have been developed to determine the estimated GFR (eGFR) based on the serum creatinine level. These formulas have been based on work with large groups of patients, with GFR measured via iothalamate clearance and validated for a number of different types of patients. The Modification of Diet in Renal Disease formula is the most widely accepted; it has the advantage that only the patient’s age, gender, race, and serum creatinine are required for the calculation. 1 Calculators are available on Web sites 2-5 and are also distributed by a number of organizations as a slide rule. Many authorities agree that the risk of contrast-induced nephropathy (CIN) increases as the eGFR falls below 60 mL per min per 1.73 m 2 (stage III).

    1 Chronic kidney damage with normal or elevated GFR     > 90
    2 Mildly decreased GFR     60 to 89
    3 Moderately reduced GFR     30 to 59
    4 Severely reduced GFR     15 to 29
    5 Kidney failure     < 15 or dialysis
Table 2. National Kidney Foundation-Kidney Disease Outcome Quality Initiative staging classification of chronic kidney disease; GFR=glomerular filtration rate.

Reduction in blood flow to the kidney will also enhance the risk of CIN. This occurs with hypotension (from any cause) and with intravascular volume depletion due to trauma, acute gastrointestinal losses, chronic use of diuretics, congestive heart failure, and cirrhosis. Pharmaceuticals such as nonsteroidal anti-inflammatory drugs may also contribute to a reduction in renal blood flow.

Procedure-related risk factors involve the contrast agent itself: its chemical characteristics (osmolality, ionicity, viscosity, and similar factors); the volume administered; and timing. The route of administration may also be important, although compelling evidence for a lower rate of CIN with intravenous (IV) use is not available.

Identifying high-risk patients is the first step in a programmatic approach to preventing CIN. A number of profiles have been developed to make the process more formula based.

Because the characteristics of patients undergoing coronary catheterization with percutaneous coronary intervention differ significantly from those of patients undergoing contrast-enhanced CT examinations, these profiles differ (Figure 1).

After the identification of high-risk patients, the next step is to determine whether the diagnostic information needed for their care can be obtained without the use of contrast. For some diagnostic questions, MR angiography with gadolinium chelates, interventional angiography with carbon dioxide, or ultrasound may be appropriate.

Figure 1. Identifying high-risk patients in CT use of contrast; eGFR=estimated glomerular filtration rate; EF=ejection fraction, NSAID-nonsteroidal anti-inflammatory drug, ACEI=angiotensin-converting enzyme inhibitor, and ARB=angiotensin receptor blocker. Adapted with permission from AJR Am J Roentgenol (reference #13)

When iodinated contrast is to be administered, efforts to protect the patient from the nephrotoxic effects of the contrast medium are required. Current recommendations are derived from randomized controlled trials, predominately in the cardiac literature. Volume expansion with diuresis (more than 150 mL per hour)6 is the most widely recommended therapy. There are a variety of approaches used in clinical trials that must be accommodated by clinical practice. In general, patients should not avoid oral intake unless this restriction is required by anesthesia administration; even then, the interval of intake restriction before contrast exposure should be as short as possible. IV fluids, in the form of 0.45% or 0.9% sodium chloride solution, should be started 12 hours before contrast exposure, if possible, at a rate of 1 mL per kg per hour. 7,8 The infusion, however, needs to be individualized to suit the clinical situation. For patients who are not in heart failure, a more rapid infusion augmented by oral water may suffice, although data are lacking concerning this. Isotonic sodium bicarbonate, infused at a rate of 3 mL per kg per hour for 1 hour before contrast exposure, was also shown to be effective in reducing the incidence of CIN. 9 This may be particularly useful in emergency situations and in patients with congestive heart failure. The use of diuretic agents (loop diuretics, mannitol, and dopamine) is discouraged because of either their lack of effect or their association with an increased risk of CIN. 8 IV fluids should be continued for 8 to 12 hours after contrast exposure at 1 mL per kg per hr.

At present, there is no role for the systemic administration of vasodilatory agents. Antioxidants such as N-acetylcysteine (NAC) and ascorbic acid have been effective in some, but not all, studies. The differences between studies may reflect differences in the dose, timing, and route of administration of NAC. Only one study 10 has reported on the use of NAC in patients with renal insufficiency receiving contrast-enhanced CT. The drug was effective when it was administered starting the day before exposure to contrast and was continued on the day of exposure.

The choice of contrast is also important. Low-osmolality and iso-osmolality contrast media are associated with a lower incidence of CIN, compared with high-osmolality contrast. There are too few head-to-head comparison trials to permit recommending one agent over another. 11 When contrast administration is combined with the prophylactic strategies of volume expansion and antioxidant therapy, the incidence of CIN is reduced for all agents. 12

The diagnosis of CIN can only be made if a second serum creatinine level is obtained 48 to 72 hours after contrast exposure. This is not an problem with hospital inpatients, but is difficult with outpatients. In high-risk patients, every effort should be made to obtain the follow-up serum creatinine level.

Richard Solomon, MD, is professor of medicine and chief of the Division of Nephrology, University Health Center, Fletcher Allen Health Care, Burlington, Vt.


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