Some radiology procedures require the use of a contrast material. The contrast may be called radiopaque because it can be seen on x-rays. Dye is injected into the patient's vein as a safe and effective way of visualizing organs and vessels of the body. Radiology procedures that use IV dye include coronary angiography, computed tomography scan, and intravenous pyelogram (Merten et al., 2004).

Complications from the use of IV dye may include allergic reaction or kidney damage. Contrast-induced nephropathy (CIN) is defined typically as a fixed rise in serum creatinine levels of 25% over baseline, or an absolute increase of at least 0.5 mg/dL within 48 hours after exposure to contrast medium that is maintained for 2-5 days and can not be attributed to other causes. Normal levels of creatinine are approximately 0.70-1.20 mg/dL. Age, gender, and body composition influence serum creatinine, making it an inaccurate gauge of kidney function. A more accurate measure of kidney function is creatinine clearance or glomerular filtration rate (Barrett & Parfrey, 2006). The Cockcroft-Gault formula is useful for calculating creatinine clearance based on a patient's age, gender, weight, and race.

Prevention of CIN is imperative as it influences morbidity and mortality rates significantly in hospitalized patients (Marenzi et al., 2006). CIN is the third most common cause of acute renal failure in hospitalized patients, after surgery and hypotension (Nash, Hafeez, & Hou, 2002). Contrast causes damage by impairing blood flow to the renal cortex and medulla. First, it stimulates vasoconstriction and decreases local prostaglandin-mediated and nitric oxide-mediated vasodilation. Second, contrast has an osmotic effect that leads to increased pressure within the renal interstition contributing to ischemia. Finally, it generates cytotoxic free radicals that cause direct renal tubular damage (Tadhg & Bulugahapitiya, 2004).

In CIN, serum creatinine peaks 3 days after administration of the medium. This effect usually is temporary, with the creatinine returning to its original value within 10 days after administration. Significant nephropathy is not likely to develop if the serum creatinine level does not escalate by more than 0.5 mg/dL over a 24-hour period (Barrett & Parfrey, 2006).

Risk Factors

Patients with pre-existing renal disease or a creatinine clearance less than 50 ml/min/1.73 [m.sup.2] are at risk for CIN. Renal function also is influenced by other factors, such as vascular disease, surgery, diabetes, age over 75, dehydration, heart failure, cirrhosis, or nephrosis. In addition, undergoing two contrast assays within 72 hours predisposes an individual to CIN. Other individual risks include hypertension, proteinuria, current use of NSAIDs or other nephrotoxins, and intra-arterial injection of contrast. Contrast medium delivered at high doses also will increase the risk of renal dysfunction (Barrett & Parfrey, 2006).

Prevention

Protection against CIN should be considered in patients with a serum creatinine greater than or equal to 1.5 or a glomerular filtration rate less 60 mL/min (Barrett & Parfrey, 2006). Careful deliberation is necessary for the radiologist performing the dye assay. Contrast that is non-ionic and iso-osmolar to human plasma at the lowest dye load is the best protection against CIN. Alternative studies using C[O.sub.2] angiography in the high-risk patient prevent the development of CIN. However, this option is not available to cardiologists, neurointerventionalists, or those administering CT studies. The simplest method of preserving renal function is to ensure adequate hydration. The patient at high risk for CIN should receive 0.9% saline intravenous infusion at 1 ml/kg/hour, adjusted for current fluid status and cardiovascular condition. This infusion should begin 6-12 hours before the procedure and continue for 12-24 hours after the contrast study if there is an appropriate diuresis to the addition of fluids (Merten et al., 2004).

The oral antidiabetic agent metformin (Glucophage[R]) causes acidosis which augments the toxic effects of free radicals that are produced by contrast dye. Because these free radicals can cause renal tubular damage, the patients must discontinue metformin 48 hours prior to dye procedure and only resume the drug when it is certain that CIN has not occurred (Schweiger et al., 2007).

Figure 1.

Contrast-Induced Nephropathy Can Be Prevented

What Is Contrast-Induced Nephropathy?

Did you know that contrast-induced nephropathy (CIN) is the third
leading cause of all cases of hospital-acquired renal failure?
According to recent studies, CIN is associated with a greater risk
of in-hospital morbidity and mortality, prolonged hospitalization,
increased health care costs, and potentially irreversible reduction
in kidney function.

CIN is defined most commonly as acute renal failure occurring
within 48 hours of exposure to intravascular radiographic contrast
material that is not attributable to other causes (a fixed rise in
serum creatinine of 25% over baseline or an increase of at least
0.5 mg/dL within 48 hours after exposure to contrast medium that is
maintained for 2-5 days). Significant nephropathy is not likely to
develop if the creatinine does not increase by more than 0.5 mg/dL
in a 24-hour period. At this point, the pathophysiology is not
clearly understood, yet some steps can be taken to prevent or lower
the risk of CIN.

Normal Levels of Creatinine = ~ 0.70-1.20 mg/dL

* Creatinine (CRT) clearance or glomerular filtration rate (GFR) is
a more accurate measure of kidney function.

* Cockcroft-Gault formula is useful for calculating creatinine
clearance based on a patient's age, gender, weight, and race.

Risk Factors for CIN

* Pre-existing renal disease

* CRT clearance <50 ml/min/1.73m2

* Vascular disease

* Surgery

* Diabetes

* Age over 75

* Dehydration

* Heart failure

* Cirrhosis or nephrosis

* Two contrast studies within 72 hours

* Hypertension

* Proteinuria

* Current use of NSAIDs

* Intra-arterial injection of contrast

* Contrast medium at high doses

When Do We Think about Prevention?

* When serum creatinine is [greater than or equal to] 1.5 or a GFR
<60 mL/min

* Best protection against CIN is for radiologists to use contrast
that is non-ionic and iso-osmolar to human plasma at the lowest dye
load or to use alternative studies using CO2 angiography in
high-risk patients.

* The simplest method for CIN prevention is ensuring adequate
hydration with IV 0.9% saline infusion at 1 mL/kg/hr, adjusted for
current fluid status and cardiovascular condition. This should
begin 6-12 hours before dye procedure and continue 12 -24 hours
after the contrast study.

What Else Do You Need to Know about CIN?

* Metformin is an oral diabetic agent that causes acidosis which
augments the toxic effects of free radicals produced by contrast
dye and results in renal tubular damage. Therefore, patients must
stop metformin 48 hours prior to dye procedure and not take it
until it is certain that CIN has not occurred.

* N-acetylcysteine 600 mg twice daily, plus hydration, before and
after exposure to contrast medium, offers significant protection
against CIN.

* The administration of sodium bicarbonate (3 mL/kg per hour for 1
hour before contrast followed by an infusion of 1 ml/kg per hour
for 6 hours after the procedure) with hydration using sodium
chloride is superior in preventing contrast-induced renal failure
when compared to hydration with sodium chloride alone.

Along with hydration, N-acetyl-cysteine (Mucomyst[R]) 600 mg twice daily before and after exposure to a contrast medium offers significant protection against CIN. This is related to its ability to scavenge oxygen-free radicals, thereby preventing direct oxidative tissue damage, and to its ability to counteract renal vasoconstriction induced by dye (Marenzi et al., 2006). Its protective effects also may relate to its ability to attenuate the cytotoxic effects of the contrast, as well as its vasodilatory effects on the renal arterioles by stimulating nitric oxide synthase.

Contrast media are believed to create free radicals by removing an electron from molecules. Free radicals are reactive molecules that cause damage by disrupting cell membranes. Because this process is promoted by an acidic environment but is inhibited by a higher pH, alkalinization of renal tubular fluid might be beneficial by reducing the levels of pH-dependent free radicals. One study compared the administration of sodium bicarbonate (3 mL/kg per hour for 1 hour before contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure) with hydration using sodium chloride. Hydration with sodium bicarbonate given before contrast exposure was superior in preventing contrast-induced renal failure when compared to hydration with sodium chloride. Volume supplementation with sodium bicarbonate plus N-acetylcysteine also has better efficacy in preventing contrast-induced nephropathy in patients at medium-to-high risk when compared to normal saline combined with N-acetylcysteine with or without the addition of ascorbic acid (Briguori et al., 2007).

Nursing Implications

Knowledge of the current therapies approved for prevention of CIN is essential in the care of patients undergoing procedures that use potentially nephrotoxic agents (see Figure 1). Nurses have vital roles in assessing patients for appropriate therapy, as well as providing timely interventions which may reduce procedure-associated complications and optimize treatment efficacy. Additionally, providing patient education regarding interventions facilitates patient understanding and adherence to recommended therapies. Nurses can ensure that lab work is current and follow-up assays are ordered. It also is very important to monitor strict intake and output on patients who have had studies with contrast dye.

References

Barrett, B., & Parfrey, R (2006). Preventing nephropathy induced by contrast medium. New England Journal of Medicine, 354(4), 379-386.

Briguori, C., Airoldi, R, D'Andrea, D., Bonizzoni, E., Morici, N., Focaccio, A., et al. (2007). Renal insufficiency following contrast media administration trial (REMEDIAL): A randomized comparison of 3 preventive strategies. Circulation, 115, 1211-1217.

Marenzi, G., Assanetli, E., Marana, I., Lauri, G., Campodonico, J., Grazi, M., et al. (2006). N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. New England Journal of Medicine, 354(26), 2773-2782.

Merten, G.J., Burgess, W.P., Gray, L.V., Holleman, J.H., Roush, T.S., Kowalchuk, G.J., et al. (2004). Prevention of contrast-induced nephropathy with sodium bicarbonate: A randomized controlled trial. JAMA, 291, 2328-2334.

Nash, K., Hafeez, A., & Hou, S. (2002). Hospital-acquired renal insufficiency. American Journal of Kidney Diseases, 39(5), 930-936.

Schweiger, M.J., Chambers, C.E., Davidson, C.J., Zhang, S., Blankenship, J., Bhalla, N.P., et al. (2007). Prevention of contrast induced nephropathy: Recommendations for the high risk patient undergoing cardiovascular procedures. Catheterization and Cardiovascular Interventions, 69, 135-140.

Tadhg, G.G., & Bulugahapitiya, S. (2004). Contrast-induced nephropathy. American Journal of Roentgenology, 183, 1673-1689.

Deborah Hallquist, MS, CRNP, RNFA, is a Nurse Practitioner, VA Medical Center, Philadelphia, PA.