Preventive strategies

The strategies proposed to prevent CIN include the use of antioxidants, such as N-acetylcysteine (NAC), ascorbic acid, theophylline, and statins; low-osmolar contrast media; preventive renal replacement therapy; and periprocedural hydration with normal saline or sodium bicarbonate.

Regimens using various combinations of these measures have also been proposed. Preventive measures tested to date have shown conflicting data. While there is no evidence to support the use of ascorbic acid, theophylline, or statins to prevent CIN, the data on NAC are less clear-cut. The prophylactic role of NAC was first studied by Tepel et al in a randomized double-blinded study enrolling 83 patients with creatinine clearance less than 50 mL/min (N Engl J Med. 2000;343:180-184).

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Patients who received NAC (600 mg two doses before and after contrast administration) had a 2% incidence of CIN, while placebo-treated patients had a CIN incidence of 21%. However, more than 20 randomized, controlled trials report conflicting data. Eleven meta-analyses so far have produced mixed results.

Recently, a few smaller clinical trials reported the benefits of high-dose oral and IV NAC (1,200 mg two doses before and after contrast). Despite the varied findings, given its low cost, ease of administration, and lack of any associated harm, use of NAC in CIN prophylaxis might be justified.

Renal replacement therapy cannot be routinely advocated to prevent CIN. Lack of consistent benefit reported with hemodialysis/hemofiltration and the invasive nature of this approach remove it from consideration. Based on the available evidence, the American College of Cardiology recommends the use of iso-osmolar contrast medium in patients with CKD who undergo coronary vascular procedures. In patients who are at lower risk for CIN, low osmolar or isoosmolar contrast can be used.

Hydration is the best available intervention for preventing CIN. Volume expansion protocols to prevent CIN have undergone considerable change in the past 15 years. Earlier studies showed that IV hydration was superior to parenteral fluids. Mueller et al, who conducted the largest study using IV fluids, established the benefits of 0.9% sodium chloride over 0.45% sodium chloride (Arch Intern Med. 2002;162:329-336). Sodium bicarbonate decreases the acidification of urine in the renal medulla, which might reduce the generation of free radicals and protect the kidney from injury. Merten et al tested this hypothesis in a randomized controlled trial and reported additional benefit with sodium bicarbonate over normal saline (JAMA. 2004;291:2328–2334).

Several clinical trials comparing hydration with sodium bicarbonate and normal saline have been published in the past few years. Most trials used the protocol developed by Merten et al: 154 mEq/L of sodium bicarbonate 3 mL/kg/hr for one hour before contrast and then 1 mL/kg/hr for six hours after contrast. We conducted a meta-analysis of 12 trials that compared sodium bicarbonate to normal saline (Am J Kidney Dis. 2008; published online ahead of print). Pooled analysis showed that sodium bicarbonate (with or without NAC) significantly decreased the risk of CIN (odds ratio [OR] 0.46) without any significant difference in the need for renal replacement therapy (OR 0.50) or in-hospital mortality (OR 0.51) compared with normal saline (with or without NAC).

No increased risk of congestive heart failure or pulmonary edema with sodium bicarbonate-based therapy was noted. Publication bias favoring sodium bicarbonate therapy for the prevention of CIN was evident in our analysis, as was statistical heterogeneity. Since we completed our meta-analysis, two other clinical trials have shown no benefit with sodium bicarbonate over normal saline.

This scenario suggests that the evidence to support or refute the use of sodium bicarbonate in preventing CIN is still emerging, and we might have a better picture in the near future. Until then, given the lack of harm and potential benefit based on current available evidence, hydration with sodium bicarbonate may be used for CIN prophylaxis.

In any case, apart from minimizing the use of contrast media in high-risk patients, hydration with any IV fluids (normal saline or sodium bicarbonate) plus NAC should be used, as methods to prevent CIN in high-risk patients are underutilized in clinical practice.

Even though no randomized controlled trials have been conducted in the urological setting, these data can be extrapolated to urological settings in which contrast media is administered if the risk factors for CIN exist.

Dr. Navaneethan is a research associate in the Department of Nephrology and Hypertension, Glickman Urological & Kidney Institute, Cleveland Clinic, in Ohio.