Contrast-induced nephrotoxicity (CIN) is a frequently encountered problem in modern medical practice. Incidence ranges from 2 to 38% in exposed individuals, depending on patient risk factors including elevation of baseline creatinine level and presence of diabetes mellitus.1
Contrast agents are responsible for 10% of all hospital-acquired renal failure cases.2
Acute renal failure (ARF) continues to be associated with a substantial inpatient mortality rate.2
One study showed that the difference in mortality between patients who did or did not develop ARF was 7 versus 34%.3
CIN is defined as an increase of serum creatinine level of 0.5 mg/dL or an increase of 25% or more above baseline.4
Occasionally, the onset of CIN will lead to a nonresolving ARF that requires dialysis, with an incidence of 0.7% in contrast-exposed patients.5
Complications associated with contrast administration are considered an “adverse drug reaction,” and have been shown to be a significant financial burden as well.6
In a randomized-controlled trial published in JAMA in 2004, intravenous hydration with solutions of sodium bicarbonate is more effective than using normal saline alone.7
This preventative measure is currently in use at our institution since 2005, and represents the standard of care.
Prostaglandin E1 (PGE1) is an endogenous vasodilatory mediator. It has been studied in vitro and in vivo in regards to prevention of CIN.8,9,10,11,12,13,14,15,16
In 1976, a study was conducted that used intra-arterial injection of PGE1 in human subjects who then underwent a contrast nephrogram. The result was a shorter time to the appearance of the contrast in the nephrogram, as well as an increased arterial diameter; both of which suggest an increase in renal blood flow.9
Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known to cause nephrotoxicity as a side effect. The likely mechanism of this is the inhibition of prostaglandin (PG) synthesis, and the resultant low levels of PG allows for unopposed vasoconstriction in the kidney; leading to hypoxic damage. Administration of a PGE1 analogue (misoprostol) can prevent/reverse the nephrotoxic side effects of NSAIDs.13
Hayashida et al found that patients under general anesthesia maintained a greater urine output with PGE1 administration compared with patients receiving placebo.8
Tabo et al studied PGE1 in patients undergoing hypotensive anesthesia. They concluded that creatinine clearance was preserved in the PGE1 group and was diminished in the control group.14
In this study, PGE1 outperformed several other proposed renal protective medications such as nicardipine, nitroglycerine, and sodium nitroprusside.
Due to the vasodilatory properties of PGE1, a hypothesized side effect is that it could induce hypotension, thus decreasing renal perfusion pressure and potentially worsening nephrotoxicity. Wutte et al tested this hypothesis in patients with terminal congestive heart failure. They found that even though there was a decrease in blood pressure, creatinine clearance was improved to a degree that achieved statistical significance.16
They concluded that the direct renal protective benefit outweighs any risk of diminishing renal function secondary to decreased perfusion pressure.
Other studies have established that PGE1 can provide renal-protective benefits even in the face of total renal ischemia. Vargas et al concluded that administration of PGE1 at the time of reperfusion (after total occlusion) ameliorates the expected renal injury, and that delayed treatment was not able to match those results.15
Paller and Manivel used an in vitro and in vivo rat model to demonstrate the renal-protective effects of PGE1.11
PGE1-treated rats had a threefold greater glomerular filtration rate than the control group. In addition, there was a direct “cytoprotective” effect found by using misoprostol in a model of renal toxic injury using mercuric chloride.
Paller studied the use of PGE1 in patients receiving cyclosporine, which is known to be nephrotoxic. Using a rat model, the results demonstrated a “substantial reversal” of renal dysfunction by the use of PGE1.12
This demonstrates that PGE1 is able to aid in renal protection from a non-NSAID, noncontrast toxin source. This suggests that PGE1 may be of benefit to all patients at risk for renal damage from a variety of causes.
Randomized-controlled clinical trials have likewise produced positive results for PGE1 use. In 2000, Koch et al studied 130 patients with a baseline creatinine level of at least 1.5. Either placebo or a variable dose of PGE1 was given before contrast administration. Postprocedure serum creatinine levels were significantly lower in the patients who received PGE1. There were no adverse reactions from intravenous (IV) PGE1 administration.10
Sketch et al conducted a similar study in 2001, again examining 130 patients with a baseline creatinine level of 1.5 or higher. Using a double blind, randomized, placebo-controlled design, they were able to reproduce the results of Koch et al, by concluding that PGE1 reduced the postprocedure elevation of creatinine level when compared with placebo (p
0.03). Additionally, the authors were able to establish that a dose of 20 μg/kg/min was the optimal dosage in their study.17
A large body of literature exists that has attempted to discover a preventative agent or strategy to reduce the incidence and severity of CIN. Past attempts at preventing CIN include use of advanced contrast agents, prophylactic hemodialysis, furosemide, N-acetylcysteine, sodium bicarbonate, IV hydration, calcium channel blockers, fenoldopam, nitroglycerin (NTG), and PGE1. This article reviews data from a prospective randomized trial involving PGE1 versus placebo combined with sodium bicarbonate and normal saline in a population of vascular surgery patients in an urban community hospital setting.