麻豆传媒

ANAHEIM -- Neither sodium bicarbonate nor N-acetylcysteine (NAC) protect against kidney damage from contrast use with angiographic procedures in high-risk patients, the PRESERVE trial showed.

Serious adverse outcomes -- death, renal replacement, or persistent decline in kidney function -- rates at 90 days in the two-by-two factorial designed randomized trial were:

• 4.4% with sodium bicarbonate versus 4.7% with sodium chloride as a similarly isotonic control infusion (OR 0.93, 95% CI 0.72-1.22)
• 4.6% with NAC versus 4.5% with placebo (OR 1.02, 95% CI 0.78-1.33)

Nor was there any interaction between NAC and sodium bicarbonate for that primary endpoint (P=0.33) or difference between arms for contrast-associated acute kidney injury (AKI), Steven Weisbord, MD, of the VA Pittsburgh Healthcare System, reported at the American Heart Association meeting and simultaneously online in the New England Journal of Medicine.

“Modifying the type of intravenous fluid above and beyond what has really been considered the standard of care for 2 decades, that is isotonic saline, is not going to have an impact on hard outcomes,” he concluded at a press conference for the late-breaking clinical trial session. “This study really should now eliminate use of sodium bicarbonate as a fluid. And really even other fluids until they are looked at in large-scale clinical trials.”

These findings come amid controversy as none of the many strategies attempted to attenuate AKI, such as hydration, bicarbonate, and NAC, have definitively been shown to work, commented Robert Harrington, MD, of Stanford University in Stanford, California, who was not involved in the study.

Still, the idea that "urinary alkalinization and scavenging of reactive oxygen species mitigate renal tubular epithelial-cell injury from the use of iodinated contrast material" has caught on and both treatments are widely used in practice, Weisbord's group noted.

was the largest such trial by far, with 5,177 patients at high risk for renal complications scheduled for angiography, but had to be stopped early after a prespecified interim analysis suggested futility.

"This is a definitive finding," Peter McCullough, MD, MPH, of Baylor University Medical Center in Dallas, told 麻豆传媒. "The all-cause hospitalization in this study at 90 days was 42%, implying that there is a lot of recurrent hospitalization in this older group at risk for contrast-induced AKI. However, the reasons for hospitalization may not be related to the index event in the catheterization laboratory."

"In my view, what it means the future is we're on to novel strategies and novel treatments," added McCullough, who was not involved in the study. "We either need to develop a non-toxic contrast agent that is perfectly safe for the catheterization laboratory, with no consequences for the kidneys, or we need novel treatments that are organized to preserve and protect organs from the damage of contrast-induced injury to the cells as well as atheroembolism."

The trial randomized participants to receive IV 1.26% sodium bicarbonate or IV 0.9% sodium chloride and, in the other comparison, 5 days of oral acetylcysteine or oral placebo. Participants were mostly in the U.S. (35 of the 53 sites were VA centers) but also Australia, Malaysia, and New Zealand. They had to have stage 3 or 4 chronic kidney disease, with an estimated glomerular filtration rate (eGFR) of 15 to 44.9 mL/min/1.73 m² of body-surface area or, among those with diabetes mellitus, 45 to 59.9 mL/min/1.73 m².

Limitations included the potential that 90-day endpoint benefit could have been obscured by intervening events or that early transient decrements in kidney function could have been missed; the predominantly male population; and lack of a single IV administration protocol such that patients did not receive identical fluid volumes. Also, many participants got relatively small contrast volumes and without percutaneous interventions, which may have accounted for the lower- than-predicted event rates observed, the researchers suggested.

Nonetheless, they concluded that their "finding that the use of sodium bicarbonate and acetylcysteine did not reduce the incidence of our primary or secondary end points supports the strong likelihood that these interventions are not clinically effective in preventing acute kidney injury or longer-term adverse outcomes after angiography."

Study discussant Núria Pastor-Soler, MD, PhD, a nephrologist at the University of Southern California in Los Angeles, agreed that the limitations were fairly minor.

Sodium bicarbonate “is often harder to prepare for hospitals. It’s subject to having to be prepared onsite. So the fact that now we can go readily when patients are undergoing this procedure to the use of sodium chloride is important.”

Press conference moderator Eric Peterson, MD, of the Duke Clinical Research Institute in Durham, North Carolina, added that saline will probably even save some healthcare dollars. However, he was skeptical that clinical inertia would be quickly changed by the trial. “Our adoption pattern takes 17 years, our extinction pattern takes almost that same amount. So we’ll have to keep an eye on it.”

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