REMEDIAL II Published: New Therapy Prevents Contrast-Induced Kidney Damage

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A closed-loop hydration monitoring and infusion system combined with low-dose furosemide can help prevent contrast-induced acute kidney injury (AKI), according to a study published online August 15, 2011, ahead of print in Circulation.

Results from REMEDIAL II (Renal Insufficiency After Contrast Media Administration Trial II) were previously presented on April 4, 2011, at the American College of Cardiology Scientific Session/i2 Summit in New Orleans, LA.

For the multicenter study, Carlo Briguori, MD, PhD, of Clinica Mediterranea (Naples, Italy), and colleagues enrolled 292 patients scheduled for elective catheterization who had an estimated glomerular filtration rate (eGFR) no higher than 30 mL/min/1.73 m² and/or Mehran score of at least 11, indicating high risk of developing contrast-induced AKI. Subjects were randomized to receive either:

• Conventional hydration with a combination of oral N-acetylcysteine (NAC) and sodium bicarbonate solution (n = 146)
• Hydration with normal saline plus intravenous NAC controlled by low-dose furosemide and the RenalGuard system (n = 146; PLC Medical Systems, Franklin, MA)

Iodixanol (Visipaque; GE Healthcare, Buckinghamshire, United Kingdom) was the contrast agent used in all patients, at a volume of 145 ± 79 mL in the RenalGuard group and 135 ± 76 mL in the control group. The average total volume of intravenous hydration also was higher in RenalGuard patients than in controls (2,312 mL vs. 1,438 mL; P < 0.001).

AKI, Dialysis Risk Lessened

The primary endpoint of contrast-induced AKI (defined as ≥ 0.3 mg/dL increase in serum creatinine at 48 hours vs. baseline) was less prevalent in the RenalGuard group than in the control group. Other outcomes, including changes in cystatin C at 24 and 48 hours as well as the rates of dialysis in-hospital and at 30 days, also favored RenalGuard therapy (table 1).

Table 1. Outcomes

Patients who developed AKI had significantly longer hospital stays than those who did not (10 ± 7 days vs. 6.5 ± 6.7 days; P = 0.008). They also showed a trend toward increased risk of death at 1 month (6.5% vs. 3.6%; P = 0.41).

Pulmonary edema, a concern during hydration, was numerically higher with RenalGuard vs. conventional treatment (2.1% vs. 0.7%; P = 0.62).

“The RenalGuard System, with its matched fluid replacement capability, enables the physician to achieve high urine output safely with a low furosemide dose by maintaining the intravascular volume and minimizing the risk of overhydration or underhydration,” the investigators write, concluding that controlled, forced diuresis with RenalGuard offers superior protection against contrast-induced AKI during catheterization.

Excitement in Spite of Caveats

In a telephone intrview with TCTMD, John W. Hirshfeld Jr, MD, of the University of Pennsylvania Medical Center (Philadelphia, PA), expressed both enthusiasm and reservations about the RenalGuard system.

“It is a hassle [to use],” he commented, so an obstacle to the therapy being readily adopted may be how much facilities want to compromise their work flow by putting it into place. “That being said, . . . [w]e certainly know that when you cause contrast nephropathy from contrast agent exposure, it’s a bad thing. It’s pretty clear that this is the most effective treatment to prevent contrast nephropathy that we have come up with to date.”

But in an e-mail communication, Dr. Briguori maintained that the system is not hard to use. The only downside to RenalGuard is the risk of pulmonary edema, he said, advising that “patients with very low LVEF and unstable hemodynamic conditions should be carefully evaluated before starting [the procedure].”

Dr. Hirshfeld said the key will be targeting which patients are most likely to benefit from RenalGuard, in whom the added trouble is worth the effort. Not only does the REMEDIAL II population represent a fairly “broad spectrum of severity of renal insufficiency,” but patients also were given a range of contrast agent doses, he added.

According to Dr. Hirshfeld, 2 other factors may have muddied the results. RenalGuard patients received intravenous NAC, which he said is rarely, if ever, used in clinical practice in the United States, while controls received oral NAC. In addition, RenalGuard patients were given nearly a liter more hydration fluid than controls.

Dr. Hirshfeld also questioned the choice of change in serum creatinine as the primary endpoint, pointing out that hydration alone can affect such measurements, though the effect may have disappeared by 48-hour follow-up. “It’s ambiguous,” he said. “The ideal thing would have been [to ask], what’s the creatinine 1 month later?”

Despite these caveats, Dr. Hirshfeld said, “it’s pretty hard to walk away from 7 patients getting dialysis vs. 1.” The huge remaining question, he noted, is whether the benefits of RenalGuard are maintained in the long term.

Dr. Briguori agreed. “We just started to assess whether the use of RenalGuard therapy may prevent further deterioration of renal function in patients with chronic kidney disease (eGFR < 30),” he reported.

Study Details

RenalGuard therapy began with an initial bolus of 250 mL normal saline infused over 30 minutes. After priming, furosemide (0.25 mg/kg) was administered intravenously to achieve optimal urine flow of at least 300 mL per hour. When urine flow reached its target, patients were moved into the catheterization lab. Controlled hydration and urine flow monitoring continued during the procedure and for 4 hours after its conclusion. Additional furosemide doses were used when urine flow decreased below the target.

 

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Source:
Briguori C, Visconti G, Focaccio A, et al. Renal Insufficiency After Contrast Media Administration Trial II (REMEDIAL II): RenalGuard system in high-risk patients for contrast-induced acute kidney injury. Circulation. 2011;Epub ahead of print.

 

 

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