Hydration System May Thwart Contrast Nephropathy: REMEDIAL 2

April 05, 2011

April 5, 2011 (New Orleans, Louisiana) — For cutting the risk of contrast-induced nephropathy during catheterization, maybe the precision of aggressive hydration can be as important as what protective agents are added to the saline.

An infusion system that balances fluid intake with urine output during catheter procedures appears to help prevent acute renal toxicity from iodinated contrast agents, suggests a small randomized trial reported here at the American College of Cardiology (ACC) 2011 Scientific Sessions/i2 Summit.

The second Renal Insufficiency Following Contrast Media Administration Trial (REMEDIAL 2) randomized patients considered high risk for contrast-induced acute kidney injury to have their coronary- or peripheral-artery catheterizations--diagnostic, therapeutic, or a combination of the two--accompanied by sodium-bicarbonate–based hydration or hydration with the RenalGuard system (PLC Medical Systems). All procedures used the iso-osmolar contrast agent iodixanol (Visipaque, GE Healthcare).

Laboratory markers of renal injury were significantly less likely to be increased over 48 hours among RenalGuard-managed patients, who were also significantly less likely to go on dialysis within one month.

In his presentation of the trial, Dr Carlo Briguori (Clinica Mediterranea, Naples, Italy) described the device as "an automated hydration-matching system" that maintains high urine output (the target in the study was >300 mL/h) during use of contrast agents but avoids the negative fluid balance that can result from the high-dose furosemide diuresis used to facilitate urinary contrast elimination (which is thought to attenuate the risk of contrast renal toxicity).

In essence, the RenalGuard system--available in Europe but investigational in the US--aims to match fluid input to output and promote urination with only limited use of loop diuretics.

In the panel discussion following Briguori's presentation, Dr John Hirshfeld (University of Pennsylvania, Philadelphia) asked whether the input-output matching could be done conventionally without the RenalGuard "just by being more aggressive in hydrating our patients prior to the procedures."

Normal hydration procedures generally won't achieve such high urinary flow rates, Briguori replied. "You can reach 100 mL/h or 150 mL/h, but it's very difficult to reach 300 mL/h" and to avoid excess volume depletion, he said.

Speaking with heartwire , Dr Martin B Leon (Columbia University, New York, NY), who isn't connected to REMEDIAL 2, agreed that "in clinical practice we generally do not sustain a diuresis of 300 mL/h; that's pretty aggressive. So if they can do it safely by matching output with infusion, assisted with some [furosemide] Lasix, I think it's probably safer for the patient, and it does get you a reliable hydration that, I think, and as was shown by the trial, certainly may be effective in preventing contrast nephropathy."

Patients were eligible for REMEDIAL 2 if they had an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, a contrast nephropathy risk score >11, no pulmonary edema, and no recent exposure to contrast media.

The 146 controls received prophylactic sodium bicarbonate at 3 mL/kg IV one hour before and 1 mL/kg for six hours after their procedures, as well as high-dose N-acetylcysteine (NAC) 1200 mg orally twice daily for 48 hours and 1500 mg IV periprocedurally.

RenalGuard management in the other 146 patients was aimed at the >300-mL/h urine output target (reached by 93% of the group), at which time patients "were ready for their procedure." They also received furosemide at 0.25 mg/kg and NAC at 1.5 g/L.

There were no significant baseline or 48-hour differences between the two groups in eGFR, serum sodium or potassium, or serum urea nitrogen. Nor were there procedural differences, including proportions of solely diagnostic angiography, solely PCI, both, or peripheral intervention; or in volume of contrast used.

The primary end point, a serum creatinine increase of >0.3 m/dL within 48 hours of the procedure, was seen in 20.5% of controls and 11% of patients in the RenalGuard group, for an odds ratio of 0.47 (95% CI 0.24–0.92, p=0.025).

Laboratory Measures of Renal Function and Clinical Outcomes in REMEDIAL 2

Secondary end point Control, n=146 (%) RenalGuard, n=146 (%) p
Creatinine increase at 48 h      
>0.3 mg/dL 20.5 11 0.025
>0.5 mg/dL 15 6 0.003
>25% 13 2.7 0.001
Cystatin C increase at 48 h (%)      
>10 34 22 0.027
>15 25.5 16 0.050
>25 17 8.5 0.039
Major clinical events at 1 mo      
Death 4.1 4.1 1.0
Dialysis 4.8 0.7 0.031
Pulmonary edema 0.7 2.1 0.62
Total 9.6 6.8 0.52

RenalGuard patients also fared significantly better with respect to secondary end points reflecting renal injury at 48 hours and in rate of dialysis at 30 days.

Controls trended higher in rate of in-hospital dialysis (4.1% vs 0.7%, p=0.056) and had significantly higher serum creatinine (p=0.008) and cystatin C (p=0.004) at 48 hours.

Briguori pointed out that pulmonary edema was more common in the RenalGuard group, although the difference wasn't significant. Still, it's a problem that could potentially be avoided in the future, he said, by adjusting the aggressiveness of hydration and diuresis according to filling pressures.

Briguori declared that he has no "real or perceived" relevant conflicts of interest. Leon disclosed being an unpaid consultant for Abbott, Medtronic, and Boston Scientific. Hirshfeld disclosed receiving consulting fees or honoraria from St Jude Medical.

RenalGuard System