Induced Diuresis with Automated Hydration Therapy Reduces CIN

NEW ORLEANS, LA—Using a closed loop hydration monitoring and infusion system combined with low-dose furosemide was effective in reducing contrast-induced nephropathy (CIN) in high-risk patients, according to results of the REMEDIAL II trial.

REMEDIAL II was presented by Carlo Briguori, MD, PhD, of Clinica Mediterranea (Naples, Italy), during a late breaking clinical trials session April 4, 2011, at the American College of Cardiology Scientific Session/i2 Summit.

RenalGuard (PLC Medical Systems, Franklin, MA) is a closed-loop fluid management system that allows for high volume, diuretic-induced hydration with urine output monitoring. The system is designed to maintain intravascular blood volume and minimize the risk of over- or under-hydration during angiography. Data indicate that increasing periprocedural urine flow might help reduce the hepatotoxic effects of contrast media by diluting the contrast and more rapidly flushing it from the body, Dr. Briguori noted.

For REMEDIAL II, investigators at 4 interventional cardiology centers in Italy enrolled 292 patients with chronic kidney disease at high risk for CIN based on an estimated eGFR ≤ 30 ml/min/1.73 m2 and/or a Mehran score ≥ 11.

Study participants were scheduled for elective catheterization procedures and were randomly assigned to receive either conventional hydration with a combination of N-acetylcysteine (NAC) and sodium bicarbonate solution or hydration with normal saline plus NAC and low-dose furosemide (0.25 mg/kg) controlled by the RenalGuard system. Controlled hydration monitoring was started 1 hour before the procedure.

Urine Volume Up, CIN Down

Urine volume was significantly higher at 24 hours in the RenalGuard group (P < 0.001), with a mean urine flow in these patients of 352 ml/hour. Almost all patients (93%) met the urine outflow target of 300 ml/hour prior to the procedure.

The RenalGuard group had a CIN incidence rate (primary endpoint, defined as a serum creatinine [sCr] increase ³ 0.3 mg/dL at 48 hours) that was 53% lower than the control group. Several secondary endpoints were also improved with RenalGuard, including change in serum creatinine 48 hours after contrast exposure and changes in cystatin C at 24 and 48 hours (table 1).

Table 1. Primary and Secondary Endpoints

 

RenalGuard
(n = 146)

Control
(n = 146)

P Value

Rate of CIN at 48 hrs

11.0%

20.5%

0.025

Increase in sCr at 48 hrs ≥ 25%

2.7%

13%

0.001

Increase in sCyC at 24 hrs ≥ 25%

3.5%

10%

0.04

Increase in sCyc at 48 hrs ≥ 25%

8.5%

17%

0.039

Abbreviation: CI-AKI, contrast-induced acute kidney injury; sCr, serum creatinine; sCyC, serum cystatin C.

Notably, the trial also found that RenalGuard therapy significantly reduced the need for dialysis in high risk patients. In the control group, 4.8% of patients required some level of dialysis, compared to only 0.7% in the RenalGuard group (P = 0.031).

No differences were seen in the rates of death or pulmonary edema, although there was a hint of an increase in the latter in the RenalGuard group (0.7% for controls vs. 2.1% for RenalGuard; P = 0.62), something Dr. Briguori noted might be a concern. This risk, he said, might be avoidable by adjusting the aggressiveness of hydration based on filling pressures.

A New Strategy, or Beside the Point?

“According to the results of the REMEDIAL II trial, RenalGuard therapy, including hydration with normal saline plus a high dose of NAC and a limited dose of furosemide, should be considered as the prophylactic strategy for patients at high risk for CI-AKI,” Dr. Briguori said.

Asked by panelist John Hirshfeld, MD, of the University of Pennsylvania (Philadelphia, PA), whether the same results might be seen without RenalGuard, “just by being more aggressive in hydrating our patients before procedures,” Dr. Briguori said that it is very difficult to push such high levels of fluids—300 ml per hour and in some cases as high as 800 ml per hour—without monitoring output.

“And, in the past, giving just diuretics has had a deleterious effect,” Dr. Briguori said. “I think furosemide should be used only in a limited dose in order to push the kidney to increase urine flow, but after you reach this high flow, the machine maintains it without additional furosemide.”

He added that a major limitation of this system is that it cannot be used in STEMI patients where there is not enough time to establish high levels of urine flow.

Commenting on the trial, Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), told TCTMD, “What the REMEDIAL II study actually showed is what has been shown in the past, which is that if you hydrate the patient you can avoid acute kidney injury. And in this study not only was there adequate hydration, but they also had high urine output. Having said that, this was a small study and needs to be repeated in pivotal fashion with adequate power.” In short, more research is needed before the method can be used in everyday practice, she added.

The investigators used CIN as their primary endpoint, and while that is important, said Dr. Mehran “what one really wants to know is whether this strategy can be helpful in reducing important renal damage—chronic damage—not just acute injury. What was more valuable, in my opinion, was the decreased need for dialysis that they saw in this study.”

 


Source:
Briguori C, et al. REnal insufficiency following contrast MEDIA administration II trial (REMEDIAL II): RenalGuard system in high-risk patients for contrast-induced acute kidney injury. Presented: American College of Cardiology Scientific Session/i2 Summit; New Orleans, LA; April 4, 2011.

 

Related Stories:

Induced Diuresis with Automated Hydration Therapy Reduces CIN

NEW ORLEANS, LA—Using a closed loop hydration monitoring and infusion system combined with low dose furosemide was effective in reducing contrast induced nephropathy (CIN) in high risk patients, according to results of the REMEDIAL II trial. REMEDIAL II was presented
Disclosures
  • Dr. Briguori declared no conflicts of interest with regard to this study.
  • The study was funded by PLC Medical Systems, Inc.

Comments