Meeting NewsPerspective

REMEDIAL III: Hydration guided by urine flow rate cuts contrast-induced acute kidney injury

Carlo Briguori

SAN FRANCISCO — A hydration regimen guided by urine flow rate was superior to a strategy guided by left ventricular end-diastolic pressure for reducing contrast-induced acute kidney injury in patients undergoing PCI, according to the results of the REMEDIAL III study.

For the investigator-initiated study, researchers randomly assigned 708 consecutive patients undergoing PCI who had chronic kidney disease and/or were at high risk for contrast-induced acute kidney injury to hydration with normal saline using a device (RenalGuard, RenalGuard Solutions Inc.) to assess urine flow rate or a regime based on left ventricular end-diastolic pressure (LVEDP).

The protocol for the device group was to reach a urine flow rate of at least 300 mL per hour before the procedure and to maintain a urine flow rate of at least 450 mL per hour during the procedure, while the protocol for the LVEDP group was to start hydration 1 hour before PCI and to adjust the hydration rate according to LVEDP during the procedure, Carlo Briguori, MD, PhD, chief of the laboratory of interventional cardiology at Mediterranea Cardiocentro in Naples, Italy, said during a press conference at TCT 2019. Both groups continued the regimen for 4 hours after the procedure, he said.

The primary endpoint of contrast-induced acute kidney injury or acute pulmonary edema occurred in 5.7% of the device group and 10.3% of the LVEDP group (RR = 0.56; 95% CI, 0.39-0.79; number needed to treat to prevent one event = 22), Briguori said.

“The urine flow rate-guided approach carried out by the RenalGuard system seems to be superior to the left ventricular-end-diastolic-pressure-guided regimen to prevent the composite of acute kidney injury and acute pulmonary edema in high-risk patients,” he said at the press conference. “A strict control of potassium balance is required during RenalGuard therapy.”

CKD was defined as an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or less. High risk for acute kidney injury was defined as Mehran’s score of at least 11 and/or Gurm’s score of more than 7. The mean age in both groups was 74 years. The device group consisted of 66% men and the LVEDP group consisted of 59% men.

In a panel discussion at the press conference, experts debated different approaches to prevent contrast-induced acute kidney injury.

“I take a different approach; I think we should just get rid of contrast,” Gary S. Mintz, MD, senior medical adviser for the Cardiovascular Research Foundation, said. “Ziad Ali, MD, has pioneered the concept of zero-contrast PCI. More than 90% of planned zero-contrast PCIs never require even 1 cc of contrast during the procedure. They are totally imaging-guided. And if you get rid of contrast, you get rid of contrast nephropathy.” – by Erik Swain

Reference:

Briguori C, et al. Late-Breaking Trials 4. Presented at: TCT Scientific Symposium; Sept. 25-29, 2019; San Francisco.

Disclosures: Briguori reports no relevant financial disclosures. Mintz reports he received consultant fees/honoraria/speaker fees from Boston Scientific, Terumo and Volcano.

Carlo Briguori

SAN FRANCISCO — A hydration regimen guided by urine flow rate was superior to a strategy guided by left ventricular end-diastolic pressure for reducing contrast-induced acute kidney injury in patients undergoing PCI, according to the results of the REMEDIAL III study.

For the investigator-initiated study, researchers randomly assigned 708 consecutive patients undergoing PCI who had chronic kidney disease and/or were at high risk for contrast-induced acute kidney injury to hydration with normal saline using a device (RenalGuard, RenalGuard Solutions Inc.) to assess urine flow rate or a regime based on left ventricular end-diastolic pressure (LVEDP).

The protocol for the device group was to reach a urine flow rate of at least 300 mL per hour before the procedure and to maintain a urine flow rate of at least 450 mL per hour during the procedure, while the protocol for the LVEDP group was to start hydration 1 hour before PCI and to adjust the hydration rate according to LVEDP during the procedure, Carlo Briguori, MD, PhD, chief of the laboratory of interventional cardiology at Mediterranea Cardiocentro in Naples, Italy, said during a press conference at TCT 2019. Both groups continued the regimen for 4 hours after the procedure, he said.

The primary endpoint of contrast-induced acute kidney injury or acute pulmonary edema occurred in 5.7% of the device group and 10.3% of the LVEDP group (RR = 0.56; 95% CI, 0.39-0.79; number needed to treat to prevent one event = 22), Briguori said.

“The urine flow rate-guided approach carried out by the RenalGuard system seems to be superior to the left ventricular-end-diastolic-pressure-guided regimen to prevent the composite of acute kidney injury and acute pulmonary edema in high-risk patients,” he said at the press conference. “A strict control of potassium balance is required during RenalGuard therapy.”

CKD was defined as an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or less. High risk for acute kidney injury was defined as Mehran’s score of at least 11 and/or Gurm’s score of more than 7. The mean age in both groups was 74 years. The device group consisted of 66% men and the LVEDP group consisted of 59% men.

In a panel discussion at the press conference, experts debated different approaches to prevent contrast-induced acute kidney injury.

“I take a different approach; I think we should just get rid of contrast,” Gary S. Mintz, MD, senior medical adviser for the Cardiovascular Research Foundation, said. “Ziad Ali, MD, has pioneered the concept of zero-contrast PCI. More than 90% of planned zero-contrast PCIs never require even 1 cc of contrast during the procedure. They are totally imaging-guided. And if you get rid of contrast, you get rid of contrast nephropathy.” – by Erik Swain

Reference:

Briguori C, et al. Late-Breaking Trials 4. Presented at: TCT Scientific Symposium; Sept. 25-29, 2019; San Francisco.

Disclosures: Briguori reports no relevant financial disclosures. Mintz reports he received consultant fees/honoraria/speaker fees from Boston Scientific, Terumo and Volcano.

    Perspective
    Samir Kapadia

    Samir Kapadia

    The biggest take-home message is that the mechanism of protection related to hydration is not just how much you hydrate or how much you distend the vasculature, but how much urine flow you generate. Is it because you are dehydrated that the contrast is toxic to you, or is it because the urine flow through the kidney is not enough? Dehydration reduces urine flow, which leads to contrast-related problems, so to separate these two things is tricky.

    The researchers measured LVEDP, which is as close as you can get to proof about dehydration, because you are actually measuring the pressure, in one group, and in the second group, they aimed to increase the urinary flow and to match the hydration to urinary flow to keep it high. The latter strategy was relatively better. The primary endpoint was very generous, including all kinds of soft outcomes, such as serum creatinine increase of 25% or more than 0.5 mg/dL 48 hours from baseline. This is not related to need for dialysis or persistent kidney damage; it’s a rather small change in creatinine. The urinary-flow strategy was better in terms of being able to treat 22 patients to prevent one event.

    In my mind, we cannot definitively say that this strategy was extremely protective. What it tells clinicians is to pay attention to urinary flow in addition to hydration. Whether the system used in this trial played a key role is a commercial question. The academic question is whether the researchers reached the correct conclusion, which they did. The urine-flow strategy was better than the LVEDP strategy by the measures selected.

    Practice may change to some extent. If I had a high-risk patient, I would pay attention not just to whether the patient is hydrated, but what is their urine output. We suspected that, but now we have good proof from a randomized trial.

    Contrast-free procedures are possible in a very small number of patients. More realistically, we have been trying to reduce the contrast dose. There are now Bluetooth-derived systems that measure the contrast very carefully, so people are aware not to give too much dye. Totally contrast-free procedures are not going to happen routinely in the near future by any stretch of the imagination. Right now, contrast is necessary to see what we are doing.

    For any contrast-related procedure, doctors and patients should be very mindful of kidney-related issues, especially if contrast is injected intra-arterially. The best strategy is to minimize the dye.

    • Samir Kapadia, MD
    • Chairman
      Robert and Suzanne Tomsich Department of Cardiovascular Medicine
      Sydell and Arnold Miller Family Heart & Vascular Institute at Cleveland Clinic
      Professor of Medicine
      Cleveland Clinic Lerner College of Medicine of Case Western Reserve University

    Disclosures: Kapadia reports no relevant financial disclosures.

    See more from TCT