Investigators from the Renal Insufficiency Following Contrast Media Administration Trial II (REMEDIAL II; NCT01098032) report that the RenalGuard™ automated hydration matching system is safe and effective in preventing contrast-induced acute kidney injury (CI-AKI) in high- and very-high-risk patients with chronic kidney disease (CKD) compared with the optimal strategy of sodium bicarbonate infusion plus N-acetylcysteine (NAC). Carlo Brigouri, MD, PhD, Clinica Mediterranea, Naples, Italy, presented the findings.

Contrast-induced acute kidney injury is strongly associated with unfavorable early and late clinical outcomes in patients, which may be mitigated by maintaining a high urine flow. Prior strategies focused on forced diuretic regimens (typically with high-dose furosemide), which may be harmful due to a resulting negative fluid balance. The primary hypothesis of REMEDIAL II was that achieving a precise real-time high urine output and matched fluid balance using the RenalGuard™ hydration system would be noninferior to a control hydration strategy of prophylactic sodium bicarbonate plus NAC to prevent CI-AKI.

REMEDIAL II was a multicenter, prospective trial that included of 294 patients at elevated risk of contrast nephropathy, randomized to either hydration by the RenalGuard™ system (n=135; hydration with normal saline [target urine flow ≥300 ml/h]+1.5 g/L NAC+ 0.25 mg/kg furosemide) or hydration with sodium bicarbonate and acetylcysteine (n=145; hydration by 3 ml/kg of IV sodium bicarbonate for 1 hour before treatment and 1 ml/kg for 6 hours after, and 1200 mg NAC bid x 2 and 1.5 g during therapy). In all cases, the contrast media that was administered was iodixanol (an iso-osmolar, nonionic contrast agent).

The primary endpoint was the rate of CI-AKI, defined as an increase of ≥0.3 mg/dL in serum creatinine (sCr) concentration 48 hours after the procedure. Secondary endpoints included an increase in the sCr concentration ≥25% and ≥0.5 mg/dL at 48 hours after contrast exposure; changes in serum cystatin C (sCyC) concentration at 24 and 48 hours after contrast exposure; the rate of acute renal failure that required dialysis; the rate of in-hospital and 1-month major adverse events (composite of death, renal failure requiring dialysis, or acute pulmonary edema); and changes in serum and urine NGAL concentrations at 2, 6, 12, 24, and 48 hours postcontrast exposure.

The mean age of the 294 patients was 75 years, about one-third were women, almost all had hypertension, 70% had diabetes, half were on an ACE inhibitor, and the mean eGFR was 32 ml/min/1.73 m2. The mean volume of contrast that was infused was about 135–140 ml.

The percentage primary endpoint occurred in 11% in the RenalGuard™ group and 20.5% in the control group (OR, 0.47; 95% CI, 0.24 to 0.92; p=0.025; Figure 1). This translated into an absolute risk difference of 8.5%, or a number needed to treat of 12 to prevent 1 patient with a 10% rise in creatinine after contrast exposure. The secondary endpoint of an increase in the sCr concentration ≥25% at 48 hours after contrast exposure occurred in 2.7% in the RenalGuard™ group and 13% in the control group (p=0.001). Similarly, changes in creatinine and cystatin C at 48 hours (secondary endpoints) were significantly reduced (Table 1) in the RenalGuard™ group. At 1 month, 0.7% of patients in the RenalGuard™ group versus 4.8% in the control group needed dialysis (number needed to treat of 25 to prevent 1 patient requiring dialysis; p=0.031). The cumulative secondary endpoint of major adverse events occurred in 6.8% in the RenalGuard™ group compared with 9.6% in the control group (p=0.52)

Data from REMEDIAL II demonstrate that among patients who are at high risk for contrast nephropathy, the aggressive hydration and matched fluid balanced that were achieved with the RenalGuard™ system (in conjunction with NAC and furosemide) were superior to hydration with sodium bicarbonate plus NAC in preventing contrast-induced sCr increases. Future trials should determine whether the automated closed-loop system that balances fluid management could be replicated simply with a routine aggressive hydration strategy.