Hydrating TAVR patients via a system that matches diuretic-induced urine output with fluid intake confers greater protection against acute kidney injury (AKI) than does standard saline infusion, according to results of the randomized PROTECT-TAVI trial published online September 16, 2015, ahead of print in JACC: Cardiovascular Interventions.

Between February 2014 and January 2015, investigators led by Marco Barbanti, MD, of Ferrarotto Hospital (Catania, Italy), randomized 112 patients (mean age 80.6 years; 59.8% women) undergoing TAVR who were enrolled in their center’s REPLACE registry to hydration with the RenalGuard System (PLC Medical Systems; Milford, MA; n = 56) or standard saline solution (n = 56).

The RenalGuard strategy consisted of an initial bolus of 250 mL (150 mL if LVEF < 30%) of saline solution followed by furosemide-induced diuresis matched by IV saline infusion during the procedure and for 4 hours afterward.

Most patients received the self-expanding CoreValve device (Medtronic) or the balloon-expandable Sapien valve (Edwards Lifesciences), with the latter more often implanted in controls compared with the RenalGuard group (39.3% vs 17.8%; P = .021). The nonionic, iso-osmolar contrast agent iodixanol (Visipaque; GE Healthcare) was used in all patients, with no differences between the arms in terms of volume administered.

At baseline, an estimated glomerular filtration rate of less than 60 mL/min as calculated by the Cockcroft-Gault and the Modification of Diet in Renal Disease formulas was reported in 66.1% and 44.6% of patients, respectively. Overall, 57% of the cohort had moderate predicted risk of developing contrast-induced AKI based on a Mehran risk score of 11 to 16, with no differences between the study groups.

Device success was obtained in 95.5% of patients and at a similar frequency in both groups.

Varying degrees of AKI were defined according to Valve Academic Research Consortium Criteria as:

• stage 1: increase in serum creatinine (SCr) to 150% to 200% (1.5 to 2.0 × increase vs baseline) or increase of ≥ 0.3 mg/dL (≥ 26.4 mmol/L)
• stage 2: increase in SCr to 200% to 300% (2.0 to 3.0 × increase vs baseline)
• stage 3: increase in SCr to ≥ 300% (>3 × increase vs baseline) or SCr level of ≥ 4.0 mg/dL (≥ 354 mmol/L) with an acute increase of at least 0.5 mg/dL (44 mmol/L)

AKI Sharply Reduced

Incidence of AKI at 72 hours (primary endpoint) in the RenalGuard group was about one-quarter that in the control group (5.4% vs 25.2%; P = .014). Most cases were mild (stage 1). Severe AKI (stage 3) occurred in only 1 patient, who was in the control group, and none experienced in-hospital renal failure requiring dialysis. There was a correlation between the change in SCr value and the amount of dye used in the control group (P = .028) but not in the RenalGuard group (P = .570).

No significant hydration-associated complications were reported. The RenalGuard and saline-alone groups were similarly likely to develop asymptomatic hypokalemia (41.1% and 32.1%, respectively; P = .432), which was corrected with potassium supplementation. There was no difference in length of hospital stay between the arms.

At 30 days, rates of mortality, cerebrovascular events, bleeding, vascular complications, and rehospitalization for heart failure were low and similar between the groups.

On multivariable analysis, predictors of AKI risk were absence of RenalGuard use (OR 5.99; 95% CI 1.56-23.04) and AKI score of at least 4 (OR 4.31; 95% CI 1.39-13.37).

According to the authors, the results demonstrate that prophylactic use of RenalGuard in TAVR patients “is safe and superior to standard infusion of normal saline solution at a high dose.”

RenalGuard Makes Diuresis Safer

Despite data showing that postoperative AKI worsens the early and late prognosis of TAVR patients, “no standardized protocol for AKI prevention has been proposed yet,” they note. In general, the “cornerstone” of AKI prevention in patients exposed to contrast media is hydration, the authors write, and addition of furosemide may have both positive and negative effects. But the RenalGuard System “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,” they say, adding that this capability is especially important in TAVR patients, who typically have “labile hemodynamic compensation.”

Two randomized trials, REMEDIAL II and MYTHOS, have shown RenalGuard to be protective against AKI in patients undergoing PCI, the investigators recall, and now those findings have been extended to TAVR, with a 79% relative risk reduction in the RenalGuard group.

Acknowledging that this improvement did not translate into reductions in major clinical endpoints, they suggest that the reason may be the high prevalence of stage 1 AKI, which has been shown not to be associated with worse outcomes. “We can only speculate that [RenalGuard] also has the potential to reduce the risk of AKI stage 2 and 3,” the authors say. “To test this hypothesis, adequately powered studies targeting [such] patients… are warranted.”

Promising But Not Enough to Change Practice

In a telephone interview with TCTMD, Hitinder S. Gurm, MD, of the University of Michigan Health System (Ann Arbor, MI), called the study a “promising first step.” There was a clear reduction in AKI, but in such a small study a few cases going in a different direction could have changed the results, he pointed out.

Moreover, Dr. Gurm underlined the lack of effect on hard endpoints. “What we’re seeing is a change in a lab parameter, [and] what this means with respect to patient outcomes is unclear,” he said.

RenalGuard for TAVR is “worth looking into, but it is not [ready for] routine practice,” Dr. Gurm said, adding that he might consider it for “some extremely high-risk patients.” Even though the hydration strategy has generally been safe “in aortic stenosis patients with stiff ventricles, too much fluid can cause problems,” he explained, adding that the small risk of pulmonary edema calls for a cautious approach.

Dr. Gurm also observed that the reason patients experience AKI after TAVR remains unclear. “Part of it may be the contrast, and part of it may be patients’ hemodynamics,” he said. To the extent that contrast is the culprit, growing experience with TAVR is diminishing the risk, as clinicians have gotten better at selecting patients and planning the procedure, which has resulted in less need for imaging and lower contrast volume, he reported.

Dr. Gurm said he hopes that increasing use of TAVR would lead to more and larger studies evaluating accompanying hydration strategies. “We need more data to assess just what this level of AKI means in the long term.… Studies have shown that when you reduce AKI, that does translate into a reduction in events down the road. The hope would be that [RenalGuard] will do the same. But it’s too early to change clinical practice based on a surrogate endpoint.”

Source: 
Barbanti M, Gulino S, Capranzano P, et al. Acute kidney injury with the RenalGuard system in patients undergoing transcatheter aortic valve implantation: the PROTECT-TAVI trial. J Am Coll Cardiol Intv. 2015;Epub ahead of print.

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